DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more



Nivolumab vs Nivolumab + Bevacizumab vs Nivolumab + Ipilimumab in Metastatic Renal Cell Carcinoma (mRCC)

Information source: M.D. Anderson Cancer Center
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Kidney Cancer

Intervention: Nivolumab (Drug); Bevacizumab (Drug); Ipilimumab (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: M.D. Anderson Cancer Center

Official(s) and/or principal investigator(s):
Padmanee Sharma, MD, PHD, Principal Investigator, Affiliation: M.D. Anderson Cancer Center

Overall contact:
Padmanee Sharma, MD, PHD, Phone: 713-792-2830

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.

Clinical Details

Official title: A Pilot Randomized Pre-Surgical Study Evaluating Anti-PD1 Antibody or Anti-PD1 + Bevacizumab or Anti-PD1 + Anti-CTLA-4 in Patients With Metastatic Renal Cell Carcinoma Who Are Eligible for Cytoreductive Nephrectomy

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Safety and Tolerability of Nivolumab vs. Nivolumab + Bevacizumab vs. Nivolumab + Ipilimumab

Secondary outcome: Immunological Changes in Tumor Tissues

Detailed description: Study Groups: If participant is found to be eligible to take part in this study, they 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. Participant will have an equal chance of being assigned to each group. If participant is in Group N, they will receive nivolumab alone. If participant is in Group N-B, they will receive nivolumab and bevacizumab. If participant is in Group N-I, they will receive nivolumab and ipilimumab. Study Drug Administration: If participant is in Group N, they will receive nivolumab by vein over about 60 minutes on Day 1 of Weeks 1, 3, and 5. Participant will not receive this drug again until Week 14. Starting at Week 14, participant may begin receiving the drug again every 2 weeks. If participant is in Group N-B, they 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. Participant will not receive these drugs again until Week 14. Starting at Week 14, participant may begin receiving nivolumab again every 2 weeks. If participant is in Group N-I, they 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. Participant will not receive these drugs again until Week 14. Starting at Week 14, participant may begin receiving nivolumab again every 2 weeks. Study Visits: If participant is in Group N or Group N-B, on Day 1 of Weeks 1, 3, and 5 or if they are in Group N-I, during Day 1 of Weeks 1 and 4:

- Participant will have a physical exam.

- Participant's blood oxygen level will be tested.

- 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 participant can become pregnant.

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

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

All participants will have the following tests and procedures below: During Week 8:

- Participant will have a physical exam.

- Participant's blood oxygen level will be tested.

- 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.

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

Participant will have surgery on Week 10. During surgery, tumor tissue will be collected for immune system testing. Participant will sign a separate consent explaining the surgery and its risks. If during screening participant was told that they were not eligible to have surgery at Week 10, they will have a biopsy after their last dose of study drug. After Surgery (during Week 14, 15, or 16):

- Participant 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.

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

Length of Study: Participant may continue taking the study drug(s) for up to 2 years after surgery. Participant will no longer be able to take the study drug(s) if the disease gets worse, if intolerable side effects occur, or if they are unable to follow study directions. Patient's participation on the study will be over after the follow-up visits. End-of-Treatment Visit: After participant stops receiving treatment:

- Participant will have a physical exam.

- Participant's blood oxygen level will be tested.

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

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

- If at screening participant was told that they were not eligible to have surgery at

Week 10, they will have a biopsy after their last dose of study drug. Follow-up Visits: About 30 days after participant stops treatment and again around 100 days after that:

- Participant will have a physical exam.

- Participant's blood oxygen level will be tested.

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

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:

- Participant will have a physical exam.

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

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.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): 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, metastasectomy or post-treatment biopsy. Diagnosis must be confirmed by pathologist review of screening biopsy. 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 >/= 15 mm with conventional techniques or >/= 10 mm with more sensitive techniques such as MRI or spiral CT scan. 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, such as Sunitinib, Sorafenib, Pazopanib, Axitinib, Everolimus, and Temsirolimus (but not Bevacizumab) or chemotherapy. 5. ECOG performance status /= 1,500/uL, Platelets >/= 100,000/uL, Hgb > 9. 0 g/dL (may be transfused or receive epoetin alfa [e. g., EpogenĀ®] to maintain or exceed this level), Total bilirubin 40mL/min, AST (SGOT) and/or ALT (SGPT) /= 18 years of age 8. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug. 9. Women must not be breastfeeding 10. WOCBP must agree to follow instructions for method(s) of contraception from the time of enrollment for the duration of treatment with study drug (s) plus 5 half-lives of study drug (s) plus 30 days (duration of ovulatory cycle) for a total of 23 weeks post treatment completion. 11. Men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug (s) plus 5 half-lives of study drug (s) plus 90 days duration of sperm turnover) for a total of 31 weeks post-treatment completion. 12. Azoospermic males and WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However WOCBP must still undergo pregnancy testing as described in these sections. Investigators shall counsel WOCBP and male subjects who are sexually active with WOCBP on the importance of pregnancy prevention and the implications of an unexpected pregnancy Investigators shall advise WOCBP and male subjects who are sexually active with WOCBP on the use of highly effective methods of contraception. Highly effective methods of contraception have a failure rate of < 1% per year when used consistently and correctly. At a minimum, subjects must agree to the use of two methods of contraception, with one method being highly effective and the other method being either highly effective or less effective as listed below: HIGHLY EFFECTIVE METHODS OF CONTRACEPTION: a) Male condoms with spermicide; 13. (Continued from #12) b) Hormonal methods of contraception including combined oral contraceptive pills, vaginal ring, injectables, implants, and intrauterine devices (IUDs) such as Mirena by WOCBP subject or male subject's WOCBP partner.; c) Nonhormonal IUDs, such as ParaGard; d) Tubal ligation; e) Vasectomy; f) Complete Abstinence* *Complete abstinence is defined as complete avoidance of heterosexual intercourse and is an acceptable form of contraception for all study drugs. Abstinence is only acceptable when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (eg, calendar, ovulation, symptothermal, profession of abstinence for entry into a clinical trial, post-ovulation methods) and withdrawal are not acceptable methods of contraception. 14. (Continued from #12) Subjects who choose complete abstinence are not required to use a second method of contraception, but female subjects must continue to have pregnancy tests. Acceptable alternate methods of highly effective contraception must be discussed in the event that the subject chooses to forego complete abstinence. LESS EFFECTIVE METHODS OF CONTRACEPTION: a) Diaphragm with spermicide; b) Cervical cap with spermicide; c) Vaginal sponge; d) Male Condom without spermicide*; e) Progestin only pills by WOCBP subject or male subject's WOCBP partner; f) Female Condom* *A male and female condom must not be used together 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 a major surgical procedure, open biopsy, or significant traumatic injury with poorly healed wound within 6 weeks prior to first dose of study drug; 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 first dose of study drug. 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 history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). Positive test for hepatitis B virus (HBV) using HBV surface antigen (HBV sAg) test or positive test for hepatitis C virus (HCV) using HCV ribonucleic acid (RNA) or HCV antibody test indicating acute or chronic infection. 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 >/= grade 2 proteinuria at baseline routine urinalysis should undergo a 24-hour urine collection, which must be an adequate collection and must demonstrate 140 mmHg and/or diastolic > 90 mmHg). It is permissible to start treatment for hypertension prior to randomization. 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 require ongoing anticoagulation will be excluded. Only aspirin will be permitted. Pre and post-surgical prophylactic anti-coagulation treatment is 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.

Locations and Contacts

Padmanee Sharma, MD, PHD, Phone: 713-792-2830

University of Texas MD Anderson Cancer Center, Houston, Texas 77030, United States; Recruiting
Additional Information

University of Texas MD Anderson Cancer Center Website

Starting date: November 2014
Last updated: August 5, 2015

Page last updated: August 20, 2015

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017