A Phase II Randomized Trial of Immunotherapy Plus Radiotherapy in Metastatic Genitourinary Cancers

NCT ID: NCT03115801

Last Updated: 2021-09-22

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-30
• Study Completion Date: 2020-10-13

Brief Summary

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.

Detailed Description

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.

Conditions

Metastatic Renal Cell Carcinoma; Metastatic Urothelial Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Atezolizumab

Intervention Type: DRUG

Atezolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64.

Nivolumab

Intervention Type: DRUG

Nivolumab will be given to patients with renal cell carcinoma on days 1,15, 29, 43 and 57.

Pembrolizumab

Intervention Type: DRUG

Pembrolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64.

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.

Group Type: ACTIVE_COMPARATOR

Atezolizumab

Intervention Type: DRUG

Atezolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64.

Nivolumab

Intervention Type: DRUG

Nivolumab will be given to patients with renal cell carcinoma on days 1,15, 29, 43 and 57.

Radiation & immunotherapy

Intervention Type: 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.

Interventions

Atezolizumab

Atezolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64.

Intervention Type: DRUG

Nivolumab

Nivolumab will be given to patients with renal cell carcinoma on days 1,15, 29, 43 and 57.

Intervention Type: DRUG

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.

Intervention Type: RADIATION

Pembrolizumab

Pembrolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64.

Intervention Type: DRUG

Other Intervention Names

Immunotherapy; Tecentriq; Keytruda

Eligibility Criteria

Inclusion Criteria

1. Ability to understand and the willingness to sign a written informed consent document;

2. Any prior therapy is permitted except prior therapy with PD1/PDL1 inhibitor.

3. Histologic diagnosis of metastatic renal cell carcinoma or urothelial cancer;

4. Patients must have at least 2 distinct measurable metastatic sites at least 1 cm or larger in their largest diameter per RECIST 1.1

5. Patients must have adequate organ and marrow function as defined by initial laboratory tests.

6. At least 2 weeks since last chemotherapy and 4 weeks since last immunotherapy treatment.

7. Performance status Eastern cooperative oncology group (ECOG) 0-1

8. Men and women, ages > 18 years of age.

9. Life expectancy > 3 months

10. Stable brain metastases for at least 4 weeks and not steroid dependent

11. Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the study in such a manner that the risk of pregnancy is minimized. Should a woman become pregnant or suspect she is pregnant while she is enrolled in this study, she should inform her treating physician immediately.

Exclusion Criteria

1. Patients having no lesions outside the field of radiation thus nullifying the ability to measure an abscopal effect;

2. 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;

3. 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];

4. 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;

5. 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).

6. A history of prior treatment with PD-1/PDL-1blocking antibody;

7. Patients who have had immunotherapy within 4 weeks prior to entering the study.

8. 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;

9. Patients undergoing therapy with other investigational agents or other chemotherapy agents;

10. Women who:

1. are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 8 weeks after cessation of study drug, or

2. have a positive pregnancy test at baseline, or

3. are pregnant or breastfeeding

11. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Weill Medical College of Cornell University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Himanshu Nagar, M.D.

Role: PRINCIPAL_INVESTIGATOR

Weill Cornell Medicine - New York Presbyterian Hospital

Locations

Weill Cornell Medicine - New York Presbyterian Hospital

New York, New York, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

1606017369

Identifier Type: -

Identifier Source: org_study_id