To Determine Safe and Effective Dose of Sotatercept for the Treatment of Chemotherapy Induced Anemia in Participants With Advanced Non-small Cell Lung Cancer

NCT ID: NCT01284348

Last Updated: 2024-08-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-25
• Study Completion Date: 2012-09-21

Brief Summary

The purpose of this study was to determine an effective and safe dose of sotatercept (ACE-011) for the treatment of chemotherapy-induced anemia (CIA) in participants with metastatic non-small cell lung cancer (NSCLC) who are being treated with first-line platinum based chemotherapy.

Detailed Description

The ACE-011-NSCL-001 Phase 2a study was an open-label, randomized, dose-ranging study designed to assess the efficacy, safety, tolerability, pharmacokinetic and quality of life of sotatercept for treatment of CIA in participants with advanced or metastatic solid tumors treated with platinum-based chemotherapeutic regimens. Other objectives included the effect of sotatercept treatment on bone metabolism, the evaluation of the expression of Activin A and other proteins/biomarkers (including myostatin and follistatin) and the assessment of renal function biomarkers. The study consisted of a Screening Period, a Treatment Period of approximately 6 months (up to 4 doses of sotatercept at either 15 mg or 30 mg administered subcutaneously every 42 days) and a Post-treatment Follow-up Period or End of Treatment (42 days after the last dose of sotatercept). The study was terminated early due to a slower than expected rate of enrollment as a result of substantial changes in the standard of care for cancer participants with anemia which resulted in challenges to timely accrual and completion of the study. Therefore, 26 participants were randomized into the study and the planned Part 2 of the study consisting of a double-blind, randomized, placebo-controlled Phase 2b/3 study conducted at the optimal dose of sotatercept in up to 750 participants with metastatic NSCLC was not performed. Due to the small sample size and variability of the data, changes were made to modify the study endpoints and revise them to be exploratory only.

Conditions

Anemia; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small-Cell Lung; Bladder Cancer; Cancer of Head and Neck; Uterine Cervical Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: TRIPLE

Study Groups

Sotatercept 15 mg

Participants will receive sotatercept 15 mg by subcutaneous (SC) injection once every 42 days, up to four doses.

Group Type: EXPERIMENTAL

Sotatercept 15 mg

Intervention Type: DRUG

Sotatercept 15 mg SC injection once every 42 days, up to four doses

Sotatercept 30 mg

Participants will receive sotatercept 30 mg by SC injection once every 42 days, up to four doses.

Group Type: EXPERIMENTAL

Sotatercept 30 mg

Intervention Type: DRUG

Sotatercept 30 mg SC injection once every 42 days, up to four doses

Interventions

Sotatercept 15 mg

Sotatercept 15 mg SC injection once every 42 days, up to four doses

Intervention Type: DRUG

Sotatercept 30 mg

Sotatercept 30 mg SC injection once every 42 days, up to four doses

Intervention Type: DRUG

Other Intervention Names

ACE-011; ACE-011

Eligibility Criteria

Inclusion Criteria

1. Men and women >18 years of age

2. 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

3. Documented metastatic disease

4. Measurable or non-measurable disease evaluable by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

5. 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)

6. 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

7. >28 days since previous treatment with ESA

8. >14 days since last red blood cell transfusions

9. Eastern Oncology Cooperative Group (ECOG) Performance status 0-2

10. 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

11. Males must use latex condom or non-latex condom not made of (animal) membrane during any sexual contact with female of childbearing potential

12. Life expectancy of >3 months

13. Willing to adhere to study visit schedule

14. 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.

1. National Cancer Institute Common Terminology for Adverse Events Grade >3 toxicity

2. Prior radiation to >20% of whole skeleton

3. 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

4. Central nervous system metastases

5. Clinically significant pulmonary, endocrine, neurologic, gastrointestinal, hepatic, or genitourinary disease unrelated to underlying malignancy

6. Classification of 3 or higher heart failure (as classified by New York Heart Association)

7. 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

8. Diagnosis of a myeloid malignancy or known history of myelodysplasia

9. Recent history (within 14 days of Day 1) of IV/oral antibiotics due to post septic episode

10. 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.

11. Known human immunodeficiency virus (HIV)

12. Known active hepatitis B or C antibody

13. Iron deficiency

14. History of anemia as a result of inherited hemoglobinopathy

15. History of anemia due to autoimmune or hereditary hemolysis or gastrointestinal bleeding

16. 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.

17. Any prior use of sotatercept.

18. Pregnant or lactating females or females planning to become pregnant

19. 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).

20. Major surgery within 30 days prior to Day 1 (participants must have completely recovered from any previous surgery prior to Day 1).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

Raftopoulos H, Laadem A, Hesketh PJ, Goldschmidt J, Gabrail N, Osborne C, Ali M, Sherman ML, Wang D, Glaspy JA, Puccio-Pick M, Zou J, Crawford J. Sotatercept (ACE-011) for the treatment of chemotherapy-induced anemia in patients with metastatic breast cancer or advanced or metastatic solid tumors treated with platinum-based chemotherapeutic regimens: results from two phase 2 studies. Support Care Cancer. 2016 Apr;24(4):1517-25. doi: 10.1007/s00520-015-2929-9. Epub 2015 Sep 14.

Reference Type: RESULT

PMID: 26370220 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://www.merckclinicaltrials.com

Merck Clinical Trials Information

Other Identifiers

ACE-011-NSCL-001

Identifier Type: OTHER

Identifier Source: secondary_id

2010-022561-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

7962-015

Identifier Type: -

Identifier Source: org_study_id