Clinical trial NCT00853372: AMG 386 Phase 2 Open-Label Renal Cell Carcinoma (RCC) Study 1st Line or After Cytokine Failure in Combination With Sunitinib
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Advanced Renal Cell Carcinoma
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2009-03-02
Enrollment: 85
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

* 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.

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs)
timeFrame: 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.
measure: Number of Participants With Dose Delays Due to Adverse Events
timeFrame: 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.
measure: Number of Participants With Sunitinib Dose Modifications Within 12 Weeks of First Dose
timeFrame: first 12 weeks of study treatment
measure: Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values
timeFrame: 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.
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: 48 months after last subject enrolled (LSE)
measure: Kaplan-Meier Estimate: Duration of Response (DOR)
timeFrame: 48 months after LSE
measure: Disease Control Rate (DCR)
timeFrame: 48 months after LSE
measure: Kaplan-Meier Estimate: Progression Free Survival (PFS)
timeFrame: 48 months after LSE
measure: Kaplan-Meier Estimate: Overall Survival (OS)
timeFrame: 48 months after LSE
measure: Maximum Percent Reduction From Baseline in the Sum of the Longest Diameters (SLD) of Target Lesions From Baseline to Post-Baseline Nadir
timeFrame: Baseline, 48 months after LSE
measure: Pharmacokinetic Parameter: Maximum Observed Concentration (Cmax) for Trebananib Over Time
timeFrame: 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)
measure: Pharmacokinetic Parameter: Minimum Observed Concentration (Cmin) for Trebananib Over Time
timeFrame: 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)
measure: Pharmacokinetic Parameter: Cmin for Sunitinib Over Time
timeFrame: 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)
measure: Pharmacokinetic Parameter: Cmin for Sunitinib Metabolite Over Time
timeFrame: 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)
measure: Number of Participants Binding Antibody- or Neutralizing Antibody-Positive Post-Baseline
timeFrame: 48 months after LSE
Other outcomes:
Locations:
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Atkins MB, Gravis G, Drosik K, Demkow T, Tomczak P, Wong SS, Michaelson MD, Choueiri TK, Wu B, Navale L, Warner D, Ravaud A. Trebananib (AMG 386) in Combination With Sunitinib in Patients With Metastatic Renal Cell Cancer: An Open-Label, Multicenter, Phase II Study. J Clin Oncol. 2015 Oct 20;33(30):3431-8. doi: 10.1200/JCO.2014.60.6012. Epub 2015 Aug 24.