Study of Dalantercept and Axitinib in Patients With Advanced Renal Cell Carcinoma

NCT ID: NCT01727336

Last Updated: 2022-10-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-31
• Study Completion Date: 2017-11-30

Brief Summary

The purpose of Part 1 of this study is to evaluate the safety and tolerability of dalantercept in combination with axitinib in patients with advanced renal cell carcinoma (RCC) to determine the recommended dose level of dalantercept in combination with axitinib for Part 2.

The purpose of Part 2 of this study is to determine whether treatment with dalantercept in combination with axitinib prolongs progression free survival (PFS) compared to axitinib alone in patients with advanced renal cell carcinoma (RCC).

Detailed Description

In Part 1 of the study, groups of subjects received escalating doses of dalantercept; 0.6, 0.9 and 1.2 mg/kg in sequential groups. All subjects received concurrent axitinib 5 mg PO BID. A total of 29 subjects were enrolled i Part 1 of the study.

In Part 2, dalantercept at 0.9 mg/kg once every 3 weeks plus axitinib 5 mg PO BID was compared to placebo plus axitinib 5 mg PO BID. A total of 131 subjects were enrolled in Part 2 for a total of 160 in the study

Conditions

Advanced Renal Cell Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Dalantercept 0.9 mg/kg plus axitinib

Subcutaneous (SC) injection of dalantercept 0.9 mg/kg once every 3 weeks and oral axitinib 5 mg BID for continuous dosing.

Group Type: EXPERIMENTAL

Dalantercept and axitinib

Intervention Type: DRUG

Placebo plus axitinib

Subcutaneous injection of normal saline once every 3 weeks and oral axitinib 5 mg BID for continuous dosing

Group Type: PLACEBO_COMPARATOR

Placebo and axitinib

Intervention Type: DRUG

Dalantercept 0.6 mg/kg

Part 1 dose escalation arm 0.6 mg/kg dalantercept once every 3 weeks

Group Type: EXPERIMENTAL

Dalantercept and axitinib

Intervention Type: DRUG

Dalantercept 0.9 mg/kg

Part 1 dose escalation arm 0.9 mg/kg dalantercept once every 3 weeks

Group Type: EXPERIMENTAL

Dalantercept and axitinib

Intervention Type: DRUG

Dalantercept 1.2 mg/kg

Part 1 dose escalation arm 1.2 mg/kg dalantercept once every 3 weeks

Group Type: EXPERIMENTAL

Dalantercept and axitinib

Intervention Type: DRUG

Dalantercept 1.5 mg/kg

Part 1 dose escalation arm 1.5 mg/kg dalantercept once every 3 weeks

Group Type: EXPERIMENTAL

Dalantercept and axitinib

Intervention Type: DRUG

Interventions

Dalantercept and axitinib

Intervention Type: DRUG

Placebo and axitinib

Intervention Type: DRUG

Other Intervention Names

ACE-041, Inlyta; Inlyta

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed, advanced, predominantly clear cell renal cell carcinoma (RCC).
• Part 1: Progression of disease following up to three lines of prior therapy, including at least one approved VEGF receptor tyrosine kinase inhibitor for RCC. Adjuvant therapy is permitted as one line of prior therapy.
• Part 2: Progression of disease following one VEGF pathway inhibitor for RCC (e.g. sunitinib, pazopanib, sorafenib, bevacizumab, tivozanib, or cabozantinib) inclusive of adjuvant therapy if there was documented disease progression during treatment. Patients may have received one additional line of an approved mTOR kinase inhibitor (e.g. everolimus, temsirolimus). Prior exposure to investigational and/or approved anticancer immune therapies is permitted.
• A minimum of 1 week since the last dose of prior therapy (a minimum of 4 weeks since anticancer immune therapy or bevacizumab +/- interferon).
• Measurable disease that is evaluable by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy of at least 12 weeks.
• Clinical laboratory values within acceptable ranges within 72 hours prior to study day 1.

Exclusion Criteria

• Clinically significant organ/system disease unrelated to RCC that in the judgment of the investigator should preclude treatment with dalantercept or axitinib.
• Clinically significant cardiovascular risk.
• Known CNS metastases or leptomeningeal disease:

For Part 1, patients with CNS metastases treated with whole brain radiotherapy, gamma knife, and/or surgery who are considered stable by CNS imaging and are not being treated with corticosteroids 6 weeks prior to study day 1 may be enrolled.

For Part 2, patients with CNS metastases treated stereotactic radio-surgery (SRS), and/or surgery who are considered stable by CNS imaging for at least 2 months prior to enrollment and are not being treated with corticosteroids 6 weeks prior to study day 1 may be enrolled.

• Any active malignancy, other than RCC, for which chemotherapy or other anti-cancer therapy is indicated. Patients with adequately treated non-melanoma skin cancer, in situ cancer, or other cancer from which the subject has been disease-free for at least 3 years will be permitted.
• Any lesion invading or having encasement ≥ 180 degrees around the wall of a major blood vessel as assessed by computed tomography (CT) scan and/or magnetic resonance imaging (MRI).
• Radiotherapy within 2 weeks prior to study day 1.
• Lack of recovery from toxic effects of previous treatment for RCC ≤ grade 1 with the exception of alopecia, unless stabilized under adequate medical control.
• Patients undergoing renal dialysis.
• Major surgery within 4 weeks prior to study day 1 (patients must have recovered completely from any previous surgery prior to study day 1).
• Any active infection requiring antibiotic therapy within 2 weeks of study day 1.
• Anti-coagulation therapy. Aspirin, other anti-platelet agents, and low molecular weight heparin are permitted unless the investigator deems the patient is at a significant risk for bleeding.
• Current use or anticipated inability to avoid potent CYP3A4/5 inhibitors or inducers (please refer to the Inlyta® [axitinib] prescribing information) during participation in the study.
• Peripheral edema requiring medical intervention within 2 weeks prior to study day 1.
• Bleeding diathesis including clinically significant platelet disorders or active hemoptysis (defined as bright red blood of ≥ 1/2 teaspoon [2.5 mL] in any 24 hour period) within 6 months prior to study day 1. For clinically significant epistaxis within 4 weeks prior to study day 1, no risk of further bleeding must be clearly documented.
• Known history of hereditary hemorrhagic telangiectasia (HHT).
• Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infections or positive human immunodeficiency virus (HIV) antibody results. Patients with sustained virologic response to HCV treatment or immunity to HBV from prior infection without cirrhosis may be included.
• History of severe (defined as ≥ grade 3, using the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 4.0 [NCI-CTCAE] v4 current active minor version) allergic or anaphylactic reaction or hypersensitivity to recombinant proteins or excipients (10 mM Tris buffered saline) in the investigational agent.
• Any prior treatment with dalantercept or any other agent targeting ALK1 pathway.
• Any prior treatment with axitinib.
• A morbidity (per the prescribing information) that would require starting a patient at a reduced dose of axitinib.
• Treatment with another investigational drug (with the exception of anticancer immune therapy) or device, or approved therapy for investigational use, within 5 times the half-life of the drug or within 3 weeks prior to study day 1 if the half life is not known.
• Pregnant or lactating female patients.

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

Sponsors

Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Arizona Oncology Associates, PC - HOPE

Tucson, Arizona, United States

Highlands Oncology Group, PA

Fayetteville, Arkansas, United States

University of California Irvine Medical Center

Irvine, California, United States

University of California, Los Angeles (UCLA) - Institute of Urologic Oncology

Los Angeles, California, United States

Stanford Hospital and Clinics

Stanford, California, United States

Rocky Mountain Cancer Centers

Aurora, Colorado, United States

Georgetown University Medical Center

Washington D.C., District of Columbia, United States

University of Miami

Miami, Florida, United States

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, United States

Loyola University Chicago

Chicago, Illinois, United States

Indiana University Health Melvin & Bren Simon Cancer Center

Indianapolis, Indiana, United States

Beth Israel Deaconess Med Center

Boston, Massachusetts, United States

Lahey Hospital & Medical Center

Burlington, Massachusetts, United States

Nebraska Methodist Hospital

Omaha, Nebraska, United States

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Cancer Center Hackensack UMC

Hackensack, New Jersey, United States

University of New Mexico

Albuquerque, New Mexico, United States

New York Oncology Hematology, P.C.

Albany, New York, United States

North Shore LIJ Center for Advance Medicine

Lake Success, New York, United States

Mem Sloan Kettering Cancer Center

New York, New York, United States

NYU Cancer Institute

New York, New York, United States

Levin Cancer Institute

Charlotte, North Carolina, United States

Cleveland Clinic

Cleveland, Ohio, United States

Northwest Cancer Specialists, P.C.

Tualatin, Oregon, United States

Saint Luke's University Health Network

Bethlehem, Pennsylvania, United States

Penn State Milton S- Hershey Medical Center

Hershey, Pennsylvania, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

University of Pittsburgh, Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Texas Oncology-South Austin

Austin, Texas, United States

Texas Oncology - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, United States

Texas Oncology-El Paso Cancer Treatment Center Grandview

El Paso, Texas, United States

Texas Oncology - Memorial City

Houston, Texas, United States

Texas Oncology - Tyler and Longview

Tyler, Texas, United States

Shenandoah Oncology P.C.

Winchester, Virginia, United States

University of Wisconsin, Carbone Cancer Center

Madison, Wisconsin, United States

Countries

United States

References

Voss MH, Bhatt RS, Vogelzang NJ, Fishman M, Alter RS, Rini BI, Beck JT, Joshi M, Hauke R, Atkins MB, Burgess E, Logan TF, Shaffer D, Parikh R, Moazzam N, Zhang X, Glasser C, Sherman ML, Plimack ER. A phase 2, randomized trial evaluating the combination of dalantercept plus axitinib in patients with advanced clear cell renal cell carcinoma. Cancer. 2019 Jul 15;125(14):2400-2408. doi: 10.1002/cncr.32061. Epub 2019 Apr 5.

Reference Type: DERIVED

PMID: 30951193 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

ACE-041

Identifier Type: OTHER

Identifier Source: secondary_id

A041-04

Identifier Type: -

Identifier Source: org_study_id