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AnemiaPhase 2NCT01284348

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

A Phase 2 study testing Sotatercept 15 mg and Sotatercept 30 mg in people with Anemia and Carcinoma, Non-Small-Cell Lung, run by Merck Sharp & Dohme LLC.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Sotatercept 15 mg and Sotatercept 30 mg
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26 participants
Where
No sites listed yet
Study dates
25 Mar 2011to 21 Sep 2012
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Men and women >18 years of age
  • 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
  • Documented metastatic disease
  • Measurable or non-measurable disease evaluable by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
  • All of the following laboratory values:
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  • 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)
  • 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
  • >28 days since previous treatment with ESA
  • >14 days since last red blood cell transfusions
  • Eastern Oncology Cooperative Group (ECOG) Performance status 0-2
  • 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
  • Males must use latex condom or non-latex condom not made of (animal) membrane during any sexual contact with female of childbearing potential
  • Life expectancy of >3 months
  • Willing to adhere to study visit schedule
  • Understand and voluntarily sign informed consent

Who cannot join

  • 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.
  • National Cancer Institute Common Terminology for Adverse Events Grade >3 toxicity
  • Prior radiation to >20% of whole skeleton
  • 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
  • Central nervous system metastases
  • Clinically significant pulmonary, endocrine, neurologic, gastrointestinal, hepatic, or genitourinary disease unrelated to underlying malignancy
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  • Classification of 3 or higher heart failure (as classified by New York Heart Association)
  • 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
  • Diagnosis of a myeloid malignancy or known history of myelodysplasia
  • Recent history (within 14 days of Day 1) of IV/oral antibiotics due to post septic episode
  • 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.
  • Known human immunodeficiency virus (HIV)
  • Known active hepatitis B or C antibody
  • Iron deficiency
  • History of anemia as a result of inherited hemoglobinopathy
  • History of anemia due to autoimmune or hereditary hemolysis or gastrointestinal bleeding
  • 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.
  • Any prior use of sotatercept.
  • Pregnant or lactating females or females planning to become pregnant
  • 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).
  • Major surgery within 30 days prior to Day 1 (participants must have completely recovered from any previous surgery prior to Day 1).

About this study

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

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.

Read the 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.

Being tested
Sotatercept 15 mg, Sotatercept 30 mg
Keywords
Chemotherapy induced anemia, Non-small cell lung cancer
Medical subject headings
Anemia, Carcinoma, Non-Small-Cell Lung, Small Cell Lung Carcinoma, Urinary Bladder Neoplasms, Head and Neck Neoplasms, Uterine Cervical Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Sotatercept 15 mgDrug

    Also called ACE-011

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

  • Sotatercept 30 mgDrug

    Also called ACE-011

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

Study groups in NCT01284348
Study groupRoleWhat they receive
Sotatercept 15 mgExperimentalParticipants will receive sotatercept 15 mg by subcutaneous (SC) injection once every 42 days, up to four doses.
Receives: Drug: Sotatercept 15 mg
Sotatercept 30 mgExperimentalParticipants will receive sotatercept 30 mg by SC injection once every 42 days, up to four doses.
Receives: Drug: Sotatercept 30 mg

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants Who Experienced a Hematopoietic Response

    A hematopoietic response was defined as an increase in a participant's hemoglobin (Hgb) of ≥1.0 g/dL above the study baseline value for 4 consecutive weeks, in the absence of red blood cell transfusion and/or erythropoiesis-stimulating agents.

    Measured: Up to Day 28

Secondary outcomes (13)

  1. Number of Participants Who Experienced One or More Adverse Events (AEs)

    An AE is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.

    Measured: Up to approximately 6 months

  2. Time to Progression (TTP)

    TTP was defined as the time from date of randomization to date of diagnosis of progressive disease

    Measured: Up to 6 months

  3. Progression Free Survival (PFS)

    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

    Measured: Up to 12 months

  4. Overall Survival (OS)

    OS was defined as the time between randomization and death

    Measured: Up to 24 months

  5. Overall Response Rate (ORR)

    Overall Response was defined as the percentage of participants who achieved 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.

    Measured: Up to 12 months

  6. Number of Participants Who Experienced an Improvement in Quality of Life Scores

    Participants were to be assessed on improvement of quality of life using the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale (Version 4.0) and the Lung Cancer Symptom Scale (LCSS). The FACIT Fatigue score ranges from 0 to 52, with 0 representing the best outcome and 52 representing the worst outcome. The LCSS is a 9-item patient-rated scale, 6 of which measure major symptoms (loss of appetite, fatigue, cough, dyspnoea, pain, and haemoptysis), and 3 of which are summation items related to total symptomatic distress, activity, and overall quality of life. Participants responses are measured using the mean score on the 9-item visual analogue scales, with 100-mm lines, with 0 representing the best outcome and 100 representing the worst outcome.

    Measured: Up to 6 months

  7. Area Under the Concentration Versus Time Curve From Time 0 to 28 Days (AUC0-28d) of Sotatercept Following a Single Dose

    AUC0-28d is a measure of the mean concentration levels of a drug in the plasma from time 0 to 28 days.

    Measured: Pre-dose 1 Day 1, 4 hours post-dose Day 1, Day 5, Day 8, Day 11, Day 15, Day 22, Day 28

  8. Area Under the Concentration Versus Time Curve From Time 0 to Infinity (AUC0-inf) of Sotatercept Following a Single Dose

    AUC0-inf is the area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time.

    Measured: Pre-dose 1 Day 1, 4 hours post-dose Day 1, Day 5, Day 8, Day 11, Day 15, Day 22, Day 29, Day 36, pre-dose 2 Day 43

  9. Maximum Plasma Concentration (Cmax) of Sotatercept Following a Single Dose

    Cmax is a measure of the maximum amount of drug in the plasma after a dose is given.

    Measured: Pre-dose 1 Day 1, 4 hours post-dose Day 1, Day 5, Day 8, Day 11, Day 15, Day 22, Day 29, Day 36, pre-dose 2 Day 43

  10. Time to Maximum Concetration (Tmax) of Sotatercept Following a Single Dose

    Tmax is a measure of the time it takes for a drug to reach maximum concentration in the plasma after the dose is given.

    Measured: Pre-dose 1 Day 1, 4 hours post-dose Day 1, Day 5, Day 8, Day 11, Day 15, Day 22, Day 29, Day 36, pre-dose 2 Day 43

  11. Apparent Terminal Half-life (t1/2) of Sotatercept Following a Single Dose

    t1/2 is the elimination half-life of study drug: the time it takes for half of the study drug in the blood plasma to dissipate.

    Measured: Pre-dose 1 Day 1, 4 hours post-dose Day 1, Day 5, Day 8, Day 11, Day 15, Day 22, Day 29, Day 36, pre-dose 2 Day 43

  12. Apparent Serum Clearance (CL/F) of Sotatercept Following a Single Dose

    Apparent serum CL is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.

    Measured: Pre-dose 1 Day 1, 4 hours post-dose Day 1, Day 5, Day 8, Day 11, Day 15, Day 22, Day 29, Day 36, pre-dose 2 Day 43

  13. Apparent Volume of Distribution (Vz/F) Following a Single Dose of Sotatercept

    Vz/F is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.

    Measured: Pre-dose 1 Day 1, 4 hours post-dose Day 1, Day 5, Day 8, Day 11, Day 15, Day 22, Day 29, Day 36, pre-dose 2 Day 43

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2011 (estimated)
  2. Study start25 Mar 2011
  3. Primary completion21 Sep 2012
  4. Study completion21 Sep 2012

Why it stopped: Persistent low enrollment made study continuation no longer feasible

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Supportive care
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
26 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01284348
Sponsor's protocol ID
7962-015
Other IDs
ACE-011-NSCL-001, 2010-022561-10
Status last verified
Jul 2024
First submitted
17 Dec 2010
Last updated
29 Aug 2024
Data monitoring committee
Yes
Individual data sharing
Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

  • 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.

    PubMed 26370220

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Sotatercept 15 mg and Sotatercept 30 mg in people with Anemia and Carcinoma, Non-Small-Cell Lung, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 29 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Oct 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Who Experienced a Hematopoietic Response (time frame: Up to Day 28). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01284348, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Aug 2024.

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