Chemotherapy-Induced Thrombocytopenia in Subjects With Active Non-Hematological Cancers MedDRA version: 20.0 Level: HLT Classification code 10043555 Term: Thrombocytopenias System Organ Class: 10005329 - Blood and lymphatic system disorders MedDRA version: 20.0 Level: PT Classification code 10043554 Term: Thrombocytopenia System Organ Class: 10005329 - Blood and lymphatic system disorders MedDRA version: 22.1 Level: LLT Classification code 10039884 Term: Secondary thrombocytopenia System Orga
Conditions
Interventions
Product Name: avatrombopag
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Avatrombopag maleate
CAS Number: 677007-74-8
Other descriptive name: AVATROMBOPAG MALEATE
Concentration unit: mg
Sponsors
Sobi, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects who meet all of the following criteria will be eligible to participate in the study: 1. Subject is =18 years of age at the time of informed consent; 2. Subject with a diagnosis with ovarian cancer, lung cancer (small cell or non-small cell), or bladder cancer, requiring systemic chemotherapy; 3. Subject is currently receiving a chemotherapy regimen given in a 21-day or 28-day cycle (other chemotherapy cycle lengths are not allowed), 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; 4. Subject experienced severe thrombocytopenia, defined as 2 platelet counts 12 weeks at Screening and is able to receive at least 2 additional cycles of the current chemotherapy regimen; 8. Females of childbearing potential must agree to use a highly effective method of contraception (eg, total abstinence; an intrauterine device; hormonal contraceptive given orally, by injection, or by implant; double barrier contraception (i.e., condom + diaphragm); or has a vasectomized partner with confirmed azoospermia) throughout the entire study period and for 30 days after investigational product (IP) discontinuation. If currently abstinent, the subject must agree to use an effective method as described above if she becomes sexually active during the study period or for 30 days after IP discontinuation. Male subjects must be either surgically sterile or agree to use a double barrier contraception method (combination of male condom with either cap, diaphragm, or sponge with a spermicide) throughout the entire study period and for 30 days after IP discontinuation; 9. Subject is willing and able to comply with all aspects of the protocol; and 10. Subject must provide written informed consent. Inclusion Criteria for Subjects to Continue Into the Optional Open-Label Extension Period Subjects who meet all of the following criteria will be eligible to continue into the optional Open-Label Extension (OLE) Period: 1. Subject is currently receiving the same chemotherapy agents as were given in the qualifying chemotherapy Cycle X; 2. Subject has an ECOG performance status =2; 3. Females of childbearing potential must agree to use a highly effective method of contraception as previously defined. Male subjects must be either surgically sterile or agree to use a double barrier contraception method (combination of male condom with either cap, diaphragm, or sponge with a spermicide) throughout the entire study period and for 30 days after IP discontinuation; 4. Subject is willing and able to comply with all aspects of the protocol; and 5. Subject must provide consent to continue into the OLE Period. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 80 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number o
Exclusion criteria
Exclusion criteria: 1. Subject has experienced = Grade 2 CIT with a platelet count 175 × 10^9/L at Visit 2 (-1 day); 3. Subject with any history of hematologic malignancies, including leukemia, myeloma, myeloproliferative disease, lymphoma, or myelodysplastic diseases; 4. Subject who received >2 previous lines of chemotherapy (adjuvant/neoadjuvant therapy is considered a previous line; immunotherapy alone is not considered a previous line) or is receiving whole brain radiation during the study treatment period; 5. Subject with an alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >5 × upper limit of normal or total bilirubin =3 × upper limit of normal; 6. Subject has a known medical history of human immunodeficiency virus; 7. Subject has any known clinically significant acute or active bleeding (eg, gastrointestinal or central nervous system) within 7 days of Screening; 8. Subject has a known medical history of genetic prothrombotic syndromes (eg, Factor V Leiden, prothrombin G20210A, or ATIII deficiency); 9. Subject has a recent history (within 3 months of Screening) of significant cardiovascular disease (eg, congestive heart failure exacerbation, arrhythmia known to increase the risk of thromboembolic events [eg, atrial fibrillation], coronary artery stent placement, angioplasty, or coronary artery bypass graft); 10. Subject has a history of arterial or venous thrombosis within 3 months of Screening; 11. Subject has used vitamin K antagonists within 7 days of Screening (use of low molecular weight heparin, Xa inhibitors, or thrombin inhibitors is allowed); 12. Subject has a history of chronic platelet or bleeding disorders or thrombocytopenia due to an etiology other than CIT (eg, chronic liver disease or immune thrombocytopenia purpura); 13. Subject has used moderate or strong inducers of cytochrome P450 (CYP)2C or CYP3A4/5 within 7 days of Screening; 14. Subject has received a thrombopoietin receptor agonist (eg, eltrombopag or romiplostim) or recombinant human thrombopoietin for the treatment of CIT within 3 months of Screening; 15. Subject received a platelet transfusion within 72 hours of randomization; 16. Subject is unable to take oral medication; 17. Subject has any history of a concomitant medical condition that, in the opinion of the Investigator, would compromise the subject’s ability to safely complete the study, such as unstable angina, renal failure requiring hemodialysis, or active infection requiring intravenous antibiotics; 18. Female subjects who are lactating or pregnant at Screening or the Baseline Visit (as documented by a positive serum or urine beta-human chorionic gonadotropin [ß-hCG] test); 19. Subject has hypersensitivity to avatrombopag or any of its excipients; or 20. Subject is currently enrolled in another clinical study with any investigational drug or device within 30 days of Screening; however, participation in observational studies is permitted. Exclusion Criteria for Subjects to Continue Into the Optional Open-Label Extension Period Subjects who meet any of the following criteria will be excluded from continuing into the optional OLE Period: 1. Subject has a platelet count >175 × 10^9/L on the scheduled first day of dosing of avatrombopag prior to chemotherapy; 2. Subject with an alanine aminotransferase (ALT) or aspartate aminotransferase (AST)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of avatrombopag in increasing platelet counts and therefore preventing the need for a platelet transfusion or chemotherapy dose reduction or delay in subjects with CIT.;Secondary Objective: • To evaluate the safety of avatrombopag in subjects with CIT, and • To investigate the effect of avatrombopag on bleeding in subjects with CIT.;Primary end point(s): The primary efficacy endpoint is the proportion of responders who meet all of the following criteria during the period after post-chemotherapy IP treatment in Cycle X+1 through Chemotherapy Day of Cycle X+2: • Not requiring a platelet transfusion; • Not requiring a chemotherapy dose reduction by =15% due to thrombocytopenia; and • Not requiring a chemotherapy delay by =4 days due to thrombocytopenia.;Timepoint(s) of evaluation of this end point: Cycle X+2 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Duration of severe thrombocytopenia defined as a platelet count <50 × 109/L during the period after post-chemotherapy IP treatment in Cycle X+1 through Chemotherapy Day of Cycle X+2; • Change in platelet count from baseline (qualifying chemotherapy cycle [Cycle X]) (nadir) to Cycle X + 1 (nadir); • Proportion of subjects who do not have major or non-major clinically relevant bleeding during the period after post-chemotherapy IP treatment in Cycle X+1 through Chemotherapy Day of Cycle X+2; and • Proportion of subjects who do not receive platelet transfusion during the period after postchemotherapy IP treatment in Cycle X+1 through Chemotherapy Day of Cycle X+2. ;Timepoint(s) of evaluation of this end point: Cycle X + 1 | — |
Countries
Hungary, Poland, Russian Federation, Serbia, Ukraine, United States
Contacts
Public ContactClinical Development
Sobi, Inc.
Outcome results
None listed