Study of Dalantercept in Patients With Squamous Cell Carcinoma of the Head and Neck

Study Overview
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Brief Summary
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Dalantercept, a soluble form of the activin receptor-like kinase-1 protein, is being studied in patients with squamous cell carcinoma of the head and neck (SCCHN). Dalantercept blocks the development of blood vessels that supply tumors.

Detailed Description
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For cancer cells to grow, they need to have nutrients supplied to them through blood vessels. The study drug, dalantercept, is designed to work by blocking the growth of those blood vessels and preventing cancer cells from growing. The purpose of this study is to find out if dalantercept can cause SCCHN tumors to shrink or stop growing. This study will also evaluate the safety of dalantercept in patients with SCCHN.

Official Title
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An Open-label Phase 2 Study of Dalantercept in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

Conditions
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Squamous Cell Carcinoma of the Head and Neck

Intervention / Treatment
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* Biological: Dalantercept


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Histologically and/or cytologically confirmed, recurrent or metastatic SCCHN of mucosal origin (oral cavity, oropharynx, hypopharynx or larynx) not amenable to further local therapy (surgery, or radiation including re-irradiation); patients with unknown primary SCCHN presumed to be of head and neck mucosal origin are eligible if they meet all other entry criteria. Previously treated with at least one platinum-containing regimen or contraindicated for treatment with a platinum containing therapy. (Note: platinum therapy can occur upfront or after recurrence of disease. Failure of platinum therapy is not required.) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Key Exclusion Criteria: Nasopharyngeal carcinoma, paranasal sinus, salivary gland or primary skin SCCHN. Any other active malignancy for which chemotherapy or other anti-cancer therapy is indicated. Chemotherapy or other anti-cancer therapy or radiation therapy 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. Treatment with another investigational drug 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. Major surgery within 4 weeks prior to study day 1 (patients must have recovered completely from any previous surgery prior to study day 1). Clinically significant cardiovascular risk. Clinically significant active pulmonary risk. Clinically significant active bleeding. Peripheral edema ≥ Grade 1 within 4 weeks prior to study day 1. Pregnant or lactating female patients.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dalantercept<br>dalantercept | Biological: Dalantercept<br>* Subcutaneous dose of dalantercept once every 3 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | ORR is defined as the proportion of patients who met criteria for complete response or partial response. Patients were evaluable for ORR if they had at least one measurable lesion at baseline and at least one disease assessment after baseline. RECIST version 1.1 was used to evaluate efficacy. In addition, patients who developed clinical or radiological progression of disease prior to the scheduled tumor assessment were also considered evaluable for response. The response rate was estimated as the proportion of patients evaluable for response who meet the criteria for complete (CR) and partial response (PR). Per RECIST v1.1 for target lesions and assessed by MRI: complete response (CR), disappearance of all target lesions; partial response (PR), >=30% decrease in the sum of the longest diameter of target lesions; overall response (OR) = CR + PR. | Tumor assessments performed every 6 weeks, up to 30 days after the last dose of dalantercept and/or disease progression, up to approximately 2 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability | Number of participants with at least one adverse event as a measure of safety and tolerability. | Adverse events captured from first dose of dalantercept through 30 days after last dose of dalantercept. | 
| Dalantercept Serum Concentration After Single and Multiple Doses | Pharmacokinetic samples were collected pre- and post- dose on Days: 1, 8, 15, 22, 29, and 43. Reported below is AUC0-t (cycle 1). | Up to 43 days from initiation of treatment. | 
| Dalantercept Serum Concentration After Single and Multiple Doses | Pharmacokinetic samples were collected pre- and post- dose on Days: 1, 8, 15, 22, 29, and 43. Reported below is Cmax (cycle 1). | Up to 43 days from initiation of treatment. | 
| Progression Free Survival (PFS) | PFS is defined as the date of the first dose to the first observation of disease progression (according to RECIST v.1.1) or death due to any cause. Progression is defined using RECIST v1.1 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. | Tumor assessments performed every 6 weeks, up to 30 days after the last dose of dalantercept and/or disease progression, up to approximately 2 years. | 
| Overall Survival (OS) | OS is calculated as the number of months from date of the first dose to the date of death. The last patient treated will be followed for overall survival for 1 year following treatment initiation. | Survival captured until death or at a minimum 1 year from first dose of dalantercept. | 
| Disease Control Rate | Disease control rate will be estimated as the proportion of patients evaluable for response who meet the criteria for complete response, partial response, or stable disease. | Tumor assessments performed every 6 weeks, up to 30 days after the last dose of dalantercept and/or disease progression, up to approximately 2 years. |