A Double-blind, Randomised, Multicentre, Placebo-controlled, Parallel Group, Dose Ranging Study to Assess the Efficacy, Safety, and Pharmacokinetics of an Oral Thrombopoietin Receptor Agonist (SB-497115-GR) Administered at 50, 75, and 100 mg to Cancer Patients receiving Multiple Cycles of Chemotherapy

Conditions: Chemotherapy-Induced Thrombocytopenia (CIT)

Registration Number: EUCTR2004-000368-28-DE

Lead Sponsor: GlaxoSmithKline Group of Companies

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 164

Inclusion Criteria

1.Subjects ?18 years old, who are chemotherapy naïve, with histologically confirmed advanced solid tumor (leukemia and lymphoma are excluded) who are scheduled to received carboplatin/paclitaxel as shown below.
2.Subjects scheduled to receive first-line chemotherapy as carboplatin AUC 5-6 IV over 30 minutes plus paclitaxel 175-225 mg/M2 IV over 3 hours on day 1 every 21 days, with routine pre-medications, i.e., 20 mg dexamethasone [or equivalent] orally 6 and 12 hours pre-paclitaxel, 50 mg IV diphenhydramine [or equivalent] and 300 mg IV cimetidine [or equivalent] 30-60 minutes pre-paclitaxel.
3.ECOG-Zubrod performance status is 0, or 1.
4.Subject has no history of platelet disorders or dysfunction and no history of a bleeding disorder.
5.Subjects have adequate:
•hematologic function (ANC ? 1,500/mm3, hemoglobin ? 9 mg/dL, and platelets ?100,000/mm3 and < 600,000/mm3)
•hepatic function (bilirubin ? 2 mg/dL and alanine aminotransferase ? three times the upper limit of normal),
•renal function (creatinine ? 2.0 mg/dL).
6.Subject has no physical limitation to ingest and retain oral medication.
7.Subject has life expectancy of at least 6 months.
8.Subject is practicing an acceptable method of contraception (documented in chart). Female subjects (or female partners of male subjects) must either be of non-childbearing potential (hysterectomy, bilateral oopherectomy, bilateral tubal ligation or post-menopausal > 1 year), or of childbearing potential and use one of the following acceptable methods of contraception from two weeks prior to administration of study medication, throughout the study, and 28 days after completion or premature discontinuation from the study:
•Complete abstinence from intercourse;
•Intrauterine device (IUD);
•Two forms of barrier contraception (diaphragm plus spermicide, and for males condom plus spermicide);
•Male partner is sterile prior to entry into the study and is the only partner of the female;
•Systemic contraceptives (combined or progesterone only).
9.Subject is able to understand and comply with protocol requirements and instructions and intend to complete the study as planned.
10.Subject has signed and dated written informed consent.
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Subjects with a known history of rapidly progressive disease (marked increase in tumor size [>50%], ascites, or serious symptoms related to underlying cancer in the preceding 4-week period), surgery within the previous 2 weeks, radiotherapy within the previous 4 weeks or any prior chemotherapy.
2.Subjects with known pre-existing cardiac disease, including congestive heart failure, arrhythmias requiring treatment, or myocardial infarction within the preceding 3 months.
3.Subjects with abnormal resting 12-lead ECG at screening that would indicate pre-existing cardiac disease, as noted in exclusion criterion 2.
4.Subjects with known clotting disorder associated with hypercoaguability.
5.Subject has consumed aspirin, aspirin-containing compounds, salicylates, anti-coagulants, quinine or non-steroidal anti-inflammatories (NSAIDs) for > 3 consecutive days within 2 weeks of the study start and would require them at any time during the study.
6.Subject has consumed liquid antacids (e.g. Maalox™, Mylanta™, Amphogel™, milk of magnesia) or chewable antacids (e.g. TUMS™) within 48 hours of the first dose of study medication, and would require them at any time during the study.
7.Subject has consumed rosuvastatin or pravastatin within 1 week of the first dose of study medication and/or will require these medications at any time during the study.
8.Any history of drug-induced thrombocytopenia (e.g., quinine).
9.Anti-coagulant use within 4 weeks prior to study entry.
10.Consumption of any herbal supplements, excluding vitamin or mineral supplements, within 1 week of the study start.
11.Female subjects who are lactating or have a positive beta-hCG at screening.
12.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.