Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Recurrence

Endometrial Neoplasms

Disease Attributes

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Bone Density Conservation Agents

Antineoplastic Agents

All Drugs and Chemicals

Tamoxifen

Aromatase Inhibitors

Progesterone

Antineoplastic Agents, Hormonal

Progestins

Hormones

Hormone Antagonists

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Selective Estrogen Receptor Modulators

Estrogen Receptor Modulators

Enzyme Inhibitors

Patients with advanced stage or recurrent endometrial cancer treated with hormonal therapy

Hormonal therapy used for treatment in endometrial cancer patients

Hormonal Antineoplastics

Maartje Luijten, MD

Hanny Pijnenborg, MD PhD

Maartje Luijten

Hanny Pijnenborg

Roy Lalisang, MD PhD prof

Andrea Romano, MD PhD

Willem Jan Van Weelden, MD

The PROMOTE study aims at optimising use of hormonal therapy in advanced stage and recurrent endometrial cancer analysing tumor tissue taken before start of hormonal therapy

There is limited consensus about the position of hormonal treatment in advanced and metastatic endometrial carcinoma (EC). This is due to lack of good quality data on patient selection, and predictive biomarkers. Consequently, consideration of hormonal therapy is subjected to personal experience of the treating physician, rather than on refined clinical and up-to-date molecular criteria. Hormonal therapy has limited side-effects, and is better tolerated than systematic chemotherapy. Since EC patients are often elderly women with comorbidities, more effective and less aggressive treatment options are needed, underlining the urgency of an explorative study on this topic.

Endometrial cancer is the most common malignancy of the female genital tract in developed countries, with increasing incidence due to obesity and increased life expectancy. Most patients are diagnosed at an early stage, and have a favourable prognosis with surgery alone. Yet, 20% of the patients present with advanced or metastatic EC and have a poor outcome even with systemic treatment. Response rate of chemotherapy in advanced or metastatic EC is 30-60%, dependent of previous chemotherapy, with a progression free survival (PFS) of 3-14 months and 40% treatment related morbidity. In comparison, response to hormonal therapy is 20%-40%, with side effects in less than 5%. The overall PFS is 3 months, yet for those who respond the PFS can be up to several years.

To improve selective use of hormonal therapy in EC by evaluating applied hormonal therapy in advanced and metastatic EC and correlate response to molecular tumour analysis and translate this knowledge after validation into clinical practice

Tumor samples originating from before start of hormonal therapy

PROMOTE Study: Prediction of Response Of HorMOnal Treatment in Advanced and Recurrent Endometrial Cancer

Complete or partial response according to RECIST criteria

Interval from start of hormonal therapy to progressive disease or death

Complete or partial response or stable disease according to RECIST criteria

Health-related quality of life during hormonal therapy as tested with the validated EORTC-QLQ-C30 and EORTC-QLQ-EN24 quality-of-life scales at start of hormonal therapy and 6 months after start therapy

Haukeland University Hospital

Maastricht University Medical Center

Brno University Hospital

Holycross Cancer Center Kielce

Medical University of Lublin

Hospital del Mar

Hospital Vall d'Hebron

Royal Cornwall Hospitals Trust

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

The Netherlands Cancer Institute

Canisius-Wilhelmina Hospital

Catharina Ziekenhuis Eindhoven

Erasmus Medical Center

Leiden University Medical Center

Radboud University Medical Center

Skin and Connective Tissue Diseases

Gland and Hormone Related Diseases

Rare Diseases

Breast Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Uterine Cervical Neoplasms

Vaginal Neoplasms

Vulvar Neoplasms

Carcinoma

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Uterine Cervical Diseases

Vulvar Diseases

Vaginal Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Vaginal Cancer

Vulvar Cancer

Participants randomized to the intervention will receive the Strong Together serious game program on a tablet computer. The goal of this serious game is to teach the participant how to advocate for her needs relate to her cancer and treatment. The research team will send participants weekly notifications for 12 weeks to alert them that a new serious game session is available and encourage them to complete one session per week.

If randomized to the enhanced care as usual arm, the research team will give participants a paper-based self-advocacy patient brochure published by the National Coalition for Cancer Survivorship. This guide is not a part of usual care, but is freely available on the Internet.

The Strong Together serious game program is an interactive, immersive education program in which participants quickly learn the behaviors of self-advocacy and the potential consequences of self-advocating or not. Participants will receive weekly game sessions to play at home for three months.

Strong Together serious game

Teresa H Thomas, PhD, RN

Self-advocacy, defined as the ability of a patient to get her needs and priorities met in the face of a challenge, is an essential skill but not all women with advanced cancer are able to do it. We want to instruct women with advanced cancer who have low self-advocacy to self-advocate for their health and well-being. We will test a new "serious game" or video program that teaches self-advocacy skills through interactive, situation-based activities. The goal of the Strong Together serious game is to engage participants in challenges commonly experienced by women with advanced cancer, offer them choices to self-advocate or not, and directly show them the health and social benefits of self-advocating and the negative consequences of not self-advocating. Through engaging in the Strong Together program, participants vicariously learn the essential skills of self-advocacy, understand the downstream effects of using or not using these skills, and learn distinct behaviors that they can then use to address their own challenges.

Background: When faced with the challenges of advanced cancer, women must advocate (or stand up) for their needs and priorities. However, there are no interventions to promote self-advocacy among female patients with advanced cancer. Preliminary work has developed a theoretically-based, psychometrically-strong measure of self-advocacy (the Female Self-Advocacy in Cancer Survivorship (FSACS) Scale) and demonstrated correlations with symptom burden and healthcare utilization. Serious games offer a novel mechanism by which to deliver interactive, engaging health education that links users' choices to consequences so that users learn a desired skill. The fully-automated Strong Together self-advocacy serious game may allow women with advanced cancer to learn self-advocacy skills and therefore improve their health outcomes.

Objective/Hypothesis: The purpose of this pilot randomized controlled trial (RCT) is to evaluate the feasibility, acceptably, and preliminary efficacy of the Strong Together serious game.

Specific Aims:

Specific Aim 1: To evaluate the feasibility and acceptability of the 3-month Strong Together intervention.

* Benchmark 1: At least 75% of participants will engage in at least 8 out of the 12 serious game sessions.
* Benchmark 2: At least 80% of participants will find the intervention acceptable based on ratings of perceived satisfaction and ease of use, as well as feedback from qualitative exit interviews.

Specific Aim 2: To explore the differences in self-advocacy and symptom burden between groups over time.

• Research Question: Do patients who receive the intervention report improved self-advocacy and lower symptom burden compared to those assigned to enhanced care as usual?

Study Design: This pilot RCT will recruit (N=84) women from cancer clinics at the University of Pittsburgh Medical Center. Eligibility criteria include: female; age ≥ 18 years; diagnosis of Stage III or IV gynecological or Stage IV breast cancer within the past 3 months; 6-month prognosis; Eastern Cooperative Oncology Group score of 0-1; and ability to read and write in English. Measures will be collected at baseline, 3 months, and 6 months. Randomization (2:1) will occur to the 3-month Strong Together intervention group or the enhanced care as usual group. Feasibility will be assessed by calculating percentages of the intervention's dosage, engagement, recruitment, retention, and data completion. Acceptability will be assessed through exit interviews and an acceptability scale. Preliminary efficacy will be measured by exploring differences in self-advocacy and symptom burden scores and calculating point and interval estimates between the groups at 3 and 6 months.

Cancer Relevance: This study represents a unique opportunity to address the lack of self-advocacy interventions, reduce the risks of women with low self-advocacy, and guide an adequately-powered RCT to educate women with advanced cancer to self-advocate.

Inclusion criteria are based on cancer diagnoses which primarily occur in women (gynecological and breast cancer).

Self-Advocacy Serious Game in Advanced Cancer

Piloting a Serious Game to Improve Self-Advocacy Among Women With Advanced Cancer

We will calculate the number of participants in the intervention group who complete two-thirds (66.7%) of the intervention sessions as a measure of intervention feasibility. We will accept that we achieved adequate feasibility if at least 75% of participants engage in at least eight out of the twelve serious game sessions.

We will accept that we achieved adequate acceptability if at least 80% of participants find the intervention acceptable based on the Post Study System Usability Questionnaire scores and if no issues are raised during the qualitative interviews and feedback that cannot be revised prior to the future trial.

We anticipate that self-advocacy scores will increase (improve) among participants in the intervention group compared to the enhanced care as usual group.

We anticipate that symptom burden scores will decrease (improve) among participants in the intervention group compared to the enhanced care as usual group.

We anticipate that the frequency of healthcare utilization will decrease (improve) among participants in the intervention group compared to the enhanced care as usual group.

We anticipate that quality of life will increase (improve) among participants in the intervention group compared to the enhanced care as usual group.

University of Pittsburgh

Assistant Professor

Nervous System Diseases

Peripheral Nervous System Diseases

Head and Neck Neoplasms

Neuromuscular Diseases

Micronutrients

Vasodilator Agents

Lipid Regulating Agents

Hematinics

Vitamins

Paclitaxel

Albumin-Bound Paclitaxel

Niacinamide

Niacin

Nicotinic Acids

Folic Acid

Vitamin B Complex

Trace Elements

Hypolipidemic Agents

Antimetabolites

Nicotinamide

Nicotinic Acid

Vitamin B3

Folate

Vitamin B9

Daily oral administration of nicotinamide riboside 300 mg (150 mg a.m. and p.m.) for one week with dose escalation to 1000 mg (500 mg a.m. and p.m.) for remaining 11 weeks.

Nicotinamide Riboside

Donna L Hammond, PhD

Alexandra Thomas, MD

The purpose of this single-arm phase II trial is to determine whether nicotinamide riboside (NIAGEN®) prevents the progression of peripheral sensory neuropathy in patients receiving infusions of paclitaxel or nab-paclitaxel for the treatment of metastatic breast cancer or recurrent platinum-resistant ovarian, endometrial, peritoneal, fallopian tube cancer or metastatic head and neck cancer.

Peripheral neuropathies are a dose-limiting, disabling, and debilitating side effect of virtually every known class of chemotherapeutic agent, and are referred to as chemotherapy-induced peripheral neuropathies (CIPN) (Seretny et al., 2014). The incidence and severity of CIPN increase as the cumulative dose, frequency of administration, and the number of therapeutic cycles increase. As many as 68% of patients have CIPN when assessed within 30 days of completing treatment. Patients experience paresthesias, dysesthesias (an unpleasant abnormal sensation, whether spontaneous or evoked), hyperalgesia (increased pain from a stimulus that normally provokes pain), allodynia (pain due to a stimulus that does not normally provoke pain), numbness or loss of sensation, or ongoing pain that is burning, lancinating or electric shock-like in nature. CIPN can seriously diminish a patient's quality of life, and can interfere with self-care and activities of daily living. The severity of CIPN may also necessitate reducing the dose of chemotherapeutic agent, delaying the next cycle of chemotherapy, or terminating treatment entirely (Argyriou et al., 2012; Argyriou et al., 2014; Miltenburg et al., 2014; Park et al., 2013).

Nicotinamide adenine dinucleotide (NAD+) is an essential redox coenzyme required for cell viability, basic bioenergetics, and fast axonal transport (Yang and Sauve, 2016). It plays an important role in protection against axonal injury from either mechanical or neurotoxic injury (Araki et al., 2004; Sasaki et al., 2006; Sasaki et al., 2009; Gerdts et al., 2015; Khan et al., 2014; Conforti et al., 2014; Di Stefano et al., 2015). Nicotinamide riboside (NIAGEN®) is a form of vitamin B3 and a precursor in the pathway for synthesis of NAD+ (Bieganowski et al., 2004; Trammell et al., 2016; Chi and Sauve, 2013). Oral administration of NIAGEN® increases levels of NAD+ in the blood, liver, skeletal muscle, and other tissues (Canto et al., 2012; Hamity et al, 2017; Airhart et al., 2017; Martens et al., 2018).

NIAGEN®) has been reported to prevent tactile hypersensitivity and blunt the affective dimension of nociception in a rat model of CIPN (Hamity et al., 2017) It also prevents signs of peripheral neuropathy in a mouse model of diabetes (Trammell et al., 2016) The proposed single-arm pilot phase II study will examine whether daily dosing with NIAGEN®) can prevent the progression of CIPN in persons with stage IV breast cancer or recurrent platinum-resistant ovarian, endometrial, peritoneal, or fallopian tube cancer receiving once weekly infusions of paclitaxel for 12 weeks.

In this study, persons with metastatic breast cancer, platinum-resistant recurrent ovarian, peritoneal, endometrial, or fallopian tube cancer, or platinum-resistant recurrent or metastatic head and neck cancer who are receiving weekly infusions of paclitaxel or nab-paclitaxel and anticipated to survive for at least 3 months will be offered the opportunity to enroll in this study when they develop a peripheral neuropathy of at least grade 1. Persons with peripheral neuropathy of no greater than a grade 2 from prior therapy may also enroll in this study if they are receiving weekly infusions of paclitaxel or nab-paclitaxel. Upon enrollment, health care providers will review the overall severity of the participant's neuropathy and assign a baseline grade. Participants will also complete two short questionnaires that will more specifically score how the peripheral neuropathy interferes with daily functions of living. A small sample of blood will be taken at the completion of the paclitaxel or nab-paclitaxel infusion to measure levels of paclitaxel. The participant will then be sent home with capsules of NIAGEN® to take twice daily. Each week upon return to the clinic a small sample of blood will be taken before the infusion of paclitaxel to measure biomarkers for NIAGEN®, and other samples of blood will be taken to evaluate clinical chemistries, kidney, and liver function. Another sample of blood will be obtained after the paclitaxel or nab-paclitaxel infusion to measure levels of paclitaxel or nab-paclitaxel. The health care provider will meet with the patient each week to score the overall severity of the peripheral neuropathy, and the participant will answer another questionnaire with more specific questions. Once a month, the participant will be asked to fill out a second questionnaire. Participants will take 300 mg/day NIAGEN® in the first week and 1000 mg/day in the subsequent 11 weeks. The study will conclude one week after the 12th infusion of paclitaxel or nab-paclitaxel. Health care providers will contact the participant at various times up to 6 months to monitor their status.

Beginning with completion of the trial by the 10th participant and continuing with each subsequent participant up to 39, we will use a Bayesian statistical approach (Lee and Liu, 2008; i.e. predictive probability) to determine whether NIAGEN® has prevented a worsening of the peripheral neuropathy. This approach we let us make an early determination of futility. We will also determine whether NIAGEN® has decreased the need to delay or diminish the doses of paclitaxel or nab-paclitaxel due to severity of the peripheral neuropathy. The results of this trial will inform the design of a subsequent randomized, placebo-controlled, blinded clinical trial.

All subjects with stage IV breast cancer, platinum-resistant recurrent ovarian, peritoneal, endometrial, or fallopian tube cancer, or platinum-resistant recurrent or metastatic head and neck cancer will receive 300 mg NIAGEN®) daily for one week followed by dose escalation to 1000 mg daily for 11 weeks upon reporting the development of grade 1 sensory neuropathy. Those presenting with a residual sensory neuropathy of ≤ 2 as a result of prior chemotherapy will also be enrolled.

NR in Chemo-induced Peripheral Neuropathy

Nicotinamide Riboside (NR) in Paclitaxel-induced Peripheral Neuropathy

All of the individual participant data collected during the trial, after de-identification, will be shared with researchers who provide a methodologically sound proposal to achieve aims in the approved proposal. The IPD will be available to sharing immediately after publication and ending 5 years after article publication

Exploratory analysis of ability of the clinical version of the Total Neuropathy Score questionnaire to detect changes in CIPN severity over time. Unlike the CTCAE or the FACT\&GOG-NTX questionnaires, the TNS is a patient reported outcome measure. HIghest score (worse neuropathy is 24, lowest score is 0. Outcome assessed difference between end of treatment and screening. A positive number indicates improvement in neuropathy

The primary outcome variable is defined as no worsening of the grade of peripheral sensory neuropathy as scored according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 guidelines. Per the CTCAE a score of 1 would be assigned in the instance of parethesias or a loss of deep tendon reflexes. A score of 2 would be assigned in the instance of moderate symptoms that limit instrumental activities of daily living. A score of 3 would be assigned in the instance of severe symptoms that limit self-care activities of daily living. Because the outcome measure is defined as no worsening of the grade, it was recorded as either "yes"( i.e. it worsened) or "no" (i.e. it did not worsen).

Quantitate the percentage of patients that experience a dose reduction of paclitaxel or nab-paclitaxel therapy due to neuropathy.

Count the number of (i.e. the incidence) of dose reduction events due to neuropathy (each occasion of dose reduction is a separate event);

Quantitate the total cumulative dose of paclitaxel administered over the 12 weeks.

Difference in Score on the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - neurotoxicity questionnaire at the end of treatment; i.e. Score at screening - score at end of treatment. This questionnaire asks 11 questions that are specific to chemotherapy-induced peripheral neuropathies. Maximum score is 44, minimum score is 0. Positive differences indicate a decrease in neuropathy. Negative differences indicate a worsening of neuropathy. Zero means unchanged.

National Cancer Institute (NCI)

ChromaDex, Inc.

Donna Hammond, PhD

Professor

Subjects were queried for adverse events by phone interview 1, 3 and 6 months after end of treatment.

Daily oral administration of nicotinamide riboside 300 mg (150 mg a.m. and p.m.) for one week with dose escalation to 1000 mg (500 mg a.m. and p.m.) for remaining 11 weeks.

Nicotinamide Riboside: Capsule

NIAGEN®)

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Plasma sample obtained before NIAGEN treatment begun

NAD concentration plasma levels

Plasma samples obtained before NIAGEN treatment begun

1-methyl-nicotinamide plasma levels

Plasma sample obtained 10-20 min after taxane infusion ended

one sample not submitted due to subject testing COVID positive and withdrawing from study

paclitaxel plasma levels

This trial was limited to a non-curative population of women receiving taxane chemotherapy without added platinum-based agents. Difficulty in recruiting this small population led to eventual termination of the trial. Dose escalation to 1000 mg/day did not occur for any subject due to physician concerns that subjects were not tolerating the 300 mg dose well.

Donna L. Hammond, Ph.D Professor

Data are reported for the 4 subjects who took at least one dose of NIAGEN. End of treatment was originally defined as within 2 weeks after 12 weeks of NIAGEN treatment ended (i.e. a study duration of \~14 weeks). If a patient withdrew before completing 12 weeks of treatment, the end of treatment was designated as one week after withdrawal from the study. The longest that any participant was on NIAGEN was three weeks. Therefore, the time frame of the study has been adjusted to \~4 weeks.

Number of Participants With No Worsening in the Grade of Peripheral Sensory Neuropathy as Scored by CTCAE

Data are reported for the only subject who received more than 1 dose of taxane chemotherapy before withdrawal from the trial. That subject patient received only 2 doses of taxane over a period of 3 weeks. No patient completed the full 12 weeks of the trial. Therefore, the time frame of the study has been adjusted from the originally envisioned 12 weeks to \~3 weeks.

Percentage of Patients in Which Dose of Paclitaxel or Nab-Paclitaxel is Reduced Due to CIPN

Data are reported for the only subject who received more than 1 dose of taxane chemotherapy before withdrawal from the trial. That patient received only 2 doses of taxane over a period of 3 weeks. The original aim was to assess dose reduction over the 12 weeks of paclitaxel treatment, but no patient completed the 12 weeks of treatment. As the longest that any patient was on NIAGEN was 3 weeks, the time frame has been adjusted accordingly.

Number of Dose Reduction Events

Data are reported for the 1 subject who received taxane infusions after starting NIAGEN treatment. They received 2 infusions over a period of three weeks of NIAGEN treatment.

Total Dose of Paclitaxel Administered

Data are reported for the three subjects who took at least one dose of NIAGEN and completed the FACT questionnaire. End of treatment was originally defined as within 2 weeks after 12 weeks of NIAGEN treatment ended (i.e. a study duration of \~ 14 weeks). If a patient withdrew before then, the end of treatment was designated as one week after withdrawal. Unfortunately, the longest that any patient was on NIAGEN was three weeks. Therefore, the time frame has been adjusted to \~4 weeks.

Difference in Score Between Baseline and End of Treatment for the FACT&GOG-NTX Subscale .

Data are reported for the three subjects who took at least one dose of NIAGEN and completed the TNS evaluation. No patient completed the full 12 weeks of the trial. Therefore, the measure was made at end of treatment, which was designated as one week after they ceased NIAGEN treatment. The longest any one patient was on NIAGEN was three weeks. Hence the time frame was adjusted to 4 weeks.

Difference in Total Neuropathy Score Between Screening and End of Treatment

Paclitaxel levels in plasma were measured \~30 min after each infusion of taxane. This was undertaken to ascertain whether NIAGEN altered plasma levels of paclitaxel because increases or decreases in plasma levels of paclitaxel by itself could lead to an apparent worsening or improvement, respectively, in CIPN and confound interpretation of NIAGEN's effect.

Data are reported for three subjects in which paclitaxel levels were obtained before NIAGEN and after NIAGEN treatment, which ranged from one to three weeks. The plasma concentration for the last blood sample obtained after NIAGEN treatment

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
PROMOTE Study: Prediction of Response Of HorMOnal Treatment in Advanced and Recurrent Endometrial Cancer	NCT03621904	Endometrial Can... Endometrial Can... Endometrial Can...	Hormonal Antine...	18 Years - 110 Years	Radboud University Medical Center
PROMOTE Study: Prediction of Response Of HorMOnal Treatment in Advanced and Recurrent Endometrial Cancer	NCT03621904	Endometrial Can... Endometrial Can... Endometrial Can...	Hormonal Antine...	18 Years - 110 Years	Radboud University Medical Center
Self-Advocacy Serious Game in Advanced Cancer	NCT03339765	Ovarian Cancer ... Ovarian Cancer ... Breast Cancer S... Cervical Cancer... Cervical Cancer... Cervical Cancer... Endometrial Can... Endometrial Can... Vulvar Cancer, ... Vulvar Cancer, ... Vaginal Cancer ... Vaginal Cancer ... Vaginal Cancer ...	Strong Together...	18 Years -	University of Pittsburgh
PROMOTE Study: Prediction of Response Of HorMOnal Treatment in Advanced and Recurrent Endometrial Cancer	NCT03621904	Endometrial Can... Endometrial Can... Endometrial Can...	Hormonal Antine...	18 Years - 110 Years	Radboud University Medical Center
NR in Chemo-induced Peripheral Neuropathy	NCT03642990	Chemotherapy-in... Breast Cancer M... Platinum-resist... Head and Neck C... Endometrial Can...	Nicotinamide Ri...	18 Years - 85 Years	University of Iowa
NR in Chemo-induced Peripheral Neuropathy	NCT03642990	Chemotherapy-in... Breast Cancer M... Platinum-resist... Head and Neck C... Endometrial Can...	Nicotinamide Ri...	18 Years - 85 Years	University of Iowa

Spots Global Cancer Trial Database for endometrial cancer stage iv