Clinical trial NCT00931606: Study of Sotatercept for the Treatment of Chemotherapy Induced Anemia in Patients With Metastatic Breast Cancer (MK-7962-012)
Official title: A Phase 2, Double-blind, Randomized, Placebo-Controlled Study of ACE-011 for the Treatment of Chemotherapy Induced Anemia in Patients With Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Chemotherapy Induced Anemia
Keywords: anemia
metastatic
breast
cancer
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2009-07-02
Enrollment: 30
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the percentage of participants in each sotatercept dose regimen who achieve a hematopoietic response during the treatment period including up to 2 months after the last dose of sotatercept treatment of chemotherapy-induced anemia (CIA) in participants with metastatic breast cancer. Hematopoietic response was defined as an increase in hemoglobin concentration of ≥ 1 g/dL relative to baseline for 28 consecutive days during the treatment period including up to 2 months after the last dose of sotatercept in the absence of red blood cell (RBC) transfusion or treatment with an erythropoiesis-stimulating agent (ESA).


Eligibility criteria: Inclusion Criteria:

* Has a histologically confirmed diagnosis of breast cancer documented by cytology or biopsy.
* Has evidence of metastatic breast cancer with a minimum of one lesion per Response Evaluation Criteria in Solid Tumors v 1.1 (RECIST v 1.1) criteria.
* Is receiving a chemotherapy regimen including one of the following: anthracycline, taxane, gemcitabine, vinorelbine or capecitabine.
* Has planned treatment with the same chemotherapy regimen for a minimum of 9 weeks after Day 1 of study intervention administration.
* ≥ 30 days elapsed (from Day 1) since previous treatment with an erythropoiesis stimulating agent (ESA) (including treatment with intravenous (IV) iron) for chemotherapy induced anemia.
* ≥ 7 days elapsed (from Day 1) since the last red blood cell (RBC) transfusion and receipt of ≤ 2 units of blood in the past 30 days.
* Life expectancy of ≥ 6 months.

Exclusion Criteria:

* Has had prior radiation therapy to \> 20% of the whole skeleton.
* Has had \> 5 prior chemotherapy treatment regimens for metastatic breast cancer.
* Has a history of autoimmune or hereditary hemolysis or gastrointestinal bleeding.
* Has clinically significant pulmonary, endocrine, neurologic, gastrointestinal, hepatic or genitourinary disease unrelated to underlying hematologic disorder.
* Has heart failure as classified by the New York Heart Association (NYHA) classification of 3 or higher.
* Has a recent history of thrombosis, deep vein thrombosis (DVT), pulmonary emboli, or embolic stroke, occurring within the last 6 months.
* Has untreated central nervous system (CNS) metastases or CNS metastases treated with whole brain radiotherapy \< 6 months prior to Day 1.
* Has a diagnosis of a myeloid malignancy or known history of myelodysplasia.
* Has a history of second malignancy within 5 years (except excised and cured basal cell carcinoma, squamous cell carcinoma of the skin or cervical carcinoma in situ).
* Has had administration of IV antibiotics or febrile (temperature elevation \> 38 ° C) within 14 days of Day 1.
* Has uncontrolled hypertension.
* Has known history of hepatitis B surface antigen (HBsAg and HB core antibody (Ab)), human immunodeficiency virus (HIV) antibody or active hepatitis C.
* Has clinically significant iron (transferrin saturation \< 20%), vitamin B12, or folate deficiency.
* Has a history of anemia as a result of inherited hemoglobinopathy such as sickle cell anemia or thalassemia.
* Has a history of autoimmune or hereditary hemolysis; active gastrointestinal bleeding (within the last 6 months as compared to Day 1).
* Has received treatment with another investigational drug or device within 1 month prior to Day 1.
* Is pregnant or lactating.
* Has a history of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational product.
* Has had major surgery within 30 days prior to Day 1 (patients must have completely recovered from any previous surgery prior to Day 1).

Primary outcomes:
measure: Percentage of Participants Who Achieved a Hematopoietic Response
timeFrame: Baseline and Up to ~145 Days
Secondary outcomes:
measure: Number of Participants Who Experienced an Adverse Event (AE)
timeFrame: Up to ~175 Days
measure: Number of Participants Who Discontinued Study Intervention Due to an Adverse Event
timeFrame: Up to ~85 Days
measure: Percentage of Participants Achieving an Increase From Baseline Hemoglobin of ≥ 2 g/dL
timeFrame: Baseline and Up to ~145 Days
measure: Percentage of Participants Achieving an Increase From Baseline Hemoglobin ≥ 11 g/dL
timeFrame: Baseline and Up to ~145 Days
measure: Percentage of Participants Achieving an Increase From Baseline Hemoglobin of ≥2 g/dL and/or Hemoglobin ≥ 11 g/dL
timeFrame: Baseline and Up to ~145 Days
measure: Duration of Hematopoietic Response for Hemoglobin ≥ 1 g/dL
timeFrame: Baseline and Up to ~145 Days
measure: Duration of Hematopoietic Response for Hemoglobin ≥ 2 g/dL
timeFrame: Baseline and Up to ~145 Days
measure: Duration of Hematopoietic Response for Hemoglobin ≥ 11 g/dL
timeFrame: Baseline and Up to ~145 Days
measure: Duration of Hematopoietic Response for Hemoglobin Increases ≥ 1 g/dL and/or Hemoglobin Concentration ≥ 11 g/dL
timeFrame: Baseline and Up to ~145 Days
measure: Duration of Hematopoietic Response for Hemoglobin Increases ≥ 2 g/dL, and/or Hemoglobin Concentration ≥ 11 g/dL
timeFrame: Baseline and Up to ~145 Days
measure: Time to Achieve Hematopoietic Response of Hemoglobin ≥ 1 g/dL Increase From Baseline
timeFrame: Baseline and Up to ~145 Days
measure: Time to Achieve Hematopoietic Response of Hemoglobin ≥ 2 g/dL Increase From Baseline
timeFrame: Baseline and Up to ~145 Days
measure: Time to Achieve Hematopoietic Response of Hemoglobin ≥ 11 g/dL From Baseline
timeFrame: Baseline and Up to ~145 Days
measure: Time to Achieve Hematopoietic Response of First Hemoglobin Increase ≥ 1 g/dL and/or Hemoglobin ≥ 11 g/dL
timeFrame: Baseline and Up to ~145 Days
measure: Time to Achieve Hematopoietic Response of First Hemoglobin Increase ≥ 2 g/dL and/or Hemoglobin ≥ 11 g/dL
timeFrame: Baseline and Up to ~145 Days
measure: Percentage of Participants Who Received RBC Transfusion or Treatment With an ESA
timeFrame: Up to Day 141
measure: Objective Response Rate (ORR) for Target Lesions at Day 64 Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v 1.1).
timeFrame: Baseline and Day 64
measure: Objective Tumor Response Rate for Non-target Lesions at Day 64 Using RECIST v 1.1.
timeFrame: Day 64
measure: Objective Tumor Response Rate for Target Lesions on Day 113 Using RECIST v 1.1.
timeFrame: Day 113
measure: Objective Tumor Response Rate for Non-target Lesions on Day 113 Using RECIST v 1.1.
timeFrame: Day 113
measure: Progression-free Survival (PFS)
timeFrame: From start of chemotherapy (which could have occurred prior to study start) up to Study Day 281
Other outcomes:
Locations:
city: Sedona
country: United States
facility: Investigative Site
state: Arizona
city: Hot Springs
country: United States
facility: Investigative Site
state: Arkansas
city: Beverly Hills
country: United States
facility: Investigative Site
state: California
city: Corona
country: United States
facility: Investigative Site
state: California
city: Fountain Valley
country: United States
facility: Investigative Site
state: California
city: Montebello
country: United States
facility: Investigative Site
state: California
city: Riverside
country: United States
facility: Investigative Site
state: California
city: Denver
country: United States
facility: Investigative Site
state: Colorado
city: Boynton Beach
country: United States
facility: Investigative Site
state: Florida
city: Hinsdale
country: United States
facility: Investigative Site
state: Illinois
city: Evansville
country: United States
facility: Investigative Site
state: Indiana
city: Wichita
country: United States
facility: Investigative Site
state: Kansas
city: Baltimore
country: United States
facility: Investigative Site
state: Maryland
city: Grand Rapids
country: United States
facility: Investigative Site
state: Michigan
city: Tupelo
country: United States
facility: Investigative Site
state: Mississippi
city: Kansas City
country: United States
facility: Investigative Site
state: Missouri
city: Nyack
country: United States
facility: Investigative Site
state: New York
city: Goldsboro
country: United States
facility: Investigative Site
state: North Carolina
city: High Point
country: United States
facility: Investigative Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Investigative Site
state: North Carolina
city: Bismarck
country: United States
facility: Investigative Site
state: North Dakota
city: Middletown
country: United States
facility: Investigative Site
state: Ohio
city: Philadelphia
country: United States
facility: Investigative Site
state: Pennsylvania
city: Charleston
country: United States
facility: Investigative Site
state: South Carolina
city: Austin
country: United States
facility: Investigative Site
state: Texas
city: Dallas
country: United States
facility: Investigative Site
state: Texas
city: Tyler
country: United States
facility: Investigative Site
state: Texas
city: Lacey
country: United States
facility: Investigative Site
state: Washington
city: Krasnodar
country: Russian Federation
facility: Investigative Site
city: Moscow (1)
country: Russian Federation
facility: Investigative Site
city: Moscow (2)
country: Russian Federation
facility: Investigative Site
city: Nizhny Novgorod
country: Russian Federation
facility: Investigative Site
city: Nizhny Novograd (2)
country: Russian Federation
facility: Investigative Site
city: Pyatigorsk
country: Russian Federation
facility: Investigative Site
city: St. Petersburg (1)
country: Russian Federation
facility: Investigative Site
city: St. Petersburg (2)
country: Russian Federation
facility: Investigative Site
city: St. Petersburg (3)
country: Russian Federation
facility: Investigative Site
city: St. Petersburg (4)
country: Russian Federation
facility: Investigative Site
city: Stavropol
country: Russian Federation
facility: Investigative Site
Study officials:
affiliation: Merck Sharp and Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.