- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01284348
To Determine Safe and Effective Dose of Sotatercept for the Treatment of Chemotherapy Induced Anemia in Participants With Advanced Non-small Cell Lung Cancer
An Open-Label Randomized, Phase 2A, Dose-Ranging Study of Sotatercept (ACE-011) for Chemotherapy-Induced Anemia in Subjects With Advanced or Metastatic Solid Tumors Treated With Platinum-Based Chemotherapeutic Regimens
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Men and women >18 years of age
Part 1: Histologically confirmed (cytology or biopsy) solid tumor malignancy, excluding those solid tumors treated with curative intent.
Part 2: Histologically confirmed non-small cell lung cancer
- Documented metastatic disease
- Measurable or non-measurable disease evaluable by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
All of the following laboratory values:
- Hemoglobin ≥6.5 to <11.0 g/dL (≥65 to <110 g/L), due to chemotherapy-induced anemia
- Absolute neutrophil count ≥500/mm^3
- Platelet count ≥75,000/mm^3 (>2 hours since prior platelet transfusion
Adequate renal function
- creatinine clearance ≥40mL/min or ≥50 mL/min if cisplatin is concomitantly administered and
- urine protein / creatinine ratio ≤1.0; or ≤2.0 if bevacizumab (Avastin®) is concomitantly administered
- Hepatic function (bilirubin <1.5 x upper limits of normal (ULN); AST and ALT <3.0 x ULN and ≤5.0 ULN for participants with liver metastases)
Participants must have received:
- at least one cycle and up to 4 cycles (q3w schedule) of platinum-based chemotherapy and be randomized prior to receiving Cycle 5 OR
- at least one cycle and up to 3 months (depending upon regimen) of platinum-based chemotherapy
- >28 days since previous treatment with ESA
- >14 days since last red blood cell transfusions
- Eastern Oncology Cooperative Group (ECOG) Performance status 0-2
- For females of childbearing potential, highly effective method of birth control for at least 28 days before starting study, during participation and at least 112 days following last dose of sotatercept
- Males must use latex condom or non-latex condom not made of (animal) membrane during any sexual contact with female of childbearing potential
- Life expectancy of >3 months
- Willing to adhere to study visit schedule
- Understand and voluntarily sign informed consent
Exclusion Criteria:
Part 2 only, history of prior regimen(s)of platinum-based chemotherapy for metastatic NSCLC and/or history of adjuvant platinum-based chemotherapy with last dose received less than six months prior to the start of current first-line platinum-based chemotherapy for metastatic NSCLC.
- National Cancer Institute Common Terminology for Adverse Events Grade >3 toxicity
- Prior radiation to >20% of whole skeleton
- Prior regimen(s) of platinum based chemotherapy for metastatic disease and/or history of adjuvant platinum-based chemotherapy with the last dose received less than six months prior to the start of current first-line platinum-based chemotherapy for metastatic disease
- Central nervous system metastases
- Clinically significant pulmonary, endocrine, neurologic, gastrointestinal, hepatic, or genitourinary disease unrelated to underlying malignancy
- Classification of 3 or higher heart failure (as classified by New York Heart Association)
- History of thrombosis, deep vein thrombosis, pulmonary emboli, or embolic stroke, if not stable on anticoagulants and/or one of these events occurring in past 6 months
- Diagnosis of a myeloid malignancy or known history of myelodysplasia
- Recent history (within 14 days of Day 1) of IV/oral antibiotics due to post septic episode
- Uncontrolled hypertension. Controlled hypertension is considered clinically stable, and systolic blood pressure (SBP) must be <150 mmHg and diastolic blood pressure (DBP) must be < 00 mmHg.
- Known human immunodeficiency virus (HIV)
- Known active hepatitis B or C antibody
- Iron deficiency
- History of anemia as a result of inherited hemoglobinopathy
- History of anemia due to autoimmune or hereditary hemolysis or gastrointestinal bleeding
- Received treatment with another investigational drug or device within 28 days prior to Day 1, or if the half life of the previous product is known, within 5 times the half life prior to dosing, whichever may be longer.
- Any prior use of sotatercept.
- Pregnant or lactating females or females planning to become pregnant
- History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational product (Refer to the Investigator's Brochure for further information).
- Major surgery within 30 days prior to Day 1 (participants must have completely recovered from any previous surgery prior to Day 1).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Supportive Care
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Sotatercept 15 mg
Participants will receive sotatercept 15 mg by subcutaneous (SC) injection once every 42 days, up to four doses.
|
Sotatercept 15 mg SC injection once every 42 days, up to four doses
Other Names:
|
Experimental: Sotatercept 30 mg
Participants will receive sotatercept 30 mg by SC injection once every 42 days, up to four doses.
|
Sotatercept 30 mg SC injection once every 42 days, up to four doses
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants Who Experienced a Hematopoietic Response
Time Frame: Up to Day 28
|
A hematopoietic response was defined as an increase in a participant's hemoglobin (Hgb) of ≥1.0 g/dL above the study baseline value for 4 consecutive weeks, in the absence of red blood cell transfusion and/or erythropoiesis-stimulating agents.
|
Up to Day 28
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants Who Experienced One or More Adverse Events (AEs)
Time Frame: Up to approximately 6 months
|
An AE is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment.
An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
|
Up to approximately 6 months
|
Time to Progression (TTP)
Time Frame: Up to 6 months
|
TTP was defined as the time from date of randomization to date of diagnosis of progressive disease
|
Up to 6 months
|
Progression Free Survival (PFS)
Time Frame: Up to 12 months
|
PFS was defined as the time from the start of study drug therapy to the first observation of disease progression or death due to any cause, whichever came first
|
Up to 12 months
|
Overall Survival (OS)
Time Frame: Up to 24 months
|
OS was defined as the time between randomization and death
|
Up to 24 months
|
Overall Response Rate (ORR)
Time Frame: Up to 12 months
|
Overall Response was defined as the percentage of participants who achieved an objective confirmed complete (CR) or partial response (PR).
Response was determined according to Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 guidelines.
CR: The disappearance of all known disease and no new sites or disease-related symptoms confirmed at least 4 weeks after initial documentation.
All sites must be assessed, including non-measurable sites, such as effusions, or markers.
PR: At least a 30% decrease in the sum of the longest diameters of target lesions, taking as a reference the baseline sum of the longest diameters confirmed at least 4 weeks after initial documentation and no new non-target lesions and/or unequivocal progression of existing non-target lesions.
PR is also recorded when all measurable disease has completely disappeared, but a non-measurable component (i.e., ascites) is still present but not progressing.
|
Up to 12 months
|
Number of Participants Who Experienced an Improvement in Quality of Life Scores
Time Frame: Up to 6 months
|
Participants were to be assessed on improvement of quality of life using the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale (Version 4.0) and the Lung Cancer Symptom Scale (LCSS).
The FACIT Fatigue score ranges from 0 to 52, with 0 representing the best outcome and 52 representing the worst outcome.
The LCSS is a 9-item patient-rated scale, 6 of which measure major symptoms (loss of appetite, fatigue, cough, dyspnoea, pain, and haemoptysis), and 3 of which are summation items related to total symptomatic distress, activity, and overall quality of life.
Participants responses are measured using the mean score on the 9-item visual analogue scales, with 100-mm lines, with 0 representing the best outcome and 100 representing the worst outcome.
|
Up to 6 months
|
Area Under the Concentration Versus Time Curve From Time 0 to 28 Days (AUC0-28d) of Sotatercept Following a Single Dose
Time Frame: Pre-dose 1 Day 1, 4 hours post-dose Day 1, Day 5, Day 8, Day 11, Day 15, Day 22, Day 28
|
AUC0-28d is a measure of the mean concentration levels of a drug in the plasma from time 0 to 28 days.
|
Pre-dose 1 Day 1, 4 hours post-dose Day 1, Day 5, Day 8, Day 11, Day 15, Day 22, Day 28
|
Area Under the Concentration Versus Time Curve From Time 0 to Infinity (AUC0-inf) of Sotatercept Following a Single Dose
Time Frame: Pre-dose 1 Day 1, 4 hours post-dose Day 1, Day 5, Day 8, Day 11, Day 15, Day 22, Day 29, Day 36, pre-dose 2 Day 43
|
AUC0-inf is the area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time.
|
Pre-dose 1 Day 1, 4 hours post-dose Day 1, Day 5, Day 8, Day 11, Day 15, Day 22, Day 29, Day 36, pre-dose 2 Day 43
|
Maximum Plasma Concentration (Cmax) of Sotatercept Following a Single Dose
Time Frame: Pre-dose 1 Day 1, 4 hours post-dose Day 1, Day 5, Day 8, Day 11, Day 15, Day 22, Day 29, Day 36, pre-dose 2 Day 43
|
Cmax is a measure of the maximum amount of drug in the plasma after a dose is given.
|
Pre-dose 1 Day 1, 4 hours post-dose Day 1, Day 5, Day 8, Day 11, Day 15, Day 22, Day 29, Day 36, pre-dose 2 Day 43
|
Time to Maximum Concetration (Tmax) of Sotatercept Following a Single Dose
Time Frame: Pre-dose 1 Day 1, 4 hours post-dose Day 1, Day 5, Day 8, Day 11, Day 15, Day 22, Day 29, Day 36, pre-dose 2 Day 43
|
Tmax is a measure of the time it takes for a drug to reach maximum concentration in the plasma after the dose is given.
|
Pre-dose 1 Day 1, 4 hours post-dose Day 1, Day 5, Day 8, Day 11, Day 15, Day 22, Day 29, Day 36, pre-dose 2 Day 43
|
Apparent Terminal Half-life (t1/2) of Sotatercept Following a Single Dose
Time Frame: Pre-dose 1 Day 1, 4 hours post-dose Day 1, Day 5, Day 8, Day 11, Day 15, Day 22, Day 29, Day 36, pre-dose 2 Day 43
|
t1/2 is the elimination half-life of study drug: the time it takes for half of the study drug in the blood plasma to dissipate.
|
Pre-dose 1 Day 1, 4 hours post-dose Day 1, Day 5, Day 8, Day 11, Day 15, Day 22, Day 29, Day 36, pre-dose 2 Day 43
|
Apparent Serum Clearance (CL/F) of Sotatercept Following a Single Dose
Time Frame: Pre-dose 1 Day 1, 4 hours post-dose Day 1, Day 5, Day 8, Day 11, Day 15, Day 22, Day 29, Day 36, pre-dose 2 Day 43
|
Apparent serum CL is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
|
Pre-dose 1 Day 1, 4 hours post-dose Day 1, Day 5, Day 8, Day 11, Day 15, Day 22, Day 29, Day 36, pre-dose 2 Day 43
|
Apparent Volume of Distribution (Vz/F) Following a Single Dose of Sotatercept
Time Frame: Pre-dose 1 Day 1, 4 hours post-dose Day 1, Day 5, Day 8, Day 11, Day 15, Day 22, Day 29, Day 36, pre-dose 2 Day 43
|
Vz/F is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
|
Pre-dose 1 Day 1, 4 hours post-dose Day 1, Day 5, Day 8, Day 11, Day 15, Day 22, Day 29, Day 36, pre-dose 2 Day 43
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lung Diseases
- Urogenital Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Uterine Neoplasms
- Genital Neoplasms, Female
- Uterine Cervical Diseases
- Uterine Diseases
- Hematologic Diseases
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Lung Neoplasms
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Genital Diseases
- Genital Diseases, Female
- Uterine Cervical Neoplasms
- Head and Neck Neoplasms
- Carcinoma, Non-Small-Cell Lung
- Carcinoma
- Small Cell Lung Carcinoma
- Anemia
- Carcinoma, Small Cell
Other Study ID Numbers
- 7962-015
- ACE-011-NSCL-001 (Other Identifier: Celgene)
- 2010-022561-10 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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