Phase 2 Open-Label, Multi-Center Study to Evaluate the Safety and Efficacy of Sunitinib Malate in Combination With AMG 386 as First Line or Second Line Therapy for Subjects With Metastatic Renal Cell Carcinoma
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Amgen
- Enrollment
- 85
- Primary Endpoint
- Number of Participants With Dose Delays Due to Adverse Events
Study Overview
Brief Summary
This phase 2 study is an open-label, multi-center study to determine the safety and tolerability of AMG 386 in combination with sunitinib in the treatment of subjects with metastatic renal cell carcinoma.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Subjects must have a histologically confirmed metastatic renal cell cancer (RCC) with a clear cell component
- •Low or intermediate risk according to the Memorial Sloan Kettering Cancer Center (MSKCC) prognostic risk classification
- •Measurable disease with at least one unidimensionally measurable lesion per Response Evaluation Criteria in Solid Tumor (RECIST) guidelines with modifications
- •Adequate organ and hematological function as evidenced by laboratory studies conducted at Screening
- •Eastern Cooperative Oncology Group (ECOG) of 0 or 1
Exclusion Criteria
- •Disease related
- •Known history of central nervous system metastases.
- •Previous treatment (excluding surgery, prior cytokine-based immunotherapy and palliative radiotherapy) for advanced or metastatic renal cell carcinoma
- •Focal radiation therapy for palliation of pain from bony metastases within 14 days of enrollment.
- •Medications
- •Currently or previously treated with sunitinib or other small molecule inhibitors of vascular endothelial growth factor (VEGF)
- •Currently or previously treated with agents that neutralizing VEGF
- •Currently or previously treated with AMG 386, or other molecules that inhibit the angiopoietins or Tie2 receptor
- •Currently or previously treated with agents inhibiting the mammalian target of rapamycin (mTOR)
- •Current or within 30 days prior to enrollment treatment with immune modulators
- •Concomitant or previous use within 30 days prior to enrollment of any strong inducer of CYP3A4
- •Concomitant or previous use of amiodarone within 6 months prior to enrollment
- •General medical
- •Clinically significant cardiovascular disease within 12 months prior to enrollment, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication, percutaneous transluminal coronary angioplasty/stent
- •Major surgery within 28 days prior to enrollment or still recovering from prior surgery
- •Uncontrolled hypertension as defined as diastolic > 90 mmHg OR systolic >150 mmHg. The use of anti-hypertensive medications to control hypertension is permitted.
- •Other investigational procedures are excluded
- •Subject currently is enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study(s), or subject is receiving other investigational agent(s)
- •Other inclusion/exclusion criteria may apply, per protocol.
Arms & Interventions
Trebananib 10 mg/kg + Sunitinib
Trebananib 10 mg/kg intravenously (IV) once weekly (QW) plus sunitinib 50 mg orally (PO) once daily (QD) 4 weeks on/2 weeks off
Intervention: Sunitinib (Drug)
Trebananib 10 mg/kg + Sunitinib
Trebananib 10 mg/kg intravenously (IV) once weekly (QW) plus sunitinib 50 mg orally (PO) once daily (QD) 4 weeks on/2 weeks off
Intervention: Trebananib (Drug)
Trebananib 15 mg/kg + Sunitinib
Trebananib 15 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off
Intervention: Sunitinib (Drug)
Trebananib 15 mg/kg + Sunitinib
Trebananib 15 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off
Intervention: Trebananib (Drug)
Outcomes
Primary Outcomes
Number of Participants With Dose Delays Due to Adverse Events
Time Frame: Median treatment duration of trebananib and sunitinib was 316 and 315 days, respectively, for Trebananib 10 mg/kg+Sunitinib, and 393 and 358 days, respectively, for Trebananib 15 mg/kg+Sunitinib.
A trebananib dose was considered delayed if it was administered 11 or more days from the previous trebananib infusion. A sunitinib dose was considered delayed if it was administered 3 or more days from the previous dose, except during holidays.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs)
Time Frame: From first dose of study drug to 30 days after last dose. Median treatment duration of trebananib and sunitinib was 316 and 315 days, respectively, for Trebananib 10 mg/kg+Sunitinib, and 393 and 358 days, respectively, for Trebananib 15 mg/kg+Sunitinib.
AE: any untoward medical occurrence that does not necessarily have a causal relationship with treatment. SAE: an AE that: is fatal; is life threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is an other significant medical hazard. Treatment-emergent AEs (TEAEs) are those that occurred after the first administration of study drug through 30 days after the last study drug administration. Severity was graded according to Common Terminology Criteria (CTCAE) version 3.0, as grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (life-threatening), grade 5 (death).
Number of Participants With Sunitinib Dose Modifications Within 12 Weeks of First Dose
Time Frame: first 12 weeks of study treatment
Participants who had a sunitinib dose modification within 12 weeks from their first dose due to adverse event, laboratory toxicity, or laboratory toxicity and adverse event.
Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values
Time Frame: From first dose of study drug to 30 days after last dose. Median treatment duration of trebananib and sunitinib was 316 and 315 days, respectively, for Trebananib 10 mg/kg+Sunitinib, and 393 and 358 days, respectively, for Trebananib 15 mg/kg+Sunitinib.
Severity was graded according to Common Terminology Criteria (CTCAE) version 3.0, as grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (life-threatening), grade 5 (death).
Secondary Outcomes
- Disease Control Rate (DCR)(48 months after LSE)
- Objective Response Rate (ORR)(48 months after last subject enrolled (LSE))
- Kaplan-Meier Estimate: Duration of Response (DOR)(48 months after LSE)
- Kaplan-Meier Estimate: Overall Survival (OS)(48 months after LSE)
- Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time(Pre-infusion and up to 10 minutes post-infusion on Weeks 1, 4, 7, 10, 13, 22, 34, 46, 58, 70, 82, 94, 106, and safety follow-up (30 ±7 days after the last dose of study drug))
- Pharmacokinetic Parameter: Minimum Observed Concentration (Cmin) for Trebananib Over Time(Pre-infusion on Weeks 4, 7, 10, 13, 22, 34, 46, 58, 70, 82, 94, 106, and safety follow-up (30 ±7 days after the last dose of study drug))
- Pharmacokinetic Parameter: Cmin for Sunitinib Over Time(Pre-infusion on Weeks 4, 7, 10, 16, 22, 34, 46, 58, 70, 82, 94, 106, and safety follow-up (30 ±7 days after the last dose of study drug))
- Kaplan-Meier Estimate: Progression Free Survival (PFS)(48 months after LSE)
- Maximum Percent Reduction From Baseline in the Sum of the Longest Diameters (SLD) of Target Lesions From Baseline to Post-Baseline Nadir(Baseline, 48 months after LSE)
- Pharmacokinetic Parameter: Cmin for Sunitinib Metabolite Over Time(Pre-infusion on Weeks 4, 7, 10, 16, 22, 34, 46, 58, 70, 82, 94, 106, and safety follow-up (30 ±7 days after the last dose of study drug))
- Number of Participants Binding Antibody- or Neutralizing Antibody-Positive Post-Baseline(48 months after LSE)