Study of Optimized Management of Nivolumab Based on Response in Patients With Advanced RCC (OMNIVORE Study)

NCT ID: NCT03203473

Last Updated: 2025-04-02

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 85 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-26
• Study Completion Date: 2025-12-28

Brief Summary

This research study is studying two drugs at different time points as a possible treatment for advanced renal cell cancer

The drugs involved in this study are:

Nivolumab Ipilimumab

Detailed Description

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of investigational drugs to learn whether the drugs work in treating a specific disease. "Investigational" means that the intervention is being studied.

Nivolumab and ipilimumab are antibodies (a type of human protein) that work to stimulate your body's immune system to fight tumor cells. The FDA (the U.S. Food and Drug Administration) has approved nivolumab as a treatment option for this disease; however, the FDA has not approved the way nivolumab and ipilimumab are being administered in this study. Ipilimumab is FDA approved for the treatment of melanoma (skin cancer) and has been previously studied in renal cell cancer.

This study is being done to evaluate nivolumab treatment strategies based on each patients individual response to treatment. In participants who have a response to treatment, nivolumab will be stopped and participants will be closely monitored. In participants who do not have a response to treatment,the investigators will investigate whether the addition of ipilimumab improves a participant response to treatment. Participant blood and tissue samples will be collected to learn about how certain biomarkers and genes relate to participant outcomes.

Conditions

Renal Cancer

Study Design

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

Study Groups

Overall cohort: Initial Primary Treatment with Nivolumab (induction phase)

• Therapy with nivolumab IV every 2 weeks
• Serial imaging assessments every 8 weeks
• After confirmatory scans, patients are assigned to Arm A or Arm B.

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

Nivolumab binds to and blocks the activation of PD-1, an Ig superfamily transmembrane protein, by its ligands programmed cell death ligand 1 (PD-L1), overexpressed on certain cancer cells, and programmed cell death ligand 2 (PD-L2), which is primarily expressed on APCs

Arm A: Observation Arm (for patients with persistent response to induction nivolumab)

Patients with persistent response (complete or partial response) to induction nivolumab are assigned to Arm A (Observation Arm).

• Patients discontinued nivolumab after allocation to Arm A.
• Serial imaging assessments every 8 weeks.
• If scans persistently show PR/CR, patients remained on observation.
• If progressive disease develops, therapy with nivolumab (480 mg IV every 4 weeks) will be resumed.
• If there is subsequent progression on nivolumab monotherapy, ipilimumab (1 mg/kg IV every 3 weeks x 2 doses) is added.
• If progression after nivolumab + ipilimumab, therapy discontinued. If SD/PR/CR, nivolumab is continued until progression.

Group Type: EXPERIMENTAL

Ipilimumab

Intervention Type: DRUG

YERVOY is thought to work with the body's immune system to increase the activity of T cells and cause the body to attack cancer cells

Nivolumab

Intervention Type: DRUG

Nivolumab binds to and blocks the activation of PD-1, an Ig superfamily transmembrane protein, by its ligands programmed cell death ligand 1 (PD-L1), overexpressed on certain cancer cells, and programmed cell death ligand 2 (PD-L2), which is primarily expressed on APCs

Arm B: Nivolumab+Ipilimumab then nivolumab alone (for patients with SD/PD to induction nivolumab)

Patients with confirmed SD/PD to induction nivolumab are allocated to Arm B (Combination Therapy Arm).

• In combination therapy, patients received nivolumab 3 mg/kg and ipilimumab 1 mg/kg intravenously every 3 weeks for two doses.
• After then nivolumab will be continued at 480 mg IV every 4 weeks until disease progression.
• Arm B patients undergo imaging at 12 weeks and then every 8 weeks.

Group Type: EXPERIMENTAL

Ipilimumab

Intervention Type: DRUG

YERVOY is thought to work with the body's immune system to increase the activity of T cells and cause the body to attack cancer cells

Nivolumab

Intervention Type: DRUG

Nivolumab binds to and blocks the activation of PD-1, an Ig superfamily transmembrane protein, by its ligands programmed cell death ligand 1 (PD-L1), overexpressed on certain cancer cells, and programmed cell death ligand 2 (PD-L2), which is primarily expressed on APCs

Interventions

Ipilimumab

YERVOY is thought to work with the body's immune system to increase the activity of T cells and cause the body to attack cancer cells

Intervention Type: DRUG

Nivolumab

Nivolumab binds to and blocks the activation of PD-1, an Ig superfamily transmembrane protein, by its ligands programmed cell death ligand 1 (PD-L1), overexpressed on certain cancer cells, and programmed cell death ligand 2 (PD-L2), which is primarily expressed on APCs

Intervention Type: DRUG

Other Intervention Names

Yervoy; Opdivo

Eligibility Criteria

Exclusion Criteria

• Subjects meeting any of the criteria below may not participate in the study:
• Prior use of systemic checkpoint inhibitors for the management of metastatic RCC is excluded. Prior IFN-α or IL-2 is allowed.
• Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitors) within 2 weeks of enrollment or receipt of any anti-cancer therapy (including investigational therapy, monoclonal antibodies, cytokine therapy) within 4 weeks of enrollment.
• Treatment with systemic immunosuppressive medications including but not limited to:
• prednisone, dexamethasone, cyclosporin, azathioprine, methotrexate, thalidomide, anti- tumor necrosis factor (TNF) agents within 2 weeks of first study dose.
• Subjects who have received acute, low-dose systemic immunosuppressant medications may be enrolled (such as steroids for acute nausea or cancer-related pain ≤ 10 mg prednisone) may be enrolled sooner than 2 weeks of first study dose.
• Subjects with adrenal insufficiency on physiologic replacement doses of steroids may be enrolled (≤ 10 mg prednisone).
• The use of inhaled, topical, ocular or intra-articular corticosteroids and mineralocorticoids are allowed.
• Treatment with a receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor (e.g. denosumab) within 2 weeks of first study dose.
• Radiotherapy for RCC within 14 days of first study treatment with the exception of a single fraction of radiation administered for palliation of symptoms.
• Known active metastases to the brain, spinal cord or leptomeninges unless adequately treated with radiotherapy, radiosurgery, or surgery and stable for at least 4 weeks of first study treatment as documented by magnetic resonance imaging (MRI) or computerized tomography (CT) imaging and having no ongoing requirement for steroids.
• Malignancies other than RCC within 5 years of first study treatment with the exception of those with negligible risk of metastases or death and/or treated with expected curative outcome (carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer, ductal carcinoma in situ of the breast, non-muscle invasive urothelial carcinoma).
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion protein.
• Known hypersensitivity to any component of the nivolumab or ipilimumab product.
• Any active or recent history (within 6 months of first study dose) of autoimmune disease or syndrome that requires systemic corticosteroids (>10 mg daily prednisone equivalent) or immunosuppressive medications including but not limited to: myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid syndrome, Wegner's granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. Subjects with vitiligo, controlled type I diabetes mellitus, hypo- or hyperthyroid disease, or surgical adrenal insufficiency requiring hormone replacement therapy are permitted to enroll.
• Any condition requiring treatment with corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medication within 14 days of the first dose of study drug. Inhaled, topical, ocular or intra-articular steroids and adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• Uncontrolled adrenal insufficiency.
• History of idiopathic pulmonary fibrosis, organized pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening imaging CT of the chest. History of radiation pneumonitis in the radiation field is permitted.
• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome.
• Known active or chronic hepatitis B infection (defined as having a positive hepatitis B surface antigen (HBsAg) test at screening). Subject with past or resolved hepatitis B infection (defined as having a negative HBsAg test and positive antibody to hepatitis B core antigen test) are eligible. Hepatitis B viral DNA must be obtained in subjects with positive hepatitis B core antibody prior to first treatment start.
• Active hepatitis C infection. Subjects positive hepatitis C antibody test are eligible if PCR is negative for hepatitis C viral DNA.
• Severe infections within 4 weeks of first study treatment including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.
• Receipt of therapeutic oral or IV antibiotics within 2 weeks of first study treatment. Subjects receiving routine antibiotic prophylaxis (for dental extractions/procedures) are eligible.
• Significant cardiovascular disease such as New York Heart Association (NYHA) class III or greater, myocardial infarction within the previous 3 months, unstable arrhythmias, unstable angina. Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction < 45% must be on a stable regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist when appropriate.
• Prolonged corrected QT interval by the Fridericia correction formula (QTcF) on screening EKG > 500 msec.
• History of abdominal or tracheoesophageal fistula or GI perforation within 6 months of first study treatment.
• Clinical signs or symptoms of GI obstruction or requirement of routine parenteral nutrition.
• Evidence of abdominal free air not explained by paracentesis or recent surgical procedure.
• Serious, non-healing or dehiscing wound or active ulcer
• Major surgical procedure within 4 weeks of first study treatment.
• Presence of any toxicities attributed to prior anti-cancer therapy that are not resolved to grade 1 (National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0) or baseline before administration of study drug.
• Prior allogenic stem cell or solid organ transplant.
• Administration of a live, attenuated vaccine within 4 weeks for first study treatment.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Toni Choueiri, MD

OTHER

Sponsor Role: lead

Responsible Party

Toni Choueiri, MD

Sponsor Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Toni K Choueiri, MD

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

University of California, San Diego Moores Cancer Center

La Jolla, California, United States

University of Chicago Medical Center

Chicago, Illinois, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Lifespan Comprehensve Cancer Center

Providence, Rhode Island, United States

University of Utah, Huntsman Cancer Center

Salt Lake City, Utah, United States

Unviersity of Wisconsin Carbone Cancer Center

Madison, Wisconsin, United States

Countries

United States

References

Bootsma M, McKay RR, Emamekhoo H, Bade RM, Schehr JL, Mannino MC, Singh A, Wolfe SK, Schultz ZD, Sperger J, Xie W, Signoretti S, Kyriakopoulos CE, Kosoff D, Abel EJ, Helzer KT, Rydzewski N, Bakhtiar H, Shi Y, Blitzer G, Bassetti M, Floberg J, Yu M, Sethakorn N, Sharifi M, Harari PM, Choueiri TK, Lang JM, Zhao SG. Longitudinal Molecular Profiling of Circulating Tumor Cells in Metastatic Renal Cell Carcinoma. J Clin Oncol. 2022 Nov 1;40(31):3633-3641. doi: 10.1200/JCO.22.00219. Epub 2022 May 26.

Reference Type: DERIVED

PMID: 35617646 (View on PubMed)

Bade RM, Schehr JL, Emamekhoo H, Gibbs BK, Rodems TS, Mannino MC, Desotelle JA, Heninger E, Stahlfeld CN, Sperger JM, Singh A, Wolfe SK, Niles DJ, Arafat W, Steinharter JA, Jason Abel E, Beebe DJ, Wei XX, McKay RR, Choueri TK, Lang JM. Development and initial clinical testing of a multiplexed circulating tumor cell assay in patients with clear cell renal cell carcinoma. Mol Oncol. 2021 Sep;15(9):2330-2344. doi: 10.1002/1878-0261.12931. Epub 2021 Mar 3.

Reference Type: DERIVED

PMID: 33604999 (View on PubMed)

McKay RR, McGregor BA, Xie W, Braun DA, Wei X, Kyriakopoulos CE, Zakharia Y, Maughan BL, Rose TL, Stadler WM, McDermott DF, Harshman LC, Choueiri TK. Optimized Management of Nivolumab and Ipilimumab in Advanced Renal Cell Carcinoma: A Response-Based Phase II Study (OMNIVORE). J Clin Oncol. 2020 Dec 20;38(36):4240-4248. doi: 10.1200/JCO.20.02295. Epub 2020 Oct 27.

Reference Type: DERIVED

PMID: 33108238 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

17-064

Identifier Type: -

Identifier Source: org_study_id