Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Symptoms and General Pathology

Carcinoma, Non-Small-Cell Lung

Neoplasm Metastasis

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

All Drugs and Chemicals

Immunomodulating Agents

Chemotherapy Chemoradiotherapy Radiotherapy Immunotherapy Or a combination of above

SABR combined immunotherapy

Radiotherapy combined immunotherapy

Decision tool

Iva Halilaj, Msc

Relinde Lieverse, MD

Philippe Lambin, Prof. MD

This is a trial-specific (NCT03705403) decision aid (tPDA) for stage IV NSCLC patients that might want to participate.

We want to investigate if a tPDA would be (significantly) helpful for these patients in making a decision.

ImmunoSABR has a complex study design, we expect that the patients get a better overview of the trial via the tPDA because you can bring multiple tools together. (text, video, questions, pictures, timelines, etc.)

A lung cancer patient might want to take part in the ImmunoSABR phase 2 trial (NCT03705403). Before they can decide, it is important that the patients understand why the research is being done and what it would involve for them.

This tPDA will give information about this trial via text, small movies, quiz and preferences. In the end, the patient will receive an overview of their choices.

Detailed Description ImmunoSABR:

IMMUNOSABR will include 126 patients. In this single-stage controlled randomised open-label phase II trial, we aim to demonstrate an absolute increase in progression-free survival (primary endpoint). PFS will be determined as the time between randomisation and disease progression, according to RECIST 1.1, death due to any cause or last patient contact alive and progression-free. Patients will be randomized between control (no immunocytokine) and experimental arms (with immunocytokine L19-IL2) in a 1:1 ratio. The accrual period will be 29 months (or 2.41 years), and the minimum follow-up will be 18 months (or 1.5 years), making the total study duration 47 months. Comparison between control and experimental arms will be made using the Log-Rank statistic. This test for superiority will be one-sided with the desired type I error of 0.10 and power of 0.90.

Patients enrolled in the trial will be randomised into the control arm (C-arm) or experimental arm (E-arm).

C-arm: Standard of Care (SOC) according to the local and national guidelines: (wait and see or surgery and/or chemotherapy and/or standard (symptomatic) radiotherapy and/or SABR, oligometastatic disease.

E-arm: SABR (oligometastatic disease) or radiotherapy (diffuse disease) + L19-IL2 up to 6 cycles (+ aPD(L)1 if SOC) The expected 1.5-year PFS is 15% in the C-arm and 35% in the E-arm. A sample size of 116 patients (58 patients per treatment arm) is needed to show this difference of 20% in PFS, using a logrank test with a two-sided alpha of 0.05 and power of 85%. Patients will be evenly divided over the two arms. Assuming a drop-out rate of 10%, a total of 126 patients (63 per arm) need to be included.

Primary objective The main objective of the trial is to test if the activity of the combination of (SAB)R and L19-IL2 in patients with metastatic NSCLC will result in improved progression-free survival (PFS) compared to the SOC.

Secondary Objectives

Assessment of the PFS of the patient cohort, at 5 years after randomisation. Assessment of the overall survival of the patient cohort, at 5 years after randomisation.

To assess the toxicity of this treatment schedule; To assess Quality of Life (QoL); To assess the occurrence of an Out of Field Radio-Immune (OFRI) response / abscopal effect using imaging; To assess the occurrence of an In Field Radio-Immune (IFRI) response using imaging; To perform correlative biomarker studies related to treatment response.

Exploratory endpoints:

Correlative biomarker studies:

Tumour tissue: e.g EDB expression, non-synonymous mutations, immune monitoring; Blood: e.g. EDB expression, cfDNA, and immune monitoring; Radiomics on CT and if available MRI; Faeces: diversity in microbiota. iRECIST Tumour grow kinetics

Trial-specific Patient Decision Aid (tPDA) of the ImmunoSABR Phase 2

Patients' decisional needs (development phase):semi-structured interviews with patients about the decision about their treatment, and what information the patients need to make.

Quantitative research using a questionnaire based on the International Standard ISO-9242-11. This questionnaire measure to what extent the decision aid is easy to use. Answers will be clear for the patient; agree, neutral, disagree.

Decisional conflict will be assessed using the DCS (Decisional conflict scale): change in DCS between baseline group (usual care) and ImmunoSABR clinical trial. Answers will be clear for the patient; agree,neutral, disagree. Items are scored and summed. High total score will be in favour of the tPDA

Patient's preference to participate in medical decisions will be assessed using the 3-item Control Preference Scale (CPS):change in CPS between baseline group (usual care) and ImmunoSABR clinical trial . Questions and answers will be clear for the patient; agree, neutral, disagree. Items are scored and summed. High total score will be in favour of the tPDA

Patient's perception of the shared decision-making process will be assessed using the (shared decision making) SDM-Q9 instrument for patients: change in SDM between baseline group (usual care) and ImmunoSABR clinical trial. 9 questions with clear answers; totally disagree, strongly disagree, disagree, agree, strongly agree, totally agree.

Doctor's perception of the shared decision-making process will be assessed using the SDM-Q9 instrument for professionals: change in SDM between baseline group (usual care) and ImmunoSABR clinical trial. 9 questions with clear answers; totally disagree, strongly disagree, disagree, agree, strongly agree, totally agree.

Patients satisfaction with the tPDA will be tested via questions with predefined answers; agree,neutral, disagree. Items are scored and summed. High total score will be in favour of the tPDA

Patients recommendation regarding the tPDA will be tested via questions with predefined answers; agree, neutral, disagree. Items are scored and summed. High total score will be in favour of the tPDA

Maastricht University

Digestive System Diseases

Carcinoma

Carcinoma, Hepatocellular

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Antineoplastic Agents

Capecitabine

Antimetabolites

Capecitabine in HCC

Muhammad K Anis, MD

Zaigham Abbas, MD

Wasim Jafri, MD

In patients with unresectable/advanced Hepatocellular Carcinoma receiving Capecitabin, we anticipate that the proposed chemotherapy will have a delay in progression of the disease . It is also expected that proposed chemotherapy will have acceptable toxicity and Quality of life.

II. OBJECTIVES

II.A. Primary Objectives: To evaluate response rate (RR) and overall survival (OS).

II.B. Secondary Objective: To evaluate the time to progression (TTP), median time to response (MTR), toxicity and quality of life (QOL).

III. STUDY DESIGN:

III.A. Inclusion criteria:

1. Written informed consent. 2. Age between 18 and 70 years. 3. Documented by at least 2 out of three mentioned criteria and evidence of non-resectability.

1. Radiological either CT Scan/US abdomen
2. Biopsy,
3. Serum alphafeto protein level 4. Multi centric hepatoma or TNM Classification Stage IV. 5. Child's class B or C with a Child's score of maximum 11. 6. No other active malignancy except localized basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.

   7. Life expectancy of greater then 3 months. 8. Current laboratory values must be within the limits listed below: Haemoglobin \> 8 g/dL WBC \> 4,000/uL Absolute Neutrophil Count \> 1,500/uL Platelets \> 75,000/uL 9. ECOG Performance status of \< 2. 10. Patients who have received adjuvant or neoadjuvant therapy are eligible. A minimum interval of 4 weeks since last chemotherapy will be required.

   11. Prior radiotherapy will be allowed if it did not involve a site used to assess response and 4 weeks have elapsed since completion of radiotherapy.

   III.B. Exclusion criteria:

   1. History of allergic reaction to compound chemically related to CAP. 2. Concomitant or previous malignancies within five years other than basal or squamous cell carcinoma of the skin and carcinoma in situ of the cervix. 3. Active, uncontrolled infection. . 5. Concurrent medical problems which could limit the life expectancy or the ability of the patient to receive chemotherapy.

   6. Mental condition that could limit the patient in comprehending the concept of clinical trial or complying with its requirements.

   7. Brain or leptomeningeal involvement. 8. Pre-existing neurotoxicity of \>=grade 2. 9. Concomitant radiotherapy, unless localised for bone pain control or palliation.

   10. Being of reproductive potential and not agreeing to practice an effective contraceptive method.

   11. Pregnancy or lactation. 12. Severe renal impairment with Creatinine clearance \<30ml/minute. 13. Documented Cardiomyopathy or severe coronary artery disease, or history of arrhythmias.

   IV. PATIENT REGISTRATION

   All patients entering this study must be registered by contacting:

   Drs. Kashif Anis/Zaigham Abbas -Research Co-ordinators The Aga Khan University Hospital, Dept of Medicine/ Medical Oncology. Stadium Road, P.O. Box: 3500, Karachi, 74800, Pakistan Tel (021) 493-0051

   V. THERAPY

   This is a Phase II trial studying chemotherapy with CAP in non-resectable HCC. Prior chemotherapy, radiation therapy, surgery is permitted. Staging is required with a CAT scan/Ultrasound of abdomen and bone scan if necessary. Pre study evaluation should include CBC, renal functions assessment, and liver function tests. Patients will require independent evaluation with medical oncologist/gastroenterologist prior to being included in the study. Chemotherapy would be given in cycles of 21 days. CAP would be given as oral tablets twice daily starting from day 1 to day 14. Medication with standard anti-emetics, which may include serotonin antagonist, may be used before administration of chemotherapy. Duration of chemotherapy administration would be determined by the patient's response. A patient who has progressive disease, is not able to tolerate chemotherapy and has unacceptable toxicity would be taken off the study. Patients, who have a response, will continue on chemotherapy till progression of disease or inability to tolerate chemotherapy is documented.

   VI. DOSE MODIFICATION

   Hematologic Toxicity:

   Chemotherapy will be held if ANC \< 1,500/uL, and/or platelet count is \< 50,000/uL. Treatment will resume when counts recover. Growth factors can be used in subsequent cycles if delay is secondary to neutropenia. If there is no recovery after 3 weeks of delay, the patient will be taken off the study.

   Renal dysfunction:

   Creatinine Clearance mL/min Dose \>50 100% 30-50 75% \<30 0%(no treatment is given)

   Elevated Liver Function Tests:

   In the event that bilirubin is elevated during the study, the next cycle will be delayed by a maximum of 2 weeks. (The following dose modification in the dose of capecitabine will be made if the AST and/or ALT and/or alkaline phosphatase levels are elevated:

   AST/ALT Alkaline Phosphatase Recommended dose (%) \> 1.5- \< 2.5 x normal \< 2.5 x normal 75% \> 2.5- \< 5 x normal \> 2.5- \< 5 x normal 50% \> 5 x normal \> 5 x normal Dose delay by a maximum of 2 weeks. If no recovery is noted; the patient should go off study.

   Cardio toxicity:

   Significant drop in left ventricular ejection fraction and/or clinical signs and symptoms of cardiac failure will result in discontinuation from the study.

   Dose Modification:

   Dose reduction is planned if significant (Grade III/IV) hematologic or non-hematologic toxicities are observed. CAP shall be reduced by 25% with grade III/IV toxicity occur. Patient should be taken off study if a life threatening complication occurs. All grade III/IV toxicities should be recorded in detail including the dates of onset and resolution/outcome. GI toxicity of grade II including severe diarrhea, nausea, vomiting and stomatitis, dose modification will be done as, it will be held for 1 week along with symptomatic treatment , if no improvement for 2 weeks then patient will be taken off the study.

   VII. SERIOUS ADVERSE EVENT REPORTING

   All serious events (as defined in Appendix E of protocol) must be reported, as soon as you are aware of them to:

   Drs. Kashif Anis/Zaigham Abbas , at the Aga Khan University Hospital VIII. EVALUATION

   Evaluation before Treatment:

   Patient should have evaluation by gastroenterology/oncology to determine eligibility.

   All Patients should have:

   Diagnosis of hepatoma with the help of Biopsy if possible, or by the help of CT Scan or Serum alpha fetoprotein level, fulfilling 2 out of 3 criteria.

   Complete history and physical examination. CBC, differential, platelet count, serum sodium, potassium, glucose, calcium, creatinine, bilirubin, alkaline phosphatase, AST, ALT ,alpha fetoprotein(AFP), prothrombin time PT and Serum Albumin.

   CT scan of the abdomen with contrast. Cardiac evaluation of LVEF CT scans and plain x-rays if clinically indicated.

   Evaluation during Chemotherapy:

   CBC, differential, platelets count, sodium, potassium, creatinine, glucose, bilirubin, alkaline phosphatase, AST/ALT.

   CBC should be repeated prior to every chemotherapy course.

   Re-evaluation of response after every 3 courses of chemotherapy would be done radio logically by repeating a CT scan/x rays as indicated by sites of disease involvement.

   Evaluation After chemotherapy:

   All patients will be followed thereafter cessation of chemotherapy due to progression of disease, every three to six months until a total of five years for evaluation of five-year disease free and overall survival.

   Evaluation of toxicity profile.

   This should be based either on the NCIC common toxicity criteria (attached at the end), or any other major toxicity criteria (e.g. NCI), and documented in the attached form.

Phase II Trial of Capecitabine for the Treatment of Unresectable/ Metastatic or Advanced Hepatocellular Carcinoma(HCC)

Aga Khan University

Muhammad Kashif Anis

Skin and Connective Tissue Diseases

Recurrence

Breast Neoplasms

Breast Diseases

Skin Diseases

Disease Attributes

Paclitaxel

Albumin-Bound Paclitaxel

Bevacizumab

Trebananib

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Paclitaxel 90 mg/m² IV QW (3 on/1 off) + bevacizumab 10 mg/kg IV Q2W + AMG 386 10 mg/kg IV QW

Paclitaxel 90 mg/m² IV QW (3 on/1 off) + Open Label AMG 386 10 mg/kg IV QW

Paclitaxel 90 mg/m² IV QW (3 on/1 off) + bevacizumab 10 mg/kg IV Q2W + AMG 386 3 mg/kg IV QW

Paclitaxel 90 mg/m² IV QW (3 on/1 off) + bevacizumab 10 mg/kg IV Q2W + AMG 386 placebo IV QW

AMG 386 Placebo

AMG 386

This is a phase 2, randomized, placebo controlled, multi-center study to estimate the treatment effect and evaluate the safety and tolerability of AMG 386 in combination with paclitaxel and paclitaxel/bevacizumab in the treatment of subjects with Her2-negative metastatic or locally recurrent breast cancer.

AMG 386 is a man-made medication that is designed to stop the development of blood vessels in cancer tissues. Cancer tissues rely on the development of new blood vessels, a process called angiogenesis, to obtain a supply of oxygen and nutrients to grow.

Primary Objective: To estimate the treatment effect as measured by progression free survival (PFS) of subjects receiving AMG 386 (at 2 doses) in combination with paclitaxel + bevacizumab relative to paclitaxel + bevacizumab + placebo.

Secondary Objective(s):

* To compare the treatment effect as measured by PFS of subjects receiving open-label AMG 386 in combination with paclitaxel relative to paclitaxel + bevacizumab + placebo
* To compare the treatment effect as measured by PFS of subjects receiving AMG 386 in combination with paclitaxel and bevacizumab relative to paclitaxel + AMG 386
* To evaluate the safety and tolerability of the combination and non-bevacizumab regimens
* To estimate other measures (RR, DOR, TTR, TTP) of treatment effect
* To evaluate the pharmacokinetics (PK) of AMG 386 and bevacizumab when used in combination
* To estimate the incidence of anti-AMG386 antibody formation

Exploratory Objective(s):

* To explore the pharmacodynamic (PD) response as assessed by changes in blood levels of angiogenic cytokines, tumor apoptosis, and other markers
* To explore the association of histological features and selected immunologic, biochemical, pharmacogenetic, or angiogenic markers in tumor biopsies, plasma, or serum samples with safety and/or efficacy outcomes

Study Design:

This is a phase 2, randomized, placebo controlled, multi-center study to estimate the treatment effect and evaluate the safety and tolerability of AMG 386 in combination with paclitaxel and paclitaxel/bevacizumab in the treatment of subjects with Her2-negative metastatic or locally recurrent breast cancer.

Two hundred twenty subjects will be randomized 1:1:1:1 to each of the following arms:

Arm A: Paclitaxel 90 mg/m² IV QW (3 on/1 off) + bevacizumab 10 mg/kg IV Q2W + AMG 386 10 mg/kg IV QW Arm B: Paclitaxel 90 mg/m² IV QW (3 on/1 off) + bevacizumab 10 mg/kg IV Q2W + AMG 386 3 mg/kg IV QW Arm C: Paclitaxel 90 mg/m² IV QW (3 on/1 off) + bevacizumab 10 mg/kg IV Q2W + AMG 386 placebo IV QW Arm D: Paclitaxel 90 mg/m² IV QW (3 on/1 off) + Open Label AMG 386 10 mg/kg IV QW To maintain the double-blind in arms A, B, and C, each subject will be infused weekly with a volume of investigational product equivalent to 10 mg/kg AMG 386 IV. Arm D will receive open label AMG 386 and will not receive a placebo for bevacizumab.

Subjects will be discontinued from study treatment at any time for radiographic disease progression, clinical progression, unacceptable toxicity, subject withdrawal of consent, or death.

Subjects alive at the time of discontinuation of all study medications will be followed for up to 48 months from the date of the last subject enrolled into the trial to evaluate overall survival.

Radiological imaging to assess disease status will be performed every 8 weeks ± 7 days (2 cycles) for 2 years and then every 4 months ± 1 month thereafter during the study until subjects develop radiographic disease progression per the modified RECIST criteria. In addition, any subject who discontinues study drug treatment prior to disease progression will continue to have radiological imaging performed every 8 weeks ± 7 days during the long term follow up period if the subject has not been in the study for 2 years until the subject develops radiographic disease progression or begins a new treatment. If the subject has been on study for 2 years, radiological imaging every 4 months ± 1 month will be performed during long term follow-up period until the subject develops radiographic disease progression or begins a new treatment.

The overall study design is described by a study schema immediately following this synopsis. Amgen Global Safety (AGS) will charter a data review team (DRT) that is independent of the team conducting the study and will review unblinded safety data after 20, 40, and 80 subjects have been randomized and have had the opportunity to receive at least 1 cycle (4 weeks) of study treatment.

Phase 2 Study of AMG 386 Plus Paclitaxel With or Without Bevacizumab as First Line Therapy in Her2-Negative Breast Cancer Patients

A Randomized, 4-Arm, Placebo-Controlled Phase 2 Trial of AMG 386 in Combination With Bevacizumab and Paclitaxel or AMG 386 Plus Paclitaxel as First-Line Therapy in Subjects With Her2-Negative, Metastatic or Locally Recurrent Breast Cancer

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Trial-specific Patient Decision Aid (tPDA) of the ImmunoSABR Phase 2	NCT04604470	NSCLC Stage IV Lung Cancer Non Small Cell ... Metastatic Canc...	Decision tool	18 Years -	Maastricht University
Phase II Trial of Capecitabine for the Treatment of Unresectable/ Metastatic or Advanced Hepatocellular Carcinoma(HCC)	NCT00464295	Carcinoma, Hepa...	Capecitabine in...	18 Years -	Aga Khan University
Phase II Trial of Capecitabine for the Treatment of Unresectable/ Metastatic or Advanced Hepatocellular Carcinoma(HCC)	NCT00464295	Carcinoma, Hepa...	Capecitabine in...	18 Years -	Aga Khan University
Trial-specific Patient Decision Aid (tPDA) of the ImmunoSABR Phase 2	NCT04604470	NSCLC Stage IV Lung Cancer Non Small Cell ... Metastatic Canc...	Decision tool	18 Years -	Maastricht University
Phase 2 Study of AMG 386 Plus Paclitaxel With or Without Bevacizumab as First Line Therapy in Her2-Negative Breast Cancer Patients	NCT00511459	Locally Recurre...	AMG 386 Placebo AMG 386 Bevacizumab AMG 386 AMG 386 Paclitaxel	18 Years -	Amgen

Spots Global Cancer Trial Database for phase 2 trial