NCT02348008

Phase Ib and Phase II Studies of MK-3475 in Combination + for Renal Cell Carcinoma:

Phase Ib and Phase II Studies of Anti-PD-1 Antibody MK-3475 in Combination With Bevacizumab for the Treatment of Metastatic Renal Cell Carcinoma: Big Ten Cancer Research Consortium GU14-003

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 61 (actual)
• Sponsor: Arkadiusz Z. Dudek, MD · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is an open label, multi-institutional, single arm study of dose escalation phase Ib cohort, followed by a phase II cohort of anti-PD-1 antibody MK-3475 in combination with bevacizumab. No randomization or blinding is involved.

Detailed description

OUTLINE: This is a multi-center study. The phase Ib dose escalation study will evaluate MK-3475 in combination with bevacizumab in subjects with metastatic clear cell renal carcinoma after failure of at least one systemic therapy for metastatic disease. The phase II trial will determine the activity of the combination of MK-3475 and bevacizumab in first line therapy for subjects with metastatic clear cell renal carcinoma. PHASE Ib DOSE ESCALATION INVESTIGATIONAL TREATMENT: Cohort 1 will consist of 3-6 patients who will receive MK-3475 200mg and bevacizumab 10mg on day 1 of the 21-day cycle. The drugs are administered 15-30 minutes apart in separate intravenous infusions. Cohort 2 will consist of 3-9 patients who will receive MK-3475 200mg and bevacizumab 15mg on day 1 of the 21-day cycle. The drugs are administered 15-30 minutes apart in separate intravenous infusions. If none of the 3 subjects experience a dose limiting toxicity (DLT) during the first cycle of therapy, an additional 3 subjects will be enrolled at dose level 2. If all three subjects in dose level 2 complete the first cycle of therapy without DLT, 3 more subjects will be enrolled to ensure only 0-1 of 6 subjects have a DLT. There will be no further escalation beyond dose level 2. PHASE II INVESTIGATIONAL TREATMENT: The maximum safe dose of MK-3475 in combination bevacizumab (as determined in the phase 1b cohort) will be given on day 1 of each 21 day cycle. Treatment will continue until disease progression, unacceptable toxicity, subject refusal, or subject death either from progression of disease, the therapy itself, or from other causes. Subjects who voluntarily stop the study, have progressive disease, or unacceptable toxicities will be followed for a total of 24 months. Karnofsky Performance Status (KPS) ≥ 70% within 28 days prior to registration for protocol therapy. Life Expectancy: 6 months or greater The following baseline labs must be completed within 28 days prior to registration for protocol therapy: Hematopoietic: * Absolute neutrophil count (ANC) ≥ 1.5 × 10 9/L * Platelets ≥ 100 × 10 9/L * Hemoglobin (Hgb) ≥ 9.0 g/dL Renal: * Serum creatinine ≤ 1.5 × upper limit of normal (ULN) * OR, if serum creatinine \> 1.5 × ULN, estimated glomerular filtration rate (eGFR) ≥ 40 mL/min Hepatic: * Total serum bilirubin ≤ 1.5 × ULN * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN * OR, AST and ALT ≤ 5 × ULN if liver function abnormalities are due to underlying malignancy Coagulation: * INR \< 1.5 × ULN * OR for subjects receiving warfarin or LMWH, the subjects must, in the investigator's opinion, be clinically stable with no evidence of active bleeding while receiving anticoagulant therapy. The INR for these subjects may exceed 1.5 × ULN if that is the goal of anticoagulant therapy.

Conditions

• Clear Cell Renal Carcinoma

Interventions

Type	Name	Description
DRUG	MK-3475	Arm A: Phase 1b Cohort 1: 200mg IV; Arm A: Phase 1b Cohort 2: 200mg IV
DRUG	Bevacizumab	Arm A: Phase 1b Cohort 1: 10mg IV; Arm A: Phase 1b Cohort 2: 15mg IV
DRUG	MK-3475	Arm B: Phase II Treatment: 200mg IV
DRUG	Bevacizumab	Arm B: Phase II Treatment: administered at the maximum safe dose of 10mg or 15mg as established in the Phase 1b dose escalation cohort study.

Timeline

• Start date: 2015-03-01
• Primary completion: 2019-12-05
• Completion: 2019-12-05
• First posted: 2015-01-28
• Last updated: 2022-09-14
• Results posted: 2020-07-31

Locations

9 sites across 1 country: United States