AMG 386 Phase 2 Open-Label Renal Cell Carcinoma (RCC) Study 1st Line or After Cytokine Failure in Combination With Sunitinib

NCT00853372 | Completed Phase 2 Results

• 1 other identifier: 20080579
• Study Type: interventional
• Target: 85
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Advanced Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (4)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations (DCs) Due to Adverse Events (AEs)

  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).

  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.

• Number of Participants With Dose Delays Due to Adverse Events

  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.

  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.

• Number of Participants With Sunitinib Dose Modifications Within 12 Weeks of First Dose

  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.

  first 12 weeks of study treatment

• Number of Participants With Worst Post-Baseline Grade 3 or Higher Toxicity in Laboratory Values

  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).

  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 (11)

• Objective Response Rate (ORR)

  48 months after last subject enrolled (LSE)

• Kaplan-Meier Estimate: Duration of Response (DOR)

  48 months after LSE

• Disease Control Rate (DCR)

  48 months after LSE

• Kaplan-Meier Estimate: Progression Free Survival (PFS)

  48 months after LSE

• Kaplan-Meier Estimate: Overall Survival (OS)

  48 months after LSE

Study Arms (2)

Trebananib 10 mg/kg + Sunitinib

EXPERIMENTAL

Trebananib 10 mg/kg intravenously (IV) once weekly (QW) plus sunitinib 50 mg orally (PO) once daily (QD) 4 weeks on/2 weeks off

Drug: Sunitinib; Drug: Trebananib

Trebananib 15 mg/kg + Sunitinib

EXPERIMENTAL

Trebananib 15 mg/kg IV QW plus sunitinib 50 mg PO QD 4 weeks on/2 weeks off

Drug: Sunitinib; Drug: Trebananib

Interventions

Sunitinib DRUG

Sunitinib will be administered 50 mg QD and is considered to be the background therapy as it is licensed for treatment of reneal cell cancer (RCC) and will be administered to all participants.

Also known as: SUTENT (oral multi-kinase inhibitor)

Trebananib 10 mg/kg + Sunitinib; Trebananib 15 mg/kg + Sunitinib

Trebananib DRUG

Administered until a participant develops disease progression, clinical progression, unacceptable toxicity, withdraws consent, or death.

Also known as: AMG 386, Angiogenesis inhibitor

Trebananib 10 mg/kg + Sunitinib; Trebananib 15 mg/kg + Sunitinib

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Related Publications (1)

• 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.

  PMID: 26304872 DERIVED

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Interventions

Sunitinib; trebananib; Angiogenesis Inhibitors

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Growth Inhibitors; Antineoplastic Agents; Therapeutic Uses

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2009
• First Posted: March 2, 2009
• Study Start: May 28, 2009
• Primary Completion: August 8, 2011
• Study Completion: June 25, 2019
• Last Updated: July 1, 2020
• Results First Posted: July 1, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.