Nivolumab With or Without Bevacizumab or Ipilimumab Before Surgery in Treating Patients With Metastatic Kidney Cancer That Can Be Removed by Surgery

NCT02210117 | Active Not Recruiting Early Phase 1 FDA Drug

• 2 other identifiers: 2013-0715NCI-2014-01857
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized pilot early phase I trial studies the side effects and how well nivolumab alone works compared to nivolumab with bevacizumab or ipilimumab before surgery in treating patients with kidney cancer, also referred to as renal cell cancer, that has spread to another place in body and can be removed by surgery. Immunotherapy with monoclonal antibodies, such as nivolumab, bevacizumab, and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Conditions

Clear Cell Renal Cell Carcinoma; Metastatic Kidney Carcinoma; Stage IV Renal Cell Cancer AJCC v7

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events, defined any grade 3 or higher adverse event that is possibly, probably, or definitely related to any therapy received on this protocol

  Descriptive statistical analyses will be performed to summarize the overall toxicity rate and individual adverse event rates including summary tables, scatter-plots, box-plots, proportions, median, means, and standard deviations.

  6 weeks

Secondary Outcomes (5)

• Immunological changes in tumor tissues and peripheral blood

  Baseline to up to week 4

• Objective response rates

  Up to 5 years

• Duration of response

  Up to 5 years

• Progression-free survival

  Up to 5 years

• Overall survival

  Up to 5 years

Study Arms (3)

Arm A (nivolumab, surgery)

EXPERIMENTAL

Patients receive nivolumab IV over 60 minutes on day 1 every 2 weeks for 6 weeks. Approximately 4 weeks later, patients undergo nephrectomy, metastasectomy or biopsy. Beginning 4-6 weeks after surgery, patients in all arms who have clinical response, stable disease, or even slight progression of disease to therapy preoperatively, receive maintenance nivolumab IV over 60 minutes on day 1. Cycles repeat every 4 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

Procedure: Biopsy; Other: Laboratory Biomarker Analysis; Procedure: Metastasectomy; Biological: Nivolumab; Procedure: Therapeutic Conventional Surgery

Arm B (nivolumab, bevacizumab, surgery)

EXPERIMENTAL

Patients receive nivolumab IV over 60 minutes and bevacizumab IV over 90 minutes on day 1 every 2 weeks for 6 weeks. Patients also undergo nephrectomy, metastasectomy or biopsy as in Arm A. Beginning 4-6 weeks after surgery, patients in all arms who have clinical response, stable disease, or even slight progression of disease to therapy preoperatively, receive maintenance nivolumab IV over 60 minutes on day 1. Cycles repeat every 4 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

Biological: Bevacizumab; Procedure: Biopsy; Other: Laboratory Biomarker Analysis; Procedure: Metastasectomy; Biological: Nivolumab; Procedure: Therapeutic Conventional Surgery

Arm C (nivolumab, ipilimumab, surgery)

EXPERIMENTAL

Patients receive nivolumab IV over 60 minutes and ipilimumab IV over 90 minutes on day 1 every 3 weeks for 6 weeks. Patients also undergo nephrectomy, metastasectomy or biopsy as in Arm A. Beginning 4-6 weeks after surgery, patients in all arms who have clinical response, stable disease, or even slight progression of disease to therapy preoperatively, receive maintenance nivolumab IV over 60 minutes on day 1. Cycles repeat every 4 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

Procedure: Biopsy; Biological: Ipilimumab; Other: Laboratory Biomarker Analysis; Procedure: Metastasectomy; Biological: Nivolumab; Procedure: Therapeutic Conventional Surgery

Interventions

Bevacizumab BIOLOGICAL

Given IV

Also known as: Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin, Bevacizumab Biosimilar BEVZ92, Bevacizumab Biosimilar BI 695502, Bevacizumab Biosimilar CBT 124, Bevacizumab Biosimilar FKB238, Bevacizumab Biosimilar MIL60, Bevacizumab Biosimilar QL 1101, BEVACIZUMAB, LICENSE HOLDER UNSPECIFIED, Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer, Recombinant Humanized Anti-VEGF Monoclonal Antibody, rhuMab-VEGF

Arm B (nivolumab, bevacizumab, surgery)

Biopsy PROCEDURE

Undergo biopsy

Also known as: Bx

Arm A (nivolumab, surgery); Arm B (nivolumab, bevacizumab, surgery); Arm C (nivolumab, ipilimumab, surgery)

Ipilimumab BIOLOGICAL

Given IV

Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4, Yervoy

Arm C (nivolumab, ipilimumab, surgery)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm A (nivolumab, surgery); Arm B (nivolumab, bevacizumab, surgery); Arm C (nivolumab, ipilimumab, surgery)

Metastasectomy PROCEDURE

Undergo metastasectomy

Arm A (nivolumab, surgery); Arm B (nivolumab, bevacizumab, surgery); Arm C (nivolumab, ipilimumab, surgery)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Arm A (nivolumab, surgery); Arm B (nivolumab, bevacizumab, surgery); Arm C (nivolumab, ipilimumab, surgery)

Therapeutic Conventional Surgery PROCEDURE

Undergo nephrectomy

Arm A (nivolumab, surgery); Arm B (nivolumab, bevacizumab, surgery); Arm C (nivolumab, ipilimumab, surgery)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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
• Patients must have measurable disease and is defined as a lesion that can be accurately measured on the long axis with a minimum size of 10 mm or a lymph node that can be accurately measured along the short axis of a minimum size of 15 mm (computed tomography \[CT\] scan slice thickness can be no greater than 5 mm)
• Patients can have had prior treatment for RCC including prior surgery, radiation therapy, immunotherapy with interleukin (IL)-2 or interferon (but not anti-programmed cell death \[PD\]1 or anti-cytotoxic T-lymphocyte-associated protein 4 \[CTLA-4\]), target therapy with receptor tyrosine kinase (RTK) inhibitors/mammalian target of rapamycin (mTOR) inhibitors, such as sunitinib, sorafenib, pazopanib, axitinib, everolimus, and temsirolimus (but not bevacizumab) or chemotherapy
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
• Absolute neutrophil count \>= 1,500/uL within 14 days of the first dose of study drug
• Platelets \>= 100,000/uL within 14 days of the first dose of study drug
• Hemoglobin (Hgb) \> 9.0 g/dL (may be transfused or receive epoetin alfa \[e.g., Epogen\] to maintain or exceed this level) within 14 days of the first dose of study drug
• Total bilirubin =\< 1.5 mg/dl within 14 days of the first dose of study drug
• Serum creatinine =\< 1.5 times the upper limit of normal or estimated creatinine clearance (CrCl) \> 40 mL/min within 14 days of the first dose of study drug
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and/or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 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 within 14 days of the first dose of study drug
• Mild autoimmune conditions (such as localized psoriasis) requiring minimal treatment or systemic autoimmune conditions well controlled by target agents such as an anti-IL-17 that do not affect overall immune system
• Patients with a history of Hashimoto's thyroiditis only requiring hormone replacement, type I diabetes, or conditions not expected to recur in the absence of an external trigger are allowed to participate
• Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) within 24 hours prior to the start of study drug
• Women must not be breastfeeding

You may not qualify if:

• 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
• Patients who have organ allografts
• 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
• Known or suspected 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 \[e.g., Wegener's granulomatosis\]) are excluded from this study; any condition requiring systemic treatment with corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to first dose of study drug; inhaled steroids and adrenal replacement steroids doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
• 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
• 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
• Patients who have had a history of acute diverticulitis, abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, gastrointestinal (GI) obstruction, abdominal carcinomatosis which are known risks factors for bowel perforation, should be excluded from the study
• 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
• 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
• 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
• 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 =\< 1 g of protein/24 hour (hr) to allow participation in the study
• Patients who have uncontrolled hypertension (systolic \> 140 mmHg and/or diastolic \> 90 mmHg); it is permissible to start treatment for hypertension prior to randomization
• Patients who are on high dose steroid (e.g. \> 10 mg prednisone daily or equivalent) or other more potent immune suppression medications (e.g. infliximab)
• Patients who have had flu, hepatitis, or other vaccines within a month prior to initiation of study drugs
• Patients who have clinical history of coagulopathy, bleeding diathesis or thrombosis within the past year

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Bevacizumab; Immunoglobulin G; Disulfides; Biopsy; Ipilimumab; CTLA-4 Antigen; Metastasectomy; Nivolumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunoglobulin Isotypes; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers

Study Officials

• Padmanee Sharma

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2014
• First Posted: August 6, 2014
• Study Start: November 25, 2014
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): November 30, 2026
• Last Updated: January 7, 2026

Record last verified: 2026-01

Locations

US (1)