Nivolumab vs Nivolumab + Bevacizumab vs Nivolumab + Ipilimumab in Metastatic Renal Cell Carcinoma (mRCC)
Conditions
Kidney Cancer
Conditions: official terms
Carcinoma, Renal Cell - Kidney Neoplasms
Conditions: Keywords
Kidney Cancer, Metastatic Renal Cell Carcinoma, mRCC, Cytoreductive Nephrectomy, Presurgical therapy, Nivolumab, BMS-936558, Bevacizumab, Avastin, Anti-VEGF monoclonal antibody, fhuMab-VEGF, Ipilimumab, Yervoy, BMS-734016, MDX010
Study Type
Interventional
Study Phase
Phase 2
Study Design
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: Nivolumab Type: Drug
Name: Bevacizumab Type: Drug
Name: Ipilimumab Type: Drug
Overall Status
Recruiting
Summary
The goal of this clinical research study is to learn if nivolumab alone or nivolumab in combination with either bevacizumab or ipilimumab can help control metastatic kidney cancer. The safety of these drug combinations will also be studied.
Detailed Description
Study Groups:

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the roll of dice) to 1 of 3 study groups. This is done because no one knows if one study group is better, the same, or worse than the other group. You will have an equal chance of being assigned to each group.

If you are in Group N, you will receive nivolumab alone.

If you are in Group N-B, you will receive nivolumab and bevacizumab.

If you are in Group N-I, you will receive nivolumab and ipilimumab.

Study Drug Administration:

If you are in Group N, you will receive nivolumab by vein over about 60 minutes on Day 1 of Weeks 1, 3, and 5. You will not receive this drug again until Week 14. Starting at Week 14, you may begin receiving the drug again every 2 weeks.

If you are in Group N-B, you will receive nivolumab by vein over about 60 minutes and bevacizumab by vein over about 90 minutes on Day 1 of Weeks 1, 3, and 5. You will not receive these drugs again until Week 14. Starting at Week 14, you may begin receiving nivolumab again every 2 weeks.

If you are in Group N-I, you will receive nivolumab by vein over about 60 minutes and ipilimumab by vein over about 90 minutes on Day 1 of Weeks 1 and 4. You will not receive these drugs again until Week 14. Starting at Week 14, you may begin receiving nivolumab again every 2 weeks.

Study Visits:

If you are in Group N or Group N-B, on Day 1 of Weeks 1, 3, and 5 or if you are in Group N-I, during Day 1 of Weeks 1 and 4:

- You will have a physical exam.

- Blood (about 3-4 tablespoons) and urine will be collected for routine tests. During Week 1 only, this blood or urine will also be used for a pregnancy test if you can become pregnant.

- Blood (about 3-4 tablespoons) will be drawn for immune system testing.

All patients will have the following tests and procedures below:

During Week 8:

- You will have a physical exam.

- Blood (about 3-4 tablespoons) and urine will be collected for routine tests.

- Blood (about 3-4 tablespoons) will be collected for immune system testing.

- You will have CT or MRI scans to check the status of the disease.

You will have surgery on Week 10. During surgery, tumor tissue will be collected for immune system testing. You will sign a separate consent explaining the surgery and its risks.

After Surgery (during Week 14, 15, or 16):

- You will have a physical exam.

- Blood (about 3-4 tablespoons) and urine will be collected for routine tests.

- Blood (about 3-4 tablespoons) will be collected for immune system testing.

- You will have CT or MRI scans to check the status of the disease.

Length of Study:

You may continue taking the study drug(s) for up to 2 years after surgery. You will no longer be able to take the study drug(s) if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Your participation on the study will be over after the follow-up visits.

Follow-up Visits:

Every 3 months for the first 2 years after surgery, then every 6 months for the third year, then every year unless the disease get worse or if intolerable side effects occur:

- You will have a physical exam.

- Blood (about 3-4 tablespoons) and urine will be collected for routine tests.

- Blood (about 3-4 tablespoons) will be collected for immune system testing.

- You will have CT or MRI scans to check the status of the disease.

This is an investigational study. Nivolumab is not FDA approved or commercially available. It is currently being used for research purposes only. Ipilimumab is FDA approved to treat metastatic melanoma. Bevacizumab is approved for certain types of kidney cancer and several other types of cancer, including breast, colon, and lung cancer. It is not FDA approved for the treatment of metastatic kidney cancer. The study doctor can explain how the study drug(s) are designed to work.

Up to 45 participants will take part in this study. All will be enrolled at MD Anderson.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: Inclusion Criteria:

1. Patients must give written informed consent prior to initiation of therapy, in keeping with the policies of the institution. Patients with a history of major psychiatric illness must be judged able to fully understand the investigational nature of the study and the risks associated with the therapy.

2. Patients with histologically or cytologically confirmed metastatic clear cell RCC who are eligible for cytoreductive nephrectomy. The determination of resectability will ultimately lie in the clinical judgment of the urologist and medical oncologist involved in the care of the patient.

3. Patients must have measurable disease is defined as a lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) and measures >= 20 mm with conventional techniques or >= 10 mm with spiral CT scan. This does not include primary tumors, which will be removed.

4. Patients can have had prior treatment for RCC including prior surgery, radiation therapy, immunotherapy with IL-2 or interferon (but not anti-PD1 or anti-CTLA-4), target therapy with RTK inhibitors/mTOR inhibitors, or chemotherapy.

5. ECOG performance status <= 1.

6. Patients must have adequate organ and marrow function within 14 days as defined below: Absolute neutrophil count >= 1,500/uL, Platelets >= 100,000/uL, Hgb > 9.0 g/dL (may be transfused or receive epoetin alfa [e.g., Epogen®] to maintain or exceed this level), Total bilirubin <= 1.5 mg/dl, Serum creatinine <= 1.5 times the upper limit of normal or estimated CrCl >40mL/min, AST (SGOT) and/or ALT (SGPT) <= 2.5 X institutional upper limit of normal for patients without evidence of liver metastases, AST (SGOT) and/or ALT (SGPT) <= 5 X institutional upper limit of normal for patients with documented liver metastases.

7. Men and women >= 18 years of age

8. Female patients of childbearing potential (i.e. premenopausal, no hysterectomy) must have a normal plasma beta human chorionic gonadotropin (Beta-HCG) within 24 hours of enrollment and again on the day of starting therapy in the study due to the possible teratogenic effect. Patients with an elevated Beta-HCG will undergo appropriate evaluation to rule out pregnancy (i.e. referral to Gyn service, pelvic ultrasound) and if pregnancy is ruled out and elevated Beta-HCG is determined to be of tumor origin, patients will be permitted to proceed on study

9. Patients of child fathering or childbearing potential must agree to practice a form of medically acceptable birth control while on study, i.e. condoms.

Exclusion Criteria:

1. Any other malignancy from which the patient has been disease-free for less than 2 years, except for non-melanoma skin cancer, in situ carcinoma of any site.

2. Patients who have organ allografts.

3. Patients who have had major surgical procedure, open biopsy, or significant traumatic injury within 6 weeks with poorly healed wound prior to Day 0, or anticipation of need for major surgical procedure during the course of the study (other than defined by protocol); or fine needle aspirations or core biopsies within 7 days prior to Day 0.

4. Autoimmune disease: Patients with a history of Inflammatory Bowel Disease (including Crohn's disease and ulcerative colitis) are excluded from this study as are patients with a history of autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], Systemic Lupus Erythematosus, autoimmune vasculitis [e.g., Wegener's Granulomatosis]).

5. Known HIV, Hepatitis B/C and chronic hepatitis.

6. Any underlying medical condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events, such as a condition associated with frequent diarrhea.

7. Patients who have had a history of acute diverticulitis, abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, GI obstruction, abdominal carcinomatosis which are known risks factors for bowel perforation, should be excluded from the study.

8. Patients who have a primary brain tumor (excluding meningiomas and other benign lesions), any brain metastases, leptomeningeal disease, seizure disorders not controlled with standard medical therapy, history of stroke within the past year.

9. History of serious systemic disease, including myocardial infarction or unstable angina within the last 12 months, history of hypertensive crisis or hypertensive encephalopathy, uncontrolled hypertension (blood pressure of >140/90 mmHg) at the time of enrollment, New York Heart Association (NYHA) Grade II or greater congestive heart failure, unstable symptomatic arrhythmia requiring medication (patients with chronic atrial arrhythmia, i.e., atrial fibrillation or paroxysmal supraventricular tachycardia are eligible), significant vascular disease or symptomatic peripheral vascular disease.

10. Patients who have history of other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications.

11. Patients who have proteinuria at baseline. Patients who are unexpectedly discovered to have >=2+ proteinuria at baseline routine urinalysis should undergo a 24-hour urine collection, which must be an adequate collection and must demonstrate <=1 g of protein/24 hr to allow participation in the study.

12. Patients who have uncontrolled hypertension.

13. Patients who are on high dose steroid (e.g. > 10mg prednisone daily or equivalent) or other more potent immune suppression medications(e.g. infliximab).

14. Patients who have had flu, hepatitis, or other vaccines within a month prior to initiation of study drugs.

15. Patients who have clinical history of coagulopathy, bleeding diathesis or thrombosis within the past year.

16. Patients who have serious, non-healing wound, ulcer, or bone fracture.

17. Pregnancy (positive pregnancy test) or lactation.

18. Patients must not have received prior anticancer therapy with bevacizumab, anti-CLTA-4, or anti-PD1 for renal cell carcinoma. Patients receiving any concomitant systemic therapy for renal cell cancer are excluded.

19. Patients must not be scheduled to receive another experimental drug while on this study.

20. Patients who are on warfarin or heparin will be excluded from bevacizumab therapy although aspirin will be permitted.

21. Patients must not require total parenteral nutrition with lipids.

22. Any patients who cannot be compliant with the appointments required in this protocol must not be enrolled in this study.
Location
University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Status: Recruiting
Start Date
November 2014
Sponsors
M.D. Anderson Cancer Center
Source
M.D. Anderson Cancer Center
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page