Avatrombopag for the Treatment of Chemotherapy-Induced Thrombocytopenia in Adults With Active Non-Hematological Cancers

Study Overview
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Brief Summary
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Phase 3 randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of avatrombopag in subjects with chemotherapy-induced thrombocytopenia receiving chemotherapy for the treatment of ovarian, lung (small cell and non-small cell) and bladder cancer.

Detailed Description
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Subjects will receive placebo controlled test treatment for one cycle of chemotherapy followed by an observational cycle. Subjects will have the option to continue into an open label extension period for all remaining chemotherapy cycles within the current regimen. After the follow-up visit, all subjects will continue to a long-term safety follow-up period.

Official Title
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Randomized, Double-Blind, Placebo-Controlled Study With Open-Label Extension to Evaluate the Efficacy and Safety of Avatrombopag for the Treatment of Chemotherapy-Induced Thrombocytopenia in Subjects With Active Non-Hematological Cancers

Conditions
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Chemotherapy-induced Thrombocytopenia

Intervention / Treatment
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* Drug: Avatrombopag
* Drug: Placebo Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women greater than or equal to 18 years of age; A diagnosis of ovarian, lung (small cell or non-small cell) or bladder cancer requiring systemic chemotherapy Participant receiving a chemotherapy regimen given in a 21 or 28-day cycle, including 1 or more of the following agents or class of agents: Nucleoside analog, including gemcitabine and fluorouracil; Carboplatin or cisplatin; Anthracycline; or Alkylating agent; Participant experienced severe thrombocytopenia, defined as 2 platelet counts <50 x 109/L measured at least 24 hours apart, during the qualifying chemotherapy cycle, of their current chemotherapy regimen ECOG performance status <=2 Exclusion Criteria: Participant has experienced >=Grade 2 CIT other than during the current chemotherapy treatment regimen within 6 months of Screening; Participant has any history of hematologic malignancies, including leukemia, myeloma, myeloproliferative disease, lymphoma, or myelodysplastic diseases; Participant has received >2 previous lines of chemotherapy or is receiving whole brain radiation during the study treatment period; Participant has a known medical history of genetic prothrombotic syndromes Participant has a history of arterial or venous thrombosis within 3 months of screening; Use of vitamin K antagonists; Participant has previously received a thrombopoietin receptor agonist or recombinant human thrombopoietin for the treatment of CIT within 3 months of screening

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Avatrombopag<br>Study is 2:1 randomization ratio (avatrombopag to placebo). Investigational product administered orally once daily for 5 days prior to chemotherapy and 5 days following chemotherapy treatment. | Drug: Avatrombopag<br>* Oral avatrombopag tablet<br>|
| Placebo Comparator: Placebo<br>Study is 2:1 randomization ratio (avatrombopag to placebo). Investigational product administered orally once daily for 5 days prior to chemotherapy and 5 days following chemotherapy treatment. | Drug: Placebo Oral Tablet<br>* Placebo comparator tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Who do Not Require Platelet Transfusion, Dose Reduction in Chemotherapy by 15%, or Chemotherapy Delay by >=4 Days |  | Randomization up to 33 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Severe Thrombocytopenia Defined as a Platelet Count <50 x 10^9/L | The duration of severe thrombocytopenia is defined as the total number of days with a platelet count <50×10^9/L during the period after post-chemotherapy study drug treatment in Cycle X+1 through Chemotherapy Day of Cycle X+2. | Randomization up to 33 days | 
| Change in Platelet Count From Baseline (Nadir) | Comparison of avatrombopag 60 mg vs. placebo, adjusted for the number of chemotherapy agents currently receiving per IWRS (1, ≥2). Cycle X nadir is defined as the lowest platelet count value prior to the first dose of study drug; Cycle X+1 nadir is defined as the lowest platelet count value during the period after post-chemotherapy study drug treatment in Cycle X+1 through Chemotherapy Day in Cycle X+2. | Randomization up to 33 days | 
| Percentage of Subjects Who Did Not Have Major or Non-major Clinically Relevant Bleeding During the Period After Post-chemotherapy Study Drug Treatment in Cycle X+1 Through Chemotherapy Day of Cycle X+2. |  | Randomization up to 33 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Thrombocytopenia, CIT