Behaviors and Mental Disorders

All Conditions

Depression

Depressive Disorder

Affective Symptoms

Behavioral Symptoms

Patients assigned to the intervention arm will receive 3-6 CALM therapy sessions over 3-6 months delivered by a trained therapist at our center.

CALM

Gary Rodin

Sarah Hales

Chris Lo

Managing Cancer And Living Meaningfully (CALM) is a brief psychotherapy designed to alleviate distress in advanced cancer. In an earlier intervention-only pilot trial, CALM was associated with reductions in depressive symptoms and death anxiety and an increase in spiritual wellbeing. The purpose of this study is to assess the feasibility of a large-scale randomized controlled trial (RCT) of CALM and to identify preliminary effects in advanced cancer. This phase 2b pilot RCT employed intervention and usual care arms with 3 and 6 month follow-ups. The primary outcome was depressive symptoms (PHQ-9) and secondary outcomes included diagnosis of major depression (SCID), death anxiety, attachment security and spiritual wellbeing. Multilevel regression was used to compare change over time between groups. 60 patients with advanced cancer will be recruited from the Princess Margaret Cancer Centre, Toronto, Canada, and equally randomized into intervention and usual care conditions.

Abstract

Background Managing Cancer And Living Meaningfully (CALM) is a brief individual psychotherapy for patients with advanced cancer. In an intervention-only phase 2a trial, CALM showed promising results, leading to the present 2b pilot, which introduces procedures for randomisation and improved rigour in preparation for a phase 3 randomised controlled trial (RCT).

Aims To test trial methodology and assess feasibility of a confirmatory RCT.

Design A parallel-arm RCT (intervention vs usual care) with 3 and 6-month follow-ups. Assessment of feasibility included rates of consent, randomisation, attrition, intervention non-compliance and usual care contamination. Primary outcome: depressive symptoms (Patient Health Questionnaire-9; PHQ-9). Secondary outcomes: major depressive disorder (MDD), generalised anxiety, death anxiety, spiritual well-being, attachment anxiety and avoidance, self-esteem, experiential avoidance, quality of life and post-traumatic growth. Bayesian conjugate analysis was used in this low-powered setting.

Setting/participants 60 adult patients with advanced cancer from the Princess Margaret Cancer Centre.

Trial registration number NCT02353546.

http://dx.doi.org/10.1136/bmjspcare-2015-000866

CALM Phase 2b Pilot

Managing Cancer and Living Meaningfully (CALM): Phase 2b Pilot Randomized Psychotherapy Trial in Patients With Advanced Cancer

DSM: Diagnostic and Statistical Manual of Mental Disorders (APA, 2000)

Canadian Institutes of Health Research (CIHR)

University Health Network, Toronto

Neoplasms

Skin and Connective Tissue Diseases

Infections

Rare Diseases

Melanoma

Coxsackievirus Infections

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Dose of CAVATAK up to 3 x 10⁸ TCID50 for an additional 9 treatments at 3-week intervals

CVA21

This is an extended use study for patients who have received 10 doses of CAVATAK™ in the VLA 007 trial. There may be patients who have benefitted from the study drug and who might benefit from further treatment. In order to accommodate those patients further treatment to complete 48 weeks of CVA21 intratumoral injections will be made available.

CAVATAK in Patients With Stage IIIc or IV Malignant Melanoma to Extend Dosing to 48 Weeks (VLA-008 CALM Ext)

A Phase 2 Study of the Efficacy and Safety of Intratumoral CAVATAK™ (Coxsackievirus A21, CVA21) in Patients With Stage IIIc and Stage IV Malignant Melanoma to Extend Dosing for up to 48 Weeks Total (VLA-008 CALM Ext)

Participants with Grade 3 or Higher Adverse Events

Viralytics

Listed serious adverse events (SAEs) and adverse events (AEs) are irrespective of treatment relationship. No SAEs reported were attributable to CVA21. No serious unexpected adverse events (SUSARs) were reported for the study.

Dose of CVA21 up to 3 x 10⁸ TCID50 for an additional 9 treatments at 3-week intervals

Dose of CAVATAK up to 3 x 10⁸ TCID50 for an additional 9 treatments at 3-week intervals CVA21

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Mark Grose

Safety

Overall Study

Each patient will receive 4 separate Coxsackievirus A21 (CVA21) administrations in the first 8 days on trial (Days 1, 3, 5 and 8), followed by a fifth dose 2 weeks later (Day 22) and further administrations at 3 weekly intervals (Days 43, 64, 85, 106 and 127, up to a maximum of 10 sets of injections) until confirmed disease progression or development of excessive toxicity. Subjects with stable disease or better at Day 127 were eligible to receive up 9 more sets of CVA21 administrations under an extension protocol (VLA-008).

CVA21 is a live oncolytic virus preparation derived from the non-genetically altered prototype Kuykendall strain of Coxsackievirus A21.

Coxsackievirus A21 (CVA21)

Robert Andtbacka, MD

The purpose of this study is to assess the clinical efficacy of Intratumoral (IT) CVA21 in terms of immune-related Progression-Free Survival (irPFS) at 6 months as monitored via immune-related Response Criteria \[irRECIST 1.1\] (revised Response Evaluation Criteria In Solid Tumors \[RECIST\] 1.1).

This is a multicenter, open-label, 2-stage, single-arm efficacy and safety study. Approximately 63 patients with histologically proven stage IIIc or stage IV melanoma who fail to qualify for curative surgery and who bear one or more tumors that are accessible for direct injections and at least one measurable lesion by RECIST 1.1 criteria will be considered.

Prospective patients will attend the study center for initial screening within 28 days prior to treatment with CVA21. They will have the nature of the study and its procedures and risks fully explained. All patients must provide a written informed consent to participate in the study.

The dose of CVA21 for this study is 3 x 108 TCID50 (about 4.5 x 106 TCID50/kg for a 70-kg patient) by IT administration. Each patient will receive 4 separate CVA21 administrations in the first 8 days on trial (Days 1, 3, 5 and 8), followed by a fifth dose 2 weeks later (Day 22) and further administrations at 3 weekly intervals (Days 43, 64, 85, 106 and 127, up to a maximum of 10 sets of injections) or until confirmed disease progression or development of excessive toxicity.

Disease status will be assessed by contrast-enhanced computerized tomography (CT) or magnetic resonance imaging (MRI) scan and/or direct caliper measurement (and ultrasound assistance, if necessary) and categorized by immune-related RECIST 1.1 criteria prior to commencing treatment (baseline) and at Days 43, 85, 127 and 169 and 12-weekly intervals thereafter until disease progression. At 2 years, intervals can increase to 6 months.

At 12 weeks post-commencement of treatment (Day 85), if a patient's disease status is classed as progressive disease (but without rapid clinical deterioration) the patient may remain on the trial for a further 6 weeks, when his/her disease status will be confirmed prior to the scheduled treatment. If disease progression is confirmed, the patient will cease treatment but will remain on the study and be observed for efficacy and safety until initiation of treatment with non-CVA21 anticancer therapies. However, survival will be followed until death. If stable disease or better (CR or PR) is observed at this time, the patient will continue treatment as per the protocol. Complete and partial responses will be confirmed at the next contrast-enhanced CT or MRI scan analysis.

Patients who have evidence of biologic activity, i.e., tumor inflammatory reaction and/or stable disease or better, at 18 weeks (Day 127) are eligible to participate in the extension trial in which they will continue to receive IT injections of CVA21 every 3 weeks up to a total of 1 year of therapy from the first injection.

Throughout the trial, immunological responses to the tumor and CVA21 will be monitored.

After the full CVA21 injection schedule has been completed, patients will be followed at 12-weekly intervals beginning on Day 169 for a total of 12 months according to the schedule for safety assessment and indefinitely for survival. Patients with progressive disease (but without rapid clinical deterioration) at 6 months (Day 169) will have a further tumor assessment 6 weeks later for confirmation or continuation of observation for duration of disease control and all subjects will be followed for survival. Patients who are withdrawn from treatment with CVA21 during the treatment phase must also be followed up every 6 weeks for 12 weeks for safety and for survival.

A Study of Intratumoral CAVATAK™ in Patients With Stage IIIc and Stage IV Malignant Melanoma (VLA-007 CALM )

A Phase 2 Study of the Efficacy and Safety of Intratumoral CAVATAK™ (Coxsackievirus A21, CVA21) in Patients With Stage IIIc and Stage IV Malignant Melanoma (VLA-007 CALM )

To assess the clinical efficacy of Intratumoral (IT) CVA21 in terms of immune-related Progression-Free Survival (irPFS) at 6 months.

Per Immune-Related Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT/MRI or calipers: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Durable Response Rate (DRR) = CR + PR.

Listed SAEs and AEs are irrespective of treatment relationship. No SAEs reported were attributable to CVA21. No SUSARs were reported for the VLA-007/008 study.

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Height

Weight

Percentage of Participants With Immune-related Progression-Free Survival (irPFS) at 6 Months

Durable Response Rate

Anxiety Disorders

Quality of Life

Patients in the experimental group will receive the brief, individual, manualized CALM intervention, a semi-structured psychotherapy designed for patients with advanced cancer. CALM was developed based on empirical results, clinical observation and the theoretical foundations of supportive-expressive and existential approaches, as well psychodynamic and attachment theories. The sessions are delivered bimonthly over a period of 6 months. Sessions are reviewed to ensure treatment fidelity.

Supportive psycho-oncology intervention (SPI) includes counseling, psychoeducation and crisis intervention, which is the usual care intervention provided in our centres.

CALM intervention covers four domains, namely: 1) Symptom management and communication with health care providers; 2) Changes in self and relations with close others, 3) Spiritual well-being, sense of meaning and purpose, 4) Preparing for the future, sustaining hope and facing mortality

Active Comparator: Supportive psycho-oncology intervention Supportive psycho-oncology intervention (SPI) includes counseling, psychoeducation and crisis intervention, which is the usual care intervention provided in our centres.

Luigi Grassi, M.D.

Rosangela Caruso, M.D., PhD

Luigi Grassi, MD

Background: Patients with advanced cancer suffer from a variety of psycho-social symptoms that impair quality of life and may benefit from psychotherapeutic treatment. We describe here the methodology of a randomized controlled trial to test the effectiveness of a novel and brief semi-structured psychotherapeutic intervention, called Managing Cancer and Living Meaningfully (CALM), originally developed in Canada and now cross-culturally tested in Italy.

Methods/Design: The study is a single-blinded randomized controlled trial with 2 conditions: CALM intervention versus nonspecific supportive intervention (SPI) and assessments at baseline, 3 and 6 months. The coordinating site is the Program on Psycho-Oncology and Psychiatry in Palliative Care, University of Ferrara and Integrated Department of Mental Health, S. Anna University Hospital, in Ferrara, Italy. Another centre from northern and southern Italy will collaborate. Eligibility criteria include: ≥ 18 years of age; Italian fluency; no cognitive impairment; and diagnosis of advanced cancer. The intervention consists of 12 sessions , following the CALM manual and allowing for flexibility to meet individual patients' needs. It is delivered over a 6-month period and provides reflective space for patients (and their primary caregivers) to address 4 main domains: symptom management and communication with health care providers; changes in self and relations with close others; sense of meaning and purpose; and the future and mortality. The primary outcome is depression and the primary endpoint is at 6 months. Secondary outcomes include demoralization, generalized anxiety, death anxiety, spiritual well-being, quality of life, attachment security, posttraumatic growth, communication with partners, and satisfaction with clinical interactions.

Discussion: This trial is being conducted to determine the effectiveness of CALM in an Italian cancer setting. The intervention has potential cross-national relevance and, if shown to be effective, has the potential to be disseminated as a new approach in oncology to relieve distress and promote psychological well-being in patients with advanced cancer.

The study is coordinated by the Program on Psycho-Oncology and Palliative Care, University of Ferrara Northern Italy. Another centre from northern Italy will collaborate. The study is designed as a single-blinded randomized-controlled trial with two arms. Participants in the experimental group will receive the CALM intervention, while those in Control Group will receive a supportive intervention, which is usual psycho-oncology care in our settings.The primary outcome is depression. The primary endpoint is 6 months. Secondary outcomes include demoralization, generalized anxiety, death anxiety, spiritual well-being, quality of life, attachment security, posttraumatic growth, communication with partners, and satisfaction with clinical interactions.The study has received approval from Ethical Committees.

Interventions:Patients in the experimental group will receive the CALM intervention, a semi-structured psychotherapy designed for patients with advanced cancer. In this Italian adaptation, CALM consists of 12 individual sessions (45-60 minutes each), instead of the original 6 sessions. The sessions are delivered bimonthly over a period of 6 months.

The intervention covers four domains: 1) Symptom management and communication with health care providers; 2) Changes in self and relations with close others; 3) Spiritual well-being, sense of meaning and purpose; 4) Preparing for the future, sustaining hope and facing mortality.

Non-manualized supportive psycho-oncology intervention (SPI):The Control group intervention includes counseling, information, crisis intervention, which is the usual care intervention provided in our center. As with CALM patients, SPI patients receive up to twelve sessions of individual therapy during a period of 6 months.

Inclusion criteria are:18 years of age or more;fluency in Italian language; absence of cognitive deficit documented in the clinical records;diagnosis of "wet" stage IIIB or IV lung cancer; any stage of pancreatic cancer, stage III or IV ovarian and fallopian tube cancers, or other stage IV gynecological cancer; and stage IV breast, genitourinary, gastrointestinal, melanoma, sarcoma, or endocrine cancers (all with an expected survival of 12-18 months); a score ≥10 at the Patient Health Questionnaire and/or ≥ 20 at the Death and Dying Distress Scale. Exclusion criteria are: language barriers hindering psychotherapy;inability to commit to the required 12 sessions; concomitant psychotherapy.

Randomization procedure:Study participants are randomly assigned to receive either CALM or SPI. After obtaining informed consent , a research assistant includes patient's data on the random allocation list and informs the PI's about treatment allocation (CALM or SPI). The patient is not informed about treatment condition (CaLM or SPI).

Measures:The Patient Health Questionnaire (PHQ-9) is a 9-item measure of depression. It is composed by nine items, reflecting DSM-IV criteria for major depression. A four-point Likert scale scores from 0 (not at all) to 3 (nearly every day), with a cut-off score of ≥10 suggesting depression. For study purposes, two additional items assessing self-harm intention and rating how difficult these symptoms have made it to do lead one's life, have been included.The Demoralization Scale (DS) is a 24-item self-report tool assessing demoralization components of loss of meaning and purpose, dysphoria, disheartenment and helplessness. Items are scored on a five-point Likert scale ranging from 0 (never) to 4 (all the time). Low levels of demoralization were indicated by a score 10, moderate demoralization by a score 11-36, and high demoralization by a score \> 37.The Generalized Anxiety Disorder Questionnaire (GAD-7) is a 7-item self-report instrument screening the severity of GAD symptoms. Items are scored on a four-point Likert scale ranging from 0 (not at all) to 3 (nearly every day). Scores ≤4 indicate absence of anxiety, scores from 5 to 9 suggest that mild anxiety is present, and scores from 10 to 15 indicate moderate levels of anxiety. An eighth item rating how difficult these symptoms have made it to lead one's daily life has been included. The Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale (FACIT-SP)\[v\] is a 12-item self-report tool, exploring spiritual well-being, in terms of sense of meaning, faith and inner peace. Items are scored on a five-point Likert scale from 0 (not at all) to 4 (very much), with higher scores indicating a greater spiritual wellbeing.The Posttraumatic Growth Inventory (PTGI) is a 21-item self-report measure of positive psychological changes after traumatic events. It consists of four subscales: New Possibilities, Appreciation of Life, Relating to Others and Spiritual Change. Items are scored on a three-point Likert scale ranging from 0 (not at all) to 2 (very much) with higher scores indicating greater post-traumatic growth.The Quality of Life at the End of Life-Cancer Scale (QUAL-EC) is a self- report measure of quality of life in patients near the end of life. It originally consists of four subscales: Symptom Control, Relationship with Health Care Providers, Preparation for End of Life and Life Completion. For this study purposes, the symptom control subscale is not included, thus only items 4-17 are used. Items are scored on a five-point Likert scale ranging from 1 (not at all) to 5 (completely), with higher scores indicating higher quality of life.The Death and Dying Distress Scale (DADDS), is a 15-item self-report measure assessing specific concerns of advanced cancer patients about end of life, feeling a burden to others and wasted opportunities. It is scored on a six-point Likert scale from 0 (no distress) to 5 (very much distress), with higher scores indicating higher death anxiety and distress.The Experiences in Close Relationships Inventory Modified Short Form Version (ECR-M16), is used in its 16-item self-report form to measure the attachment style. The scale yields scores on two dimensions of attachment: avoidance and anxiety. Items are scored on a seven-point Likert scale ranging from 1 (disagree) to 7 (agree), with a total sum score on each subscale ranging from 16 to 56. Higher scores on both subscales indicate higher attachment insecurity.The Memorial Symptom Assessment Scale (MSAS) \[x\]assesses the disease symptom severity. The scale, in its shortened version (MSAS- short form), measures the presence and severity of 28 common physical symptoms of cancer. Items are scored on a five-point Likert scale ranging from 0 (not at all) to 4 (very much).

The Couple Communication Scale (CCS) is used for participants who have a partner. The 10-item CCS taken from the PREPARE/ENRICH Inventory is concerned with an individual's feelings, beliefs, and attitudes about the communication in his/her romantic relationship. Each item is scored from 1 (strongly disagree) to 5 (strongly agree).

Intervention and control participants will complete the Clinical Evaluation Questionnaire (CEQ) at 3 and 6-months. The CEQ is a seven-item self-report questionnaire which assesses the amount of clinical benefit patients have experienced by from therapy at the time of the assessment. Items are rated from 0 to 4, with 0 (no clinical benefit) and 4 (a great clinical benefit).Satisfaction of patients will also be qualitatively assessed by inviting them to share comments in a written form after completing CEQ questionnaire.

Assessment:At baseline (T0), participants provide demographics and medical and treatment data using a standardized questionnaire and will complete all outcome measures, with the exception of the CEQ. The PHQ-9 and DADDS are first administered to assess eligibility prior to study entry, followed by the remaining baseline outcomes. Follow-up assessments on all outcomes are collected at three months (T1) and six months (T2). The CEQ is administered only at three months (T1) and six months (T2) as it is an evaluation of the intervention received to date. At T2, participants will also be queried about their having remained blind (or not) to randomization.

Statistical methods:To calculate the required sample size, we used a validated, manualized online power and sample size calculator that is ideal for longitudinal multilevel designs, GLIMMPSE \[ \]. A total sample size estimate for our primary hypothesis, that the treatment group (CALM) will demonstrate a greater higher improvement ind depressive symptoms (PHQ-9) at follow-up periods, as compared to the control group (SPI), was derived with a target power of 80% and alpha of .05 and with estimated mean scores, with variability, and cross-time correlations entered. For the primary hypothesis, the calculated total sample size is 124 patients (62 patients per treatment arm). To account for anticipated attrition while maintaining the targeted power, we used the following equation to calculated an adjusted sample size: N = N0 \* (1 + DRP), where N0 = original estimated sample size required at baseline; DRP = anticipated dropout rate across participants. For an anticipated completion rate of 70% rate (30% dropout rate), the adjusted sample size for this attrition rate is N = 124 \* (1 + .30) = 161.2. The adjusted sample size at baseline will therefore be 162, with 81 patients per treatment arm.

Statistical analyses will be carried out by using SPSS Statistics program. For the final analyses we will use an intention-to-treat approach (ITT) and compare patients in the assigned treatment arms. To test the pPrimary hypothesis : we hypothesize that mean depression scores in the intervention arm will be lower than in the control arm at 3 and 6 months, . We will use multilevel modeling (MLM) with maximum likelihood estimation to conduct the intent-to-treat analysis in testing hypotheses. MLM includes all participants, including those with missing data, in model estimation and also accounts for both inter-center and intra-center variability.To test for treatment-arm differences, we will compare the CALM and SPI groups on the primary outcome of PHQ-9 scores and on the secondary outcomes at the follow-up periods. This will entail the following set of MLM analyses:i)We will first test the level-1 predictor of Time, coded for the primary hypothesis as a categorical variable representing baseline and the 6-month follow-up period (primary endpoint). To code time for tests of secondary hypotheses, the categorical time variable will include baseline and the 3-month (secondary endpoint) and 6-month follow-up periods. ii)Next, we will add the level-2 treatment-group main effect and the cross-level treatment group x time interactions to test the hypothesized treatment-group differences at follow-up periods. Pairwise comparisons will evaluate the treatment-group difference at each follow-up period.iii)We will finally test whether the fixed effects in step ii change when any identified covariates are added to control for their effects. As a sensitivity analysis, we will use multiple imputation to examine the influence of missing values. Lastly, prior trial results suggest that there may be arm differences in the processing of death-related distress such that individuals with moderate death anxiety tend to be more responsive to the intervention than either those with low death anxiety (approximately the lower third of the distribution) or those with high death anxiety (the upper third). We will conduct a sub-analysis to confirm this effect, by examining the effect of removing individuals with low and high death anxiety scores at baseline (i.e., DADDS \< 15), following the Canadian protocol.

We will also qualitatively analyze the participants' comments about CALM and SPI on the CEQ. NVivo Plus software package will be used for the qualitative analysis of data.

Managing Cancer and Living Meaningfully (CALM) Adapted to Italian Cancer Care Setting

Effectiveness of a Brief Manualized Intervention Managing Cancer and Living Meaningfully (CALM) Adapted to the Italian Cancer Care Setting. Study Protocol for a Randomized Controlled Trial

The Patient Health Questionnaire (PHQ-9) is a 9-item measure of depression. It is composed by nine items, reflecting Diagnostic and Statistical Manual-IV criteria for major depression. A four-point Likert scale scores from 0 (not at all) to 3 (nearly every day), with a total score ranging from 0 to 27. A cut-off point of ≥10 is used as recommended for the screening of depression,but further analysis will be done according to other cut-off scores recommended to classify the type of depression, specifically, no depression/minimal (score 0-4), mild depression (score 5-9), moderate depression (score10-14), moderately severe depression (score 15-19), severe depression (score 20-27). For study purposes, two additional items assessing intent to cause self-harm and rating how difficult these symptoms have made it to do work, take care of things at home, or get along with other people, have been included.

The Generalized Anxiety Disorder Questionnaire (GAD-7)is a 7-item self-report measure designed to screen the severity of GAD symptoms. Items are scored on a four-point Likert scale ranging from 0 (not at all) to 3 (nearly every day) with a total score ranging from 0 to 21. Scores up to 4 indicate absence of anxiety, scores from 5 to 9 indicate the presence of mild anxiety, scores from 10 to 15 indicate moderate anxiety. An eighth item rating how difficult these symptoms have made it to do work, take care of choirs at home, or get along with other people, has been included.

The Death and Dying Distress Scale (DADDS) is a 15-item self-report measure assessing specific concerns of advanced cancer patients about end of life, feeling a burden to others and wasted opportunities. It is scored on a six-point Likert scale from 0 (no distress) to 5 (very much distress), with a total score ranging from 0 to 75, a greater score indicating higher death anxiety and distress.

The Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale (FACIT-SP) is a 12-item self-report measure of spiritual well-being, assessing patients' sense of meaning, peace and faith. Items are scored on a five-point Likert scale from 0 (not at all) to 4 (very much), with a total score ranging from 0 to 48, with higher scores indicating higher spiritual wellbeing.

The Quality of Life at the End of Life-Cancer Scale (QUAL-EC)is a self- report measure of quality of life in patients near the end of life. It originally consists of five subscales: symptom control, relationship with health care providers, preparation for end of life and life completion. For this study purposes, the symptom control subscale is not included, thus only items 4-17 are used assessing the remaining subscales. Items are scored on a five-point Likert scale ranging from 1 (not at all) to 5 (completely), with a total score ranging from 14 to 70 and higher scores indicating higher quality of life.

The Experiences in Close Relationships Inventory Modified Short Form Version (ECR-M16), is used in its 16-item self-report form to measure the attachment style (i.e. style in relationships perceived to be important for felt security). The scale yields scores on two dimensions: avoidance and anxiety. Items are scored on a seven-point Likert scale ranging from 1 (disagree) to 7 (agree), with a total sum score ranging from 16 to 56 on each subscale. Higher scores on one or both subscale indicate higher attachment insecurity.

The Posttraumatic Growth Inventory (PTGI) is a 21-item self-report scale which measures positive psychological changes after trauma. It consists of four subscales: new possibilities, appreciation of life, relating to others and spiritual change. Items are scored on a three-point Likert scale ranging from 0 (not at all) to 2 (very much) with a total score ranging from 0 to 42. High scores indicate greater post-traumatic growth.

The Couple Communication Scale (CCS) is used for participants who are married, common-law, or in a long-term relationship. The CCS is taken from the PREPARE/ENRICH Inventory, of which we used ten items concerning romantic relationship, with each item scored from 1 (strongly disagree) to 5 (strongly agree).

Intervention and control participants complete respectively the Clinical Evaluation Questionnaire (CEQ) \[19\] - CALM and SPI at 3 and 6-months; a seven-item self-report questionnaire which assesses the level of mastery and insight patients have gained in time and the extent to which therapeutic sessions were perceived as helpful for patients. Experimental group patients' satisfaction will also be qualitatively assessed by inviting participants to share comments in a written form after completing CEQ questionnaire.

Princess Margaret Hospital, Canada

Università degli Studi di Ferrara

Professor and Chair of Psychiatry

Symptoms and General Pathology

Neoplasm Metastasis

Psychotropic Drugs

All Drugs and Chemicals

Usual care includes routine screening for depression and other distress in oncology outpatient clinics, communication of screening information to the medical treatment team, and referral as needed.

Gary Rodin, MD

Sarah Hales, MD, PhD

Chris Lo, PhD

The purpose of this study is to test the effectiveness of a brief manualized individual psychotherapy, called Managing Cancer and Living Meaningfully (CALM), to reduce distress and promote psychological well-being in patients with various types of cancer, including metastatic disease.

We have developed and pilot-tested a brief manualized individual psychotherapy, called Managing Cancer and Living Meaningfully (CALM), to reduce distress in patients with various types of cancer, including metastatic disease. We propose to conduct a two-arm randomized controlled trial (RCT) to test the effectiveness of CALM against usual care (UC) for the reduction of distress in patients with various types of cancer, including metastatic disease. Usual care at our center includes routine screening for depression and other distress in oncology outpatient clinics, communication of screening information to the medical treatment team, and referral as needed for non-standardized, and primarily instrumental, psychosocial care and psychiatric assessment and treatment.

The design will be an unblinded RCT consisting of two conditions (CALM and UC), with a baseline assessment and follow-ups at three and six months. The trial will take place in Princess Margaret Cancer Centre, University Health Network, a comprehensive cancer center in Toronto, Canada. Participants will be outpatients with various types of cancer, including metastatic disease.

Managing Cancer and Living Meaningfully (CALM): A Study to Evaluate the Effectiveness of a Psychological Intervention for Cancer Patients

Managing Cancer and Living Meaningfully (CALM): A Randomized Controlled Trial of a Psychotherapeutic Intervention for Patients With Metastatic Cancer

A reliable and valid 9-item measure of depression that has been used widely with advanced cancer patients.

A semi-structured interview that allows researchers to make clinical diagnoses according to DSM criteria. Portions of the Mood Disorders and Optional Disorders modules will be administered: major depressive episode and minor depressive disorder.

A widely used and validated 7-item self-report measure designed to screen and assess the severity of GAD symptoms.

A 12-item self-report measure of spiritual well-being, assessing spiritual meaning and peace, and faith, that has been widely used in palliative care research.

A 21-item self-report scale that measures positive psychological changes after trauma. It has been used as a measure of psychological growth in cancer and as an outcome measure for intervention studies.

A measure of quality of life in patient populations near the end of life.

A recently developed, 15-item measure assessing death anxiety in patients with advanced cancer.

A 24-item self-report measure that assesses one aspect of existential distress, which includes loss of meaning and purpose, disheartenment and helplessness.

A 16-item self-report measure of attachment security.

A measure for participants who are married, common-law, or in a long-term relationship. This measure is concerned with an individual's feelings, beliefs, and attitudes about the communication in his/her relationship.

A 7-item measure evaluating the extent to which patients felt emotionally supported by the clinical services provided.

Nervous System Diseases

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Inform CALM adaptations for caregivers of patients with brain cancer.

The CALM intervention includes 3 to 6 individual therapy Zoom teletherapy sessions, each approximately 50-60 minutes in length biweekly, delivered over 3 months. Participants (caregivers) will be asked to complete self-report surveys of behavioral and psychological variables surveys at the following timepoints:

Within one week before initiating the CALM intervention therapy (baseline) and immediately after the program (post-intervention)

In addition, after each intervention session, participants will complete a brief post-session survey to assess acceptability of CALM session components.

Lastly, participants will complete an exit interview immediately following the end of the intervention.

CALM Therapy

Ashlee R Loughan, PhD

To conduct a mixed-method Phase Ia Define Trial of caregivers' participation in CALM therapy with post-session surveys and individual exit interviews in order to evaluate suitability and adapt the CALM intervention to the needs of caregivers in neuro-oncology.

Exploring caregivers' experiences of CALM intervention will inform more effective, targeted, supportive care for this traditionally underserved group in need of emotional support. We will use the data from this study to adapt the CALM intervention to the specific needs of caregivers in neuro-oncology

This study has been designed in accordance with the NIH Science of Behavior Change ORBIT model for developing behavioral interventions and represents a Phase Ia Define Trial.

Forgotten Voices: Addressing Unmet Needs in Brain Tumor Caregivers

Forgotten Voices: Addressing Unmet Needs in Brain Tumor Caregivers (AIM 2)

Utilizing post-session surveys, determine caregiver satisfaction (5-point Likert Scale) with 1) topic applicability; 2) perceived benefit of session; 3) comfort with interventionist(s); 4) overall satisfaction and 5) likelihood of recommending the program to others. Higher scores represent greater caregiver satisfaction with the CALM intervention.

Caregivers will be asked a number of open-ended questions about their recommendations to CALM during a semi-structured exit interview. Exit interviews will be audio recorded and transcribed verbatim. A co- investigator and a second independent coder will separately review each transcript to identify common themes and develop a coding framework of free responses. All results will be reviewed for agreement and comparison to the raw data, and discrepancies will be resolved through discussion with the PI until reliability is reached (Kappa\>.80).

American Psychological Foundation

Virginia Commonwealth University

Respiratory Tract (Lung and Bronchial) Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Lung Neoplasms

Breast Neoplasms

Carcinoma, Renal Cell

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

CALM optimally consists of six individual sessions of 45 to 60 minutes, delivered over a three- to six-month period. CALM sessions address four broad and interrelated domains found to be important and relevant in this population: (1) symptom management and communication with healthcare providers, (2) changes in personal relationships, (3) sense of meaning and purpose, and (4) the future, hope and mortality.

Treatment as usual (TAU) for managing distress in brain cancer involves being provided a list of local / national resources (e.g., psychologist, social worker, or other mental health providers) if an individual chooses to seek treatment for the distress they are experiencing.

The CALM intervention is a supportive-expressive therapy that is administered by CALM trained clinicians in a particular style.

Treatment as usual includes a list of local / national resources (e.g., psychologist, social worker, or other mental health providers) if an individual chooses to seek treatment for the distress they are experiencing.

Treatment as usual

Giuliana Zarrella

Ashlee Loughan, Ph.D

Ashlee Loughan, Ph,D

The purpose of this study is to test an empirically supported psychotherapeutic intervention, Managing Cancer and Living Meaningfully (CALM), compared to treatment as usual (TAU) in those with malignant brain cancer diagnoses.

CALM: Managing Distress in Malignant Brain Cancer

Managing Distress in Malignant Brain Cancer - Phase IIc RCT

Percent of interested individuals who undergo screening

Percent of eligible individuals who consent to the trial

Percent of consented individuals who complete the CALM intervention

Percent of consented individuals who complete post-intervention questionnaires

Percent of consented individuals who complete follow-up questionnaires

Satisfaction ratings from participants during exit interview (e.g., Rate your overall benefit on a scale of 1-5).

Percent of participants who would recommendation CALM to others will be assessed during the exit interview (e.g., Would you recommend this program to others?)

Spots Global Cancer Trial Database for calm

Every month we try and update this database with for calm cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
CALM Phase 2b Pilot	NCT02353546	Depression	CALM	18 Years -	University Health Network, Toronto
CAVATAK in Patients With Stage IIIc or IV Malignant Melanoma to Extend Dosing to 48 Weeks (VLA-008 CALM Ext)	NCT01636882	Melanoma	CVA21	18 Years -	Viralytics
A Study of Intratumoral CAVATAK™ in Patients With Stage IIIc and Stage IV Malignant Melanoma (VLA-007 CALM )	NCT01227551	Malignant Melan...	Coxsackievirus ...	18 Years -	Viralytics
Managing Cancer and Living Meaningfully (CALM) Adapted to Italian Cancer Care Setting	NCT03068013	Depression Anxiety Quality of Life	CALM SPI	18 Years -	Università degli Studi di Ferrara
Managing Cancer and Living Meaningfully (CALM): A Study to Evaluate the Effectiveness of a Psychological Intervention for Cancer Patients	NCT01506492	Depression	CALM	18 Years -	University Health Network, Toronto
Forgotten Voices: Addressing Unmet Needs in Brain Tumor Caregivers	NCT05590273	Caregivers Neuro-Oncology Brain Cancer	CALM Therapy	18 Years -	Virginia Commonwealth University
CALM: Managing Distress in Malignant Brain Cancer	NCT06180460	Brain Tumor Brain Metastase... Brain Cancer Metastatic Lung... Metastatic Brea... Metastatic Mela... Metastatic Colo... Metastatic Kidn...	CALM Treatment as us...	18 Years -	Virginia Commonwealth University

Spots Global Cancer Trial Database for calm

Every month we try and update this database with for calm cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for calm cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.