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Advanced Adult Hepatocellular CarcinomaPhase 1/2NCT02024087

Study of Dalantercept and Sorafenib in Patients With Advanced Hepatocellular Carcinoma

A Phase 1/2 study testing Dalantercept plus sorafenib in people with Advanced Adult Hepatocellular Carcinoma, run by Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA at 7 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Adult Hepatocellular Carcinoma
What is being tested?
Dalantercept plus sorafenib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
7 sitesUnited States
Study dates
4 Aug 2014to 22 Sep 2017
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 23Show fewer
  • 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:
  • Curatively resected non melanoma skin cancer.
  • Curatively treated cervical carcinoma in situ.
  • 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

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

United States7 sites

  • Beth Israel Deaconess Medical Center (BIDMC)

    Boston, Massachusetts

  • The University of Chicago Medical Center

    Chicago, Illinois

  • University of Cincinnati Cancer Institute

    Cincinnati, Ohio

  • Hackensack University Medical Center

    Hackensack, New Jersey

  • Memorial Sloan-Kettering Cancer Center

    New York, New York

  • University of Rochester

    Rochester, New York

  • University of Kansas Medical Center (KUMC)

    Westwood, Kansas

Other trials in United States

About this study

Official title: A Phase 1b, Open Label Study of Dalantercept Plus Sorafenib in Patients With Advanced Hepatocellular Carcinoma

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.

Read the detailed description

The initial design of the study was a dose escalating approach in which dalantercept in combination with sorafenib, would be administered at increasing dose levels among 3 cohorts of subjects with HCC in order to determine the Maximum Tolerated Dose (MTD) of the combination. Once the MTD was determined, a forth expansion cohort of subjects would be enrolled at the MTD to assess safety. A total of up to 38 subjects were planned.

The initial cohort (Cohort 1) enrolled 5 subjects at a dalantercept dose level of 0.6 mg/kg once every 3 weeks (Q3W) in combination with sorafenib (400 mg PO once daily). Following an assessment of safety/tolerability by a Safety Review Team, it was recommended to de-escalate the dalantercept dose for Cohort 2 to 0.4 mg/kg Q3W in combination with sorafenib (400 mg PO once daily); 6 subjects were enrolled.

The 0.4 mg/kg dose level was determined to be the MTD, and an additional 10 subjects were enrolled at that dose level in the expansion cohort (Cohort 3).

A formal Statistical Analysis Plan was initially planned for this study. However, due to its early termination, only cursory descriptive statistics were carried out on the available data; no formal SAP was prepared.

Being tested
Dalantercept plus sorafenib

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Dalantercept plus sorafenibDrug

    Also called ACE-041

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

Study groups in NCT02024087
Study groupRoleWhat they receive
Dalantercept 0.6 mg/kg plus sorafenib 400 mgExperimentalCohort 1: Participants received dalantercept 0.6 mg/kg by subcutaneous (SC) injection once every 3 weeks plus sorafenib 400 mg orally (PO) once daily
Receives: Drug: Dalantercept plus sorafenib
Dalantercept 0.4 mg/kg plus sorafenib 400 mgExperimentalCohort 2: Participants will receive dalantercept 0.4 mg/kg SC injection once every 3 weeks plus sorafenib 400 mg PO once daily
Receives: Drug: Dalantercept plus sorafenib
Expansion cohort - dalantercept 0.4 mg/kg plus sorafenib 400 mgExperimentalCohort 3: Participants will receive dalantercept 0.4 mg/kg SC injection once every 3 weeks plus sorafenib 400 mg PO once daily
Receives: Drug: Dalantercept plus sorafenib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: up to approximately 20 weeks

Secondary outcomes (3)

  1. Best Overall Response

    The Best Overall Response (BOR) is the best response recorded from the start of the study treatment until the disease progression/recurrence, scored as one of the following: Complete Response (CR); Partial Response (PR); Stable Disease (SD) or Progressive Disease (PD).

    Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1), a CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. A PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD is defined as At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.

    Measured: up to approximately 20 weeks

  2. Overall Survival (OS)

    The proportion of participants alive from the initiation of treatment through end of study

    Measured: up to approximately 20 weeks

  3. Disease Control Rate (DCR)

    Percentage of patients whose disease improves or remains stable over a certain time period. DCR is the sum of the complete, partial and stable disease rates.

    Measured: up to approximately 20 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Dec 2013 (estimated)
  2. Study start4 Aug 2014
  3. Primary completion5 Jul 2017
  4. Study completion22 Sep 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02024087
Sponsor's protocol ID
A041-05
Other IDs
ACE-041
Status last verified
Feb 2021
First submitted
20 Dec 2013
Last updated
26 Sep 2022
Data monitoring committee
No

Publications

  • 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.

    PubMed 30352941

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Dalantercept plus sorafenib in people with Advanced Adult Hepatocellular Carcinoma, run by Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA at 7 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Adverse Events as a Measure of Safety and Tolerability. (time frame: up to approximately 20 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02024087, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Sep 2022.

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