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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


Phase 2/Phase 3
18 Years
N/A
Not Enrolling
Both
Anemia, Carcinoma, Non-Small-Cell Lung, Carcinoma, Small-Cell Lung, Bladder Cancer, Cancer of Head and Neck, Uterine Cervical Cancer

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Trial Information

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


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


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).

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Supportive Care

Outcome Measure:

Hematopoietic response

Outcome Description:

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).

Outcome Time Frame:

Up to Day 43

Safety Issue:

No

Principal Investigator

Abderrahmane Laadem, MD

Investigator Role:

Study Director

Investigator Affiliation:

Celgene Corporation

Authority:

United States: Food and Drug Administration

Study ID:

ACE-011-NSCL-001

NCT ID:

NCT01284348

Start Date:

January 2011

Completion Date:

April 2013

Related Keywords:

  • Anemia
  • Carcinoma, Non-Small-Cell Lung
  • Carcinoma, Small-Cell Lung
  • Bladder Cancer
  • Cancer of Head and Neck
  • Uterine Cervical Cancer
  • Chemotherapy induced anemia
  • Non-small cell lung cancer
  • Anemia
  • Urinary Bladder Neoplasms
  • Carcinoma
  • Carcinoma, Non-Small-Cell Lung
  • Uterine Cervical Neoplasms
  • Head and Neck Neoplasms
  • Lung Neoplasms
  • Small Cell Lung Carcinoma
  • Carcinoma, Small Cell

Name

Location

University of Texas Medical Branch Galveston, Texas  77555-1329
Cancer Centers of the Carolinas Greenville, South Carolina  29605
Vanderbilt University Medical Center Nashville, Tennessee  37232-2516
Comprehensive Blood and Cancer Center Bakersfield, California  93309
Loma Linda University Cancer Institute Loma Linda, California  92354
Mary Crowley Medical Research Center Dallas, Texas  75246
University of California Los Angeles Los Angeles, California  90095-6951
Duke University Medical Center Durham, North Carolina  27710
Medical Oncology Care Associates Orange, California  92668
Henry Ford Health System Detroit, Michigan  48202
Dartmouth Hitchcock Medical Center Lebanon, New Hampshire  03756
Lahey Clinic Burlington, Massachusetts  01805
Gabrail Cancer Center Canton, Ohio  44718
Cancer Care Associates Medical Group, Inc. Torrance, California  90505
Allison Cancer Center Midland, Texas  79701
The West Clinic Memphis, Tennessee  38120
Compassionate Cancer Care Medical Group, Inc Fountain Valley, California  92708
Joliet Oncology-Hematology Associates, Ltd. Flossmoor, Illinois  60422
Piedmont Hematology Oncology Associates, PLLC Winston-Salem, North Carolina  
Billings Clinic Billings, Montana  59107-7000
North Valley Hematology Oncology Medical Group Mission Hills, California  91343
Comprehensive Cancer Centers of Nevada (TORI) Las Vegas, Nevada  89109
Ocala Oncology Center PL Ocala, Florida  34474
Willamette Valley Cancer Institute and Research Center Springfield, Oregon  97477
Quincy Medical Group Quincy, Illinois  62301
Purchase Cancer Group Paducah, Kentucky  42002
Iowa Blood & Cancer Care Cedar Rapids, Iowa  52402
Texas Oncology - Bedford Bedford, Texas  76022
Hematology Oncology Associates, PC Stamford, Connecticut  06902
Arizona Oncology Associates, P.C., Phoenix, Arizona  85016
Pacific Cancer Medical Inc. Anaheim, California  92801
Saint Jude Heritage Medical Center Fullerton, California  92835
Central Coast Medical Oncology Group Santa Maria, California  93454
Stockton Hematology Oncology Medical Group, Inc Stockton, California  95204
Saint Mary Regional Cancer Center Grand Junction, Colorado  81501
Minnesota Oncology Associates, PC Minneapolis, Minnesota  55404
Monter Cancer Center, North Shore LIJ Health Systems Lake Success, New York  11042
University of Cincinnati Physician's Inc. Cincinnati, Ohio  45267
Saint Charles Medical Center Bend, Oregon  97701
Oncology & Hematology Associates of Southwest Virginia, Inc Salem, Virginia  24073
Northwestern Medical Specialists, PLLC Tacoma, Washington  98405