To Determine Safe and Effective Dose of ACE-011 for the Treatment of Chemotherapy Induced Anemia in Patients With Advanced Non-small Cell Lung Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01284348
Recruitment Status : Terminated (Persistent low enrollment made study continuation no longer feasible)
First Posted : January 27, 2011
Last Update Posted : November 17, 2017
Information provided by (Responsible Party):

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

Condition or disease Intervention/treatment Phase
Anemia Carcinoma, Non-Small-Cell Lung Carcinoma, Small-Cell Lung Bladder Cancer Cancer of Head and Neck Uterine Cervical Cancer Drug: Sotatercept 15 mg Drug: Sotatercept 30 mg Phase 2

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 (ACE-011) 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 (ACE-011) in up to 750 subjects 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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Supportive Care
Official Title: 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 Start Date : January 2011
Actual Primary Completion Date : April 2013
Actual Study Completion Date : April 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anemia
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Sotatercept - 15 mg
Sotatercept 15 mg Subcutaneous (SC) Day 1 every 42 days
Drug: Sotatercept 15 mg
Sotatercept 15 mg SC injection every 42 days, up to 4 doses/cycles
Other Name: ACE-011
Experimental: Sotatercept 30 mg
Sotatercept 30 mg SC Day 1 every 42 days
Drug: Sotatercept 30 mg
Sotatercept 30 mg subcutaneous injection Day 1 every 42 days, up to 4 doses/cycles
Other Name: ACE-011

Primary Outcome Measures :
  1. Hematopoietic response [ Time Frame: Up to Day 43 ]
    Hematopoietic response in ~70% of subjects (defined as an increase in hemoglobin of > 1.0g/dL, above the study baseline for 4 consecutive weeks, in absence of red blood cell transfusion and/or Erythropoiesis-stimulating agents (ESAs).

Secondary Outcome Measures :
  1. Adverse Events [ Time Frame: Up to 6 months ]
    Number of participants with adverse events

  2. Disease progression [ Time Frame: Up to 6 months ]
    Time to progression (TTP) TTP was the time between randomization and disease progression

  3. Progression free survival (PFS) [ Time Frame: 6 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

  4. Overall survival (OS) [ Time Frame: Up to 24 months ]
    OS was defined as the time between randomization and death

  5. Overall response rate (ORR) [ Time Frame: Up to Day 15 ]

    Overall Response is defined as the percent of participants who achieve 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.

  6. Serum concentration of ACE-011 [ Time Frame: Up to 5 months ]
    Serum concentration of ACE-011; AUC-t: area under the plasma concentration time-curve from Time 0 to the time of the last quantifiable concentration (Ct) of Sotatercept

  7. Maximum ACE-011 concentration [ Time Frame: Up to 5 months ]
    Cmax; maximum observed concentration after the first dose of Sotatercept

  8. Quality of Life [ Time Frame: Up to 6 months ]
    Quality of Life (QoL) assessment: Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale (Version 4) and Lung Cancer Symptom Scale (LCSS)

  9. Time to reach the maximum ACE-011 concentration [ Time Frame: Up to 5 months ]
    Time to first maximum observed plasma concentration of ACE-011 in days

  10. Area under the concentration versus time curve [ Time Frame: Up to 5 months ]
    Area under the concentration-time curve AUC-t: area under the plasma concentration time-curve from Time 0 to the time of the last quantifiable concentration (Ct) after the first dose

  11. Terminal Elimination Half-life [ Time Frame: Up to 5 months ]
    Terminal elimination half-life (t1/2) in plasma, was calculated as t1/2,z

  12. Apparent Serum Clearance (CL/F) [ Time Frame: Up to 5 months ]
    Apparent total plasma clearance of ACE-011 - milliliters/minute

  13. Apparent Volume of distribution (Vz) [ Time Frame: Up to 5 months ]
    Apparent Volume of distribution of ACE-011 after first dose - liters

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 (> 72 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 subjects with liver metastases)
  6. Subjects 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 ACE-011
  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 < 100 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 (ACE-011).
  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 (subjects must have completely recovered from any previous surgery prior to Day 1).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01284348

  Show 41 Study Locations
Sponsors and Collaborators
Study Director: Abderrahmane Laadem, MD Celgene

Responsible Party: Celgene Identifier: NCT01284348     History of Changes
Other Study ID Numbers: ACE-011-NSCL-001
First Posted: January 27, 2011    Key Record Dates
Last Update Posted: November 17, 2017
Last Verified: November 2017

Keywords provided by Celgene:
Chemotherapy induced anemia
Non-small cell lung cancer

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Uterine Cervical Neoplasms
Urinary Bladder Neoplasms
Head and Neck Neoplasms
Carcinoma, Small Cell
Small Cell Lung Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Hematologic Diseases
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Urologic Neoplasms
Urinary Bladder Diseases
Urologic Diseases