Study of Dalantercept and Sorafenib in Patients With Advanced Hepatocellular Carcinoma

NCT02024087 | Completed Phase 1 Results

• 2 other identifiers: A041-05ACE-041
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Advanced Adult Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events as a Measure of Safety and Tolerability.

  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.

  up to approximately 20 weeks

Secondary Outcomes (3)

• Best Overall Response

  up to approximately 20 weeks

• Overall Survival (OS)

  up to approximately 20 weeks

• Disease Control Rate (DCR)

  up to approximately 20 weeks

Study Arms (3)

Dalantercept 0.6 mg/kg plus sorafenib 400 mg

EXPERIMENTAL

Cohort 1: Participants received dalantercept 0.6 mg/kg by subcutaneous (SC) injection once every 3 weeks plus sorafenib 400 mg orally (PO) once daily

Drug: Dalantercept plus sorafenib

Dalantercept 0.4 mg/kg plus sorafenib 400 mg

EXPERIMENTAL

Cohort 2: Participants will receive dalantercept 0.4 mg/kg SC injection once every 3 weeks plus sorafenib 400 mg PO once daily

Drug: Dalantercept plus sorafenib

Expansion cohort - dalantercept 0.4 mg/kg plus sorafenib 400 mg

EXPERIMENTAL

Cohort 3: Participants will receive dalantercept 0.4 mg/kg SC injection once every 3 weeks plus sorafenib 400 mg PO once daily

Drug: Dalantercept plus sorafenib

Interventions

Dalantercept plus sorafenib DRUG

Subcutaneous (SC) injection of dalantercept once every 3 weeks and oral sorafenib daily.

Also known as: ACE-041

Dalantercept 0.4 mg/kg plus sorafenib 400 mg; Dalantercept 0.6 mg/kg plus sorafenib 400 mg; Expansion cohort - dalantercept 0.4 mg/kg plus sorafenib 400 mg

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

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

Study Sites (7)

The University of Chicago Medical Center

Chicago, Illinois, United States

Location

University of Kansas Medical Center (KUMC)

Westwood, Kansas, United States

Location

Beth Israel Deaconess Medical Center (BIDMC)

Boston, Massachusetts, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Location

University of Rochester

Rochester, New York, United States

Location

University of Cincinnati Cancer Institute

Cincinnati, Ohio, United States

Location

Related Publications (1)

• Abou-Alfa GK, Miksad RA, Tejani MA, Williamson S, Gutierrez ME, Olowokure OO, Sharma MR, El Dika I, Sherman ML, Pandya SS. A Phase Ib, Open-Label Study of Dalantercept, an Activin Receptor-Like Kinase 1 Ligand Trap, plus Sorafenib in Advanced Hepatocellular Carcinoma. Oncologist. 2019 Feb;24(2):161-e70. doi: 10.1634/theoncologist.2018-0654. Epub 2018 Oct 23.

  PMID: 30352941 DERIVED

MeSH Terms

Interventions

ALK1-Fc fusion protein, human; Sorafenib

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2013
• First Posted: December 31, 2013
• Study Start: August 4, 2014
• Primary Completion: July 5, 2017
• Study Completion: September 22, 2017
• Last Updated: September 26, 2022
• Results First Posted: December 22, 2020

Record last verified: 2021-02

Locations

US (7)