Study of Dalantercept in Patients With Advanced Renal Cell Carcinoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Acceleron Pharma, Inc.
Sponsor:
Information provided by (Responsible Party):
Acceleron Pharma, Inc.
ClinicalTrials.gov Identifier:
NCT01727336
First received: November 8, 2012
Last updated: July 24, 2014
Last verified: July 2014
  Purpose

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).


Condition Intervention Phase
Advanced Renal Cell Carcinoma
Drug: Dalantercept and axitinib
Drug: Placebo and axitinib
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2 Randomized, Double-Blind Study of Dalantercept and Axitinib Compared to Placebo and Axitinib in Patients With Advanced Renal Cell Carcinoma

Resource links provided by NLM:


Further study details as provided by Acceleron Pharma, Inc.:

Primary Outcome Measures:
  • Part 1: Number of participants with Adverse Events as a measure of safety and tolerability. [ Time Frame: Assessed from time of first dose to approximately 30 days after last dose (approximately 6 months). ] [ Designated as safety issue: Yes ]
  • Part 2: Progression free survival (PFS). [ Time Frame: Progression free survival is defined as the time from the date of the randomization to the first documented disease progression (according to RECIST v1.1) or death due to any cause (approximately 6 months). ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Part 2: Overall survival. [ Time Frame: Patients to be contacted every 3 months for up to 12 months (anticipated) for survival follow-up, as well as tumor assessment scans if progression of disease has not previously been documented. ] [ Designated as safety issue: No ]
  • Part 2: Time to tumor progression. [ Time Frame: Assessed at 30 days after last dose of study drug, or up to approximately 6 months from initiation of treatment. ] [ Designated as safety issue: No ]
  • Part 2: Objective response rate. [ Time Frame: Assessed at 30 days after last dose of study drug, or up to approximately 6 months from initiation of treatment. ] [ Designated as safety issue: No ]
  • Part 2: Duration of response [ Time Frame: Assessed at 30 days after last dose of study drug, or up to approximately 6 months from initiation of treatment. ] [ Designated as safety issue: No ]
  • Part 2: Disease control rate. [ Time Frame: Assessed at 30 days after last dose of study drug, or up to approximately 6 months from initiation of treatment for evaluable patients who meet the criteria for CR, PR or SD a minimum of 6 weeks after initiation of dosing. ] [ Designated as safety issue: No ]
  • Part 2: PD biomarker activities. [ Time Frame: Assessed at 30 days after the last dose of dalantercept ± 10 days. ] [ Designated as safety issue: No ]

Estimated Enrollment: 174
Study Start Date: December 2012
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dalantercept plus axitinib
Subcutaneous (SC) injection of Dalantercept once every 3 weeks and Oral axitinib BID for continuous dosing.
Drug: Dalantercept and axitinib
Other Name: ACE-041, Inlyta
Active Comparator: Placebo plus axitinib
Subcutaneous injection of normal saline once every 3 weeks and oral BID for continuous dosing
Drug: Placebo and axitinib
Other Name: Inlyta

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Key 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: Documented Progression on one or two prior therapies defined as:

    (i) one prior treatment: Either sunitinib or pazopanib inclusive of adjuvant therapy with either agent, if there was documented disease progression during treatment), or (ii) two prior treatments; either sunitinib or pazopanib as listed above and one line of an approved or investigational anticancer immune therapy (e.g., interleukin-2, checkpoint inhibitors or vaccine).

  • A minimum of 2 weeks 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.

Key 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 central nervous system (CNS) metastases or leptomeningeal disease. 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 within 6 weeks prior to study day 1 may be enrolled to part 1 only.
  • 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 5 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 parenteral antibiotic therapy within 1 month prior to study day 1 or systemic antibiotics within 2 weeks of study day 1.
  • Anti-coagulation therapy (e.g., clopidogrel, dabigatran, warfarin, and heparin).
  • Current use of or anticipated inability to avoid potent CTP3A4/5 inhibitors (e.g., grapefruit juice, verapamil, ketoconazole, micronazole, itraconazole, erythromycin, telithromycin, clarithromycin, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir, delavirdine) or CTP3A4/5 inducers (carbamazepine, dexamethasone, felbamate, omeprazole, phenobarbital, phenytoin, amobarbital, nevirapine, primidone, rifabutin, rifampin, St. John's wort) during participation in the study.
  • Peripheral edema 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.
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01727336

Contacts
Contact: Clinical Trials Manager clinicaltrials041@acceleronpharma.com

Locations
United States, District of Columbia
Acceleron Investigative Site Recruiting
Washington, District of Columbia, United States
United States, Georgia
Acceleron Investigative Site Recruiting
Savannah, Georgia, United States
United States, Louisiana
Acceleron Investigative Site Recruiting
Marrero, Louisiana, United States
United States, Massachusetts
Acceleron Investigative Site Recruiting
Boston, Massachusetts, United States
United States, Nebraska
Acceleron Investigative Site Recruiting
Omaha, Nebraska, United States
United States, New Hampshire
Acceleron Investigative Site Recruiting
Lebanon, New Hampshire, United States
United States, New Jersey
Acceleron Investigative Site Recruiting
Camden, New Jersey, United States
Acceleron Investigative Site Recruiting
Hackensack, New Jersey, United States
United States, New York
Acceleron Investigative Site Recruiting
New York, New York, United States
United States, Ohio
Acceleron Investigative Site Recruiting
Cleveland, Ohio, United States
United States, Pennsylvania
Acceleron Investigative Site Recruiting
Philadelphia, Pennsylvania, United States
United States, Texas
Acceleron Investigative Site Recruiting
Dallas, Texas, United States
Sponsors and Collaborators
Acceleron Pharma, Inc.
  More Information

No publications provided

Responsible Party: Acceleron Pharma, Inc.
ClinicalTrials.gov Identifier: NCT01727336     History of Changes
Other Study ID Numbers: A041-04, ACE-041
Study First Received: November 8, 2012
Last Updated: July 24, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Axitinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 26, 2014