Study of ACE-011 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

This study has been terminated.
(Persistent low enrollment made study continuation no longer feasible)
Information provided by (Responsible Party):
Celgene Corporation Identifier:
First received: December 17, 2010
Last updated: August 27, 2014
Last verified: August 2014
The purpose of this study is to determine an effective and safe dose of ACE-011 for the treatment of chemotherapy induced anemia (CIA) in patients with metastatic non-small cell lung cancer who are being treated with first-line platinum based chemotherapy.

Condition Intervention Phase
Carcinoma, Non-Small-Cell Lung
Carcinoma, Small-Cell Lung
Bladder Cancer
Cancer of Head and Neck
Uterine Cervical Cancer
Drug: ACE-011 - 15 mg
Drug: ACE-011 - 30 mg
Drug: ACE-011 - 45 mg
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Supportive Care
Official Title: An Open-Label Randomized, Phase 2A, Dose-ranging Study (Part 1) of Sotatercept (ACE-011) for Chemotherapy-Induced Anemia in Subjects With Advanced or Metastatic Solid Tumors Treated With Platinum-Based Chemotherapeutic Regimens Followed by a Phase 2B/3, Double-blind, Randomized, Placebo-controlled Study (Part 2) of Sotatercept (Ace-011) for Chemotherapy-Induced Anemia in Subjects With Metastatic Non-small Cell Lung Cancer Treated With First-line Platinum-based Chemotherapeutic Regimens

Resource links provided by NLM:

Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • Hematopoietic response [ Time Frame: Up to Day 43 ] [ Designated as safety issue: No ]
    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).

  • Rate of transfusion following treatment [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Adverse Events [ Time Frame: Up to 6 months ] [ Designated as safety issue: Yes ]
    Number of participants with adverse events

  • Disease progression [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
    Time to progression (TTP)

  • Progression free survival (PFS) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Progression free survival (PFS)

  • Progression free survival (PFS) [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
    Progression free survival (PFS)

  • Overall survival (OS) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Overall survival (OS)

  • Overall survival (OS) [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
    Overall survival (OS)

  • Overall response rate (ORR) [ Time Frame: Up to Day 15 ] [ Designated as safety issue: No ]
    Overall response rate (ORR)

  • Serum concentration of ACE-011 [ Time Frame: Up to 5 months ] [ Designated as safety issue: No ]
    Serum concentration of ACE-011

  • Pharmacokinetics (PK) [ Time Frame: Up to 5 months ] [ Designated as safety issue: No ]
    Maximum ACE-011 concentration in serum-nanograms/milliliter

  • Quality of Life [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
    Quality of Life (QoL) assessment: Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale (Version 4) and Lung Cancer Symptom Scale (LCSS)

  • Pharmacokinetics [ Time Frame: Up to 5 months ] [ Designated as safety issue: No ]
    Time to reach the maximum ACE-011 concentration - days

  • Pharmacokinetics [ Time Frame: Up to 5 months ] [ Designated as safety issue: No ]
    Area under the concentration-time curve in serum - nanograms/milliliter

  • Pharmacokinetics [ Time Frame: Up to 5 months ] [ Designated as safety issue: No ]
    Half-life of ACE-011 in serum - days

  • Pharmacokinetics [ Time Frame: Up to 5 months ] [ Designated as safety issue: No ]
    Clearance of ACE-011 - milliliters/minute

  • Pharmacokinetics [ Time Frame: Up to 5 months ] [ Designated as safety issue: No ]
    Volume of distribution of ACE-011 - liters

Enrollment: 25
Study Start Date: January 2011
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ACE-011 - 15 mg
ACE-011 - 15 mg
Drug: ACE-011 - 15 mg
15 mg subcutaneous injection every 42 days, up to 4 doses/cycles
Other Names:
  • Sotatercept
  • ACE-011
Experimental: ACE-011 - 30 mg
ACE-011 - 30 mg
Drug: ACE-011 - 30 mg
30 mg subcutaneous injection every 42 days, up to 4 doses/cycles
Other Names:
  • Sotatercept
  • ACE-011
Experimental: ACE-011 - 45 mg
ACE-011 - 45 mg
Drug: ACE-011 - 45 mg
45 mg subcutaneous injection every 42 days, up to 4 doses/cycles
Other Name: Sotatercept

Detailed Description:

Part 1: Metastatic non-small and small cell lung cancer, metastatic bladder, head and neck, and cervical cancer: Modified to expand eligible tumor types to include advanced or metastatic solid tumors treated with first-line platinum-based chemotherapy, excluding those solid tumors treated with curative intent, in Part 1 of the study.

Part 2 metastatic non small cell lung cancer; Modified to confirm only metastatic NSCLC subjects are eligible for Part 2 of the study


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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)
  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/mm3
    • Platelet count ≥ 75,000/mm3 (> 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 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).
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01284348

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Sponsors and Collaborators
Celgene Corporation
Study Director: Abderrahmane Laadem, MD Celgene Corporation
  More Information

No publications provided

Responsible Party: Celgene Corporation Identifier: NCT01284348     History of Changes
Other Study ID Numbers: ACE-011-NSCL-001 
Study First Received: December 17, 2010
Last Updated: August 27, 2014
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Carcinoma, Small Cell
Head and Neck Neoplasms
Small Cell Lung Carcinoma
Uterine Cervical Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Genital Diseases, Female
Genital Neoplasms, Female
Hematologic Diseases
Lung Diseases
Lung Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Urogenital Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Uterine Neoplasms processed this record on February 08, 2016