Health Condition 1: null- Solid tumors
Conditions
Interventions
Intervention1: Eltrombopag Olamine: 100, 150, 225, 300 mg daily for 5 days before and 5 days after Day 1 chemotherapy in cycle 2 (and subsequent cycles if deemed beneficial for the subject and at the
Sponsors
GlaxoSmithKline Pharmaceuticals Ltd Dr Annie Besant Road Worli Mumbai India
Eligibility
Inclusion criteria
Inclusion criteria: 1. Signed written informed consent. 2. Age of more than or equal to 18 years. 3. Subjects with confirmed solid tumor and scheduled to receive at least two cycles of either gemcitabine monotherapy OR gemcitabine in combination with carboplatin or cisplatin at the same dosages and schedule in the study. Novel anticancer agents (e.g. bevacizumab, erlotinib) may be allowed if considered the standard treatment by the investigator. Note: For patients scheduled to receive any novel anticancer agents (e.g. bevacizumab, erlotinib), consultation and approval from the GSK medical monitor should occur before the subject is enrolled into the study. 4. Life expectancy of at least 3 months, in the opinion of the investigator. 5. ECOG performance status less than or equal to 2. 6. For Phase I: Prechemotherapy platelet count less than or equal to 300 Gi/L in the screening period before the subject start their first planned cycle of treatment with gemcitabine monotherapy OR gemcitabine in combination with carboplatin or cisplatin in the study. 7. For Phase II: Platelet count more than or equal to 25 Gi/L and less than 100 Gi/L at any time in the preceding cycle before entry into the study. 8. Adequate baseline organ function defined by the criteria below: a. Hematologic - Platelets more than or equal to 100 Gi/L on Day 1 of chemotherapy for the first cycle in the study - ANC (absolute neutrophil count) more than or equal to 1.5 × 109/L - Hemoglobin more than or equal to 9 g/dL - Prothrombin time (PT/INR) and activated partial thomboplastin time (aPTT) Within 80 to 120% of the normal range b. Hepatic - Albumin more than or equal to 2.5 g/dL - Serum bilirubin less than or equal to 1.5 x ULN - AST and ALT less than or equal to 3 × ULN without liver metastases or less than or equal to 5 × ULN if documented liver metastases c. Renal - Serum Creatinine less than or equal to 1.2 x ULN Subjects with AST, ALT or bilirubin values outside the range(s) in the table due to Gilberts syndrome or asymptomatic gall stones are not excluded. 9. Women of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to randomization and agree to use effective contraception, during the study and for 4 weeks following the last dose of investigational product. 10. Men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception from 2 weeks prior to randomization until 13 weeks after the last dose of study treatment. 11. Able to swallow and retain orally administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels.
Exclusion criteria
Exclusion criteria: 1. Lactating females. 2. Pre-existing cardiovascular disease (congestive heart failure, New York Heart Association [NYHA] Grade III/IV), or arrhythmia known to increase the risk of thromboembolic events (e.g. atrial fibrillation), unstable angina, or subjects with a QTc >450 msec (QTc >480 msec for subjects with Bundle Branch Block) at study entry, or myocardial infarction within the preceding 6 months. Subjects with a pacemaker or defibrillator are not excluded provided that their cardiac function is within normal ranges. Note: For patients with pre-existing NYHA Grade II cardiovascular disease, the investigator should consult with GSK medical monitor before enrolling the subject into the study. 3. Patients with known factor V leiden, antiphospholipid antibody syndrome, prothrombin gene mutations, ATIII deficiency, protein C deficiency, protein S deficiency OR recent history of arterial or venous thrombosis (stroke, transient ischemic attack, myocardial infarction, deep vein thrombosis or pulmonary embolism) within the preceding 6 months. Note: for patients other with known risk factors for thromboembolism e.g., diabetes, hypercholesterolemia, recent major surgery etc., the investigator should consult with GSK medical monitor before enrolling the patient into the study and all risk factors should be documented in the CRF. 4. Prior surgery within two weeks of study entry or radiotherapy (RT) within four weeks of study entry. Subjects with prior surgery or RT are not permitted into the study unless they have completely recovered from surgery and/or acute RT toxicity except for alopecia. 5. History of prior radiotherapy to more than 20% bone marrow bearing sites. 6. History of platelet agglutination abnormality, platelet disorders or dysfunction or bleeding disorder that prevents reliable measurement of platelet counts. 7. Subjects with a history of CNS metastases or clinical signs or symptoms of brain and/or leptomeningeal metastases confirmed by CT or MRI brain scan unless properly treated. Subjects with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to enrolment will be excluded. - Treated brain metastases are defined a. Having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. Anticonvulsants (stable dose) are allowed. b. Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, LINAC, or equivalent) or a combination as deemed appropriate by the treating physician. 8. Administration of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of investigational product in the study. Concurrent participation in another interventional clinical trial or administration of any investigational drug during the study is also not permitted. 9. A known immediate or delayed hypersensitivity reaction or idiosyncrasy that, in the opinion of the Investigator or GSK Medical Monitor is due to drugs chemically related to eltrombopag or excipients (e.g. mannitol). 10. Subjects with known Hepatitis B, hepatitis C or Human Immunodeficiency Virus (HIV). Subjects with Gilbert's Syndrome are permitted into the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase I: Primary Endpoint Safety and tolerability of eltrombopag as assessed by evaluating adverse events (AE) reporting, and changes from baseline in other safety parameters including clinical laboratory valuesTimepoint: Nine months;Phase II: Effect of eltrombopag compared to placebo on pre-chemotherapy platelet counts will be evaluatedTimepoint: Six months | — |
Secondary
| Measure | Time frame |
|---|---|
| Phase II: Effect of eltrombopag compared to placebo on platelet pharmacodynamicsTimepoint: Six Months;Phase II: Effect of eltrombopag compared to placebo on the incidence and severity of bleeding.Timepoint: Six Months;Phase II: Effect of eltrombopag compared to placebo on the need for platelet transfusion(s).Timepoint: Six Months;Phase II: Relationship between plasma eltrombopag concentrations and pharmacodynamics.Timepoint: Six Months;Phase I: Effect of eltrombopag compared to placebo on chemotherapy dose intensity and dose delay.Timepoint: Nine Months;Phase I: Effect of eltrombopag compared to placebo on platelet pharmacodynamics.Timepoint: Nine Months;Phase I: Relationship between plasma eltrombopag concentrations and pharmacodynamics.Timepoint: Nine Months;Phase II Safety and tolerability of eltrombopag as assessed by evaluating adverse events (AE) reporting, and changes from baseline in other safety parameters including clinical laboratory values.Timepoint: Six Months;Phase II: Effect of eltrombopag compared to placebo on chemotherapy dose intensity and dose delay.Timepoint: Six Months;Phase II: Effect of eltrombopag compared to placebo on HR-QoL.Timepoint: Six Months | — |
Countries
Belgium, India, Italy, Netherlands, Poland, United States of America
Contacts
Public ContactNiranjan Kulkarni
GlaxoSmithKline Pharmaceuticals Ltd.
Outcome results
None listed