Neoplasms

All Conditions

Digestive System Diseases

Carcinoma

Carcinoma, Hepatocellular

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Antineoplastic Agents

All Drugs and Chemicals

Sorafenib

Protein Kinase Inhibitors

Enzyme Inhibitors

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

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

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

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

Dalantercept plus sorafenib

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.

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.

Study of Dalantercept and Sorafenib in Patients With Advanced Hepatocellular Carcinoma

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

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.

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.

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

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.

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

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

Dalantercept 0.4 mg/kg Plus Sorafenib

Dalantercept 0.6 mg/kg Plus Sorafenib

Cohort 1: participants were administered dalantercept 0.6 mg/kg by subcutaneous injection once every 3 weeks plus sorafenib 400 mg orally once daily

Dalantercept 0.6 mg/kg Plus Sorafenib 400 mg

Cohort 2: participants were administered dalantercept 0.4 mg/kg by subcutaneous injection once every 3 weeks plus sorafenib 400 mg orally once daily

Dalantercept 0.4 mg/kg Plus Sorafenib 400 mg

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

United States

Region of Enrollment

Eastern Cooperative Oncology Group (ECOG) status is used by healthcare professionals to assess how a patient's disease is progressing, assess how the disease affects the daily living abilities of the patient, and determine appropriate treatment and prognosis.

A score of 0 indicates that a participant is fully active, able to carry on all pre-disease performance without restriction.

A score of 1 indicate that a participant is restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work

ECOG status

Senior Vice President, Global Clinical Development

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

Best Overall Response

Dalantercept plus sorafenib: Subcutaneous (SC) injection of dalantercept once every 3 weeks

Overall Survival (OS)

Disease Control Rate (DCR)

Cohort 1: Participants were administered dalantercept 0.6 mg/kg by subcutaneous injection once every 3 weeks and sorafenib 400 mg orally once daily

Cohort 2: Participants were administered dalantercept 0.4 mg/kg by subcutaneous injection once every 3 weeks and sorafenib 400 mg orally once daily

Spots Global Cancer Trial Database for dalantercept plus sorafenib