Study of Dalantercept and Sorafenib in Patients With Advanced Hepatocellular 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:
NCT02024087
First received: December 20, 2013
Last updated: July 23, 2014
Last verified: July 2014
  Purpose

The purpose of this study is to evaluate the safety and tolerability of dalantercept plus sorafenib in patients with advanced hepatocellular carcinoma (HCC) to determine the recommended dose level of dalantercept in combination with sorafenib.


Condition Intervention Phase
Advanced Adult Hepatocellular Carcinoma
Drug: Dalantercept plus sorafenib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1b, Open Label Study of Dalantercept Plus Sorafenib in Patients With Advanced Hepatocellular Carcinoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Number of participants with Adverse Events as a measure of safety and tolerability. [ Time Frame: up to approximately 20 weeks ] [ Designated as safety issue: Yes ]
    Assessed by monitoring AEs using the current active minor version on the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 4.0 (NCI-CTCAE v4 current minor version), physical examinations, vital signs, clinical laboratory test, ECHO, ECG and ADA testing; through final study visit, up to approximately 20 weeks from first dose of dalantercept.


Secondary Outcome Measures:
  • Progression free survival (PFS) [ Time Frame: up to approximately 20 weeks ] [ Designated as safety issue: No ]
    Patents will be assessed for efficacy using RECIST v1.1 evaluating response rate; PFS measured from date of randomization through final study visit (up to approximately 20 weeks from first dose of dalantercept), or until disease progression.

  • Overall survival (OS) [ Time Frame: up to approximately 20 weeks ] [ Designated as safety issue: No ]
  • Time to progression (TTP) [ Time Frame: up to approximately 20 weeks ] [ Designated as safety issue: No ]
    Patents will be assessed using RECIST v1.1 evaluating response rate; TTP measured from date of randomization through final study visit (up to approximately 20 weeks from first dose of dalantercept), or until disease progression.

  • Disease control rate (DCR) [ Time Frame: up to approximately 20 weeks ] [ Designated as safety issue: No ]
    Patents will be assessed using RECIST v1.1 evaluating response rate; DCR from date of randomization through final study visit (up to approximately 20 weeks from first dose of dalantercept), or until disease progression.

  • PD biomarker activities (e.g., ALK1 expression on new or archived tumor biopsy tissue; BMP9/10 levels in serum) [ Time Frame: up to approximately 20 weeks ] [ Designated as safety issue: No ]
    Through final study visit, up to approximately 20 weeks from first dose of dalantercept.


Estimated Enrollment: 20
Study Start Date: June 2014
Estimated Study Completion Date: August 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dalantercept plus sorafenib Drug: Dalantercept plus sorafenib
Subcutaneous (SC) injection of dalantercept once every 3 weeks and oral sorafenib daily.

  Eligibility

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

Inclusion Criteria:

  • Histologically confirmed, locally advanced or metastatic HCC.
  • Child-Pugh Score A (5-6)
  • At least one target lesion that has not been treated with local therapy and is measurable by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
  • Life expectancy of at least 12 weeks.
  • Able to tolerate oral therapy.
  • Appropriate clinical laboratory values within 72 hours prior to study day 1:
  • Females of child bearing potential (defined as sexually mature women who have not undergone hysterectomy or bilateral oophorectomy, or are not naturally postmenopausal ≥ 24 consecutive months) must have negative urine or blood pregnancy test prior to enrollment and use adequate birth control methods (abstinence, oral contraceptives, barrier method with spermicide, or surgical sterilization) during study participation. Males must agree to use a latex condom during any sexual contact with females of child bearing potential while participating in the study and for 12 weeks following the last dose of dalantercept, even if he has undergone a successful vasectomy. Patients must be counseled concerning measures to be used to prevent pregnancy and potential toxicities prior to the first dose of dalantercept.

Exclusion Criteria:

  • Mixed tumor histology
  • Prior systemic therapy for metastatic disease.
  • Adjuvant therapy < 6 months prior to study day 1.
  • Prior treatment with dalantercept or other agent targeting the ALK1 pathway.
  • Prior treatment with sorafenib or other RAF/VEGF targeted therapies.
  • Hepatic radiation, chemoembolization, and radiofrequency ablation < 4 weeks prior to study day 1.
  • Palliative radiation therapy to metastatic sites of disease < 2 weeks prior to study day 1.
  • Interferon therapy < 4 weeks prior to study day 1.
  • Uncontrolled Hepatitis B despite appropriate therapy.
  • Clinically significant pulmonary, endocrine, neurologic, hematologic, gastrointestinal (GI), autoimmune, psychiatric or genitourinary disease unrelated to HCC that in the judgment of the investigator should preclude treatment with dalantercept or sorafenib.
  • Known HIV infection.
  • Clinically significant cardiovascular risk
  • Clinically significant active pulmonary risk
  • Known active gastrointestinal (GI) bleeding.
  • Known bleeding diathesis Known history of hereditary hemorrhagic telangiectasia (HHT).
  • History of another primary cancer, with the exception of:

    1. Curatively resected non melanoma skin cancer.
    2. Curatively treated cervical carcinoma in situ.
    3. Other primary solid tumor with no known active disease in the opinion of the investigator that will not affect patient outcome in the setting of current HCC diagnosis.
  • Major surgery within 4 weeks prior to study day 1 Active infection Anti-coagulation therapy Concomitant treatment with potent CYP3A4 inducers
  • Peripheral edema ≥ grade 2 within 2 weeks prior to study day 1.
  • History of recurrent ascites requiring paracentesis within 4 weeks of study day 1.
  • History of severe (using the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 4.0 [NCI-CTCAE] v4 current minor version ≥ grade 3) allergic or anaphylactic reaction or hypersensitivity to recombinant proteins or excipients
  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: NCT02024087

Contacts
Contact: Clinical Trials Manger clinicaltrials041@acceleronpharma.com

Locations
United States, New York
Acceleron Investigative Site Recruiting
New York, New York, United States
Sponsors and Collaborators
Acceleron Pharma, Inc.
  More Information

No publications provided

Responsible Party: Acceleron Pharma, Inc.
ClinicalTrials.gov Identifier: NCT02024087     History of Changes
Other Study ID Numbers: A041-05, ACE-041
Study First Received: December 20, 2013
Last Updated: July 23, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Carcinoma
Adenocarcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Sorafenib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 30, 2014