E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chemotherapy-Induced Thrombocytopenia (CIT) |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of oral SB-497115-GR at doses of 50, 75, and 100 mg compared with placebo in cycle 2 of carboplatin/paclitaxel chemotherapy, administered to subjects with an advanced solid tumour. |
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E.2.2 | Secondary objectives of the trial |
•Safety and tolerability of oral SB-497115-GR when administered to subjects receiving multiple cycles of carboplatin/paclitaxel chemotherapy. •Pharmacodynamic effect of SB-497115-GR on platelet count and function when administered to subjects receiving multiple cycles of carboplatin/paclitaxel chemotherapy. •Efficacy of SB-497115-GR at doses of 50, 75, and 100 mg in the first cycle and beyond the second cycle of carboplatin/paclitaxel chemotherapy. •Population PK profile of oral SB-497115. •To assess dose intensity of carboplatin/paclitaxel chemotherapy (percent of intended dose delivered) administered to the subjects who are also treated with oral SB-497115-GR. •Incidence and severity of thrombocytopenia-related adverse events (AEs) in subjects receiving multiple cycles of carboplatin/paclitaxel for the treatment of an advanced solid tumor who are also treated with oral SB-497115-GR |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal 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 |
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E.4 | Principal 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the change in platelet count from day 1 in cycle 2 (baseline) to cycle 2 nadir |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 8 |