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Lack of accrual
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The trial is open to patients who have metastatic renal cell carcinoma/urothelial (bladder) carcinoma with at least 2 measurable sites of disease. All eligible patients will be randomly assigned to immunotherapy(nivolumab/atezolizumab/pembrolizumab) versus immunotherapy (nivolumab/atezolizumab/pembrolizumab) plus radiotherapy, 10 Gy x3 (conformally or by intensity modulation radiation therapy/Image-guided radiation therapy (IMRT/IGRT) to maximally spare normal tissue), to one of their measurable lesions.
The trial is open to patients who have metastatic renal cell carcinoma/urothelial (bladder) carcinoma with at least 2 measurable sites of disease. All eligible patients will be randomly assigned to immunotherapy(nivolumab/atezolizumab/pembrolizumab) versus immunotherapy (nivolumab/atezolizumab/pembrolizumab) plus radiotherapy, 10 Gy x3 (conformally or by IMRT/IGRT to maximally spare normal tissue), to one of their measurable lesions. For patients assigned to the immunotherapy plus radiotherapy arm, immunotherapy treatment starts with the first radiotherapy fraction. Nivolumab will be given every 2 weeks for patients with metastatic renal cell cancer and atezolizumab/pembrolizumab will be given every 3 weeks for patients with metastatic urothelial cancer. Patients will be re-imaged at 9 week (year 1) or 12 week (years 2-3) intervals and evaluated for response (defined as an objective response of measurable metastatic sites outside the radiation field). This response will be evaluated with CT scans in non-irradiated measurable metastatic sites per RECIST version 1.1. Patients will continue to receive their respective immunotherapies for up to three years or until disease progression or until a dose limiting toxicity is reached.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A - immunotherapy alone | Active Comparator | Patients with Renal Cell carcinoma will receive Nivolumab alone Days 1, 15, 29, 43 and 57. Patients with Urothelial cancer will receive Atezolizumab or Pembrolizumab on Days 1, 22, 43 and 64. |
|
| Arm B - Radiation & immunotherapy | Active Comparator | Radiation is given to one lesion, 30 Gy in 3 fractions of 10 Gy, every other day. On the day of radiation (Day 1) immunotherapy is administered and repeated on the scheduled days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nivolumab | Drug | Nivolumab will be given to patients with renal cell carcinoma on days 1,15, 29, 43 and 57. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Best Overall Response Rates of Immunotherapy Alone and of Immunotherapy Plus Radiotherapy (to a Single Metastatic Site). | from 96 weeks | |
| Assess the Difference in Participants for the Best Overall Response Between the Two Groups, Immunotherapy Alone and of Immunotherapy Plus Radiotherapy(to a Single Metastatic Site). | from 96 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Progression Free Survival | from 96 weeks | |
| Number of Participants Who Experienced Toxicities Related to Immunotherapy and Immunotherapy Plus Radiotherapy Treatment Groups | from 96 weeks |
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Inclusion Criteria:
Exclusion Criteria:
Patients having no lesions outside the field of radiation thus nullifying the ability to measure an abscopal effect;
Any other malignancy from which the patient has been disease-free for less than 5 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix;
Autoimmune/auto inflammatory disease: Patients with a history of inflammatory bowel disease are excluded from this study as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], Systemic Lupus Erythematosus, autoimmune vasculitis [e.g., Wegener's Granulomatosis];
Any underlying medical or psychiatric condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events (AEs), such as a condition associated with frequent diarrhea;
Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to one month prior to or after any dose of PD-1/PDL-1 blocking antibody).
A history of prior treatment with PD-1/PDL-1blocking antibody;
Patients who have had immunotherapy within 4 weeks prior to entering the study.
Concomitant therapy with any of the following: interleukin -2 (IL-2), interferon or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigation therapies; or chronic use of systemic corticosteroids;
Patients undergoing therapy with other investigational agents or other chemotherapy agents;
Women who:
Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness
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| Name | Affiliation | Role |
|---|---|---|
| Himanshu Nagar, M.D. | Weill Cornell Medicine - New York Presbyterian Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Weill Cornell Medicine - New York Presbyterian Hospital | New York | New York | 10065 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm A - Immunotherapy Alone | Patients with Renal Cell carcinoma will receive Nivolumab alone Days 1, 15, 29, 43 and 57. Patients with Urothelial cancer will receive Atezolizumab or Pembrolizumab on Days 1, 22, 43 and 64. Nivolumab: Nivolumab will be given to patients with renal cell carcinoma on days 1,15, 29, 43 and 57. Atezolizumab: Atezolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64. Pembrolizumab: Pembrolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 20, 2020 |
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| Atezolizumab | Drug | Atezolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64. |
|
|
| Radiation & immunotherapy | Radiation | Radiation is given to one lesion, 30 Gray (Gy) in 3 fractions of 10 Gy each. over a one week interval (with a minimum of 36hrs between each fraction). On the day of radiation (Day 1) immunotherapy is administered and repeated on the scheduled days. Patients will receive radiation on Day 1 and immunotherapy will be given ± 24hr from Day 1. |
|
| Pembrolizumab | Drug | Pembrolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64. |
|
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| Participants Will be Measured for Overall Survival | from 96 weeks |
| FG001 | Arm B - Radiation & Immunotherapy | Radiation is given to one lesion, 30 Gy in 3 fractions of 10 Gy, every other day. On the day of radiation (Day 1) immunotherapy is administered and repeated on the scheduled days. Nivolumab: Nivolumab will be given to patients with renal cell carcinoma on days 1,15, 29, 43 and 57. Atezolizumab: Atezolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64. Radiation & immunotherapy: Radiation is given to one lesion, 30 Gray (Gy) in 3 fractions of 10 Gy each. over a one week interval (with a minimum of 36hrs between each fraction). On the day of radiation (Day 1) immunotherapy is administered and repeated on the scheduled days. Patients will receive radiation on Day 1 and immunotherapy will be given ± 24hr from Day 1. |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm A - Immunotherapy Alone | Patients with Renal Cell carcinoma will receive Nivolumab alone Days 1, 15, 29, 43 and 57. Patients with Urothelial cancer will receive Atezolizumab or Pembrolizumab on Days 1, 22, 43 and 64. Nivolumab: Nivolumab will be given to patients with renal cell carcinoma on days 1,15, 29, 43 and 57. Atezolizumab: Atezolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64. Pembrolizumab: Pembrolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64. |
| BG001 | Arm B - Radiation & Immunotherapy | Radiation is given to one lesion, 30 Gy in 3 fractions of 10 Gy, every other day. On the day of radiation (Day 1) immunotherapy is administered and repeated on the scheduled days. Nivolumab: Nivolumab will be given to patients with renal cell carcinoma on days 1,15, 29, 43 and 57. Atezolizumab: Atezolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64. Radiation & immunotherapy: Radiation is given to one lesion, 30 Gray (Gy) in 3 fractions of 10 Gy each. over a one week interval (with a minimum of 36hrs between each fraction). On the day of radiation (Day 1) immunotherapy is administered and repeated on the scheduled days. Patients will receive radiation on Day 1 and immunotherapy will be given ± 24hr from Day 1. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Full Range | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Best Overall Response Rates of Immunotherapy Alone and of Immunotherapy Plus Radiotherapy (to a Single Metastatic Site). | Posted | Count of Participants | Participants | from 96 weeks |
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| |||||||||||||||||||||||||||||||
| Primary | Assess the Difference in Participants for the Best Overall Response Between the Two Groups, Immunotherapy Alone and of Immunotherapy Plus Radiotherapy(to a Single Metastatic Site). | 3 participants on ARM A and 2 participants on ARM B could not be analyzed because they were withdrawn from the trial for disease progression. | Posted | Count of Participants | Participants | from 96 weeks |
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| Secondary | Number of Participants With Progression Free Survival | Posted | Count of Participants | Participants | from 96 weeks |
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| Secondary | Number of Participants Who Experienced Toxicities Related to Immunotherapy and Immunotherapy Plus Radiotherapy Treatment Groups | Posted | Count of Participants | Participants | from 96 weeks |
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| Secondary | Participants Will be Measured for Overall Survival | Posted | Count of Participants | Participants | from 96 weeks |
|
2 years
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm A - Immunotherapy Alone | Patients with Renal Cell carcinoma will receive Nivolumab alone Days 1, 15, 29, 43 and 57. Patients with Urothelial cancer will receive Atezolizumab or Pembrolizumab on Days 1, 22, 43 and 64. Nivolumab: Nivolumab will be given to patients with renal cell carcinoma on days 1,15, 29, 43 and 57. Atezolizumab: Atezolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64. Pembrolizumab: Pembrolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64. | 0 | 4 | 1 | 4 | 1 | 4 |
| EG001 | Arm B - Radiation & Immunotherapy | Radiation is given to one lesion, 30 Gy in 3 fractions of 10 Gy, every other day. On the day of radiation (Day 1) immunotherapy is administered and repeated on the scheduled days. Nivolumab: Nivolumab will be given to patients with renal cell carcinoma on days 1,15, 29, 43 and 57. Atezolizumab: Atezolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64. Radiation & immunotherapy: Radiation is given to one lesion, 30 Gray (Gy) in 3 fractions of 10 Gy each. over a one week interval (with a minimum of 36hrs between each fraction). On the day of radiation (Day 1) immunotherapy is administered and repeated on the scheduled days. Patients will receive radiation on Day 1 and immunotherapy will be given ± 24hr from Day 1. | 0 | 2 | 1 | 2 | 1 | 2 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal Pain | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment | Left lower Quadrant Abdominal Pain with urination |
|
| Dyspnea on Exertion | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment | Bilateral 2+ pitting edema (Grade 2) and shortness of breath (Grade 2) were observed. |
|
| Hip Fracture | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment | Right hip fracture |
|
| Hyperglycemia | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment | Hyperglycemia |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Back Pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Elevated Alkaline Phosphate | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Intermittent discomfort in the right buttock | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
The clinical trial did not reach the target number of subjects needed to achieve target power and was insufficient to produce statistically reliable results.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Sharanya Chandrasekhar | Weill Cornell Medicine | 6469623110 | shc2043@med.cornell.edu |
| Aug 17, 2021 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D002292 | Carcinoma, Renal Cell |
| D002295 | Carcinoma, Transitional Cell |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D007680 | Kidney Neoplasms |
| D014571 | Urologic Neoplasms |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052801 | Male Urogenital Diseases |
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| ID | Term |
|---|---|
| D000077594 | Nivolumab |
| D007167 | Immunotherapy |
| C000594389 | atezolizumab |
| D011827 | Radiation |
| C582435 | pembrolizumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D056747 | Immunomodulation |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D055585 | Physical Phenomena |
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| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
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| Units | Counts |
|---|---|
| Participants |
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| Units | Counts |
|---|---|
| Participants |
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