Last updated: 11/04/2018 03:33:27
SB-497115 (Oral Thrombopoietin Receptor Agonist) Versus Placebo In Adult Cancer Patients Receiving Chemotherapy
Clinicaltrials.gov ID
EudraCT ID
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: A Double-Blind, Randomized, Multicenter, Placebo-Controlled, Parallel Group, Dose Ranging Study to Assess the Efficacy, Safety, and Pharmacokinetics of an Oral Thrombopoietin Receptor Agonist(SB497115-GR) Administered at 50, 75, and 100 mg to Cancer Patients Receiving Multiple Cycles of Chemotherapy
Trial description: SB497115 is an oral agent which activates the thrombopoietin receptor and increases platelet counts in healthy volunteers. This study is examining several different doses of SB497115 versus placebo as treatment for patients with advanced solid tumors scheduled to receive chemotherapy with carboplatin and paclitaxel every 21 days. Patients will receive SB497115 on days 2-11 of each 21 day cycle for at least 2 cycles of chemotherapy and for a maximum of 8 cycles of chemotherapy.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation:
Randomized
Primary outcomes:
Change in baseline platelet count from the first day of the second cycle of chemotherapy to the lowest count observed (nadir) during the cycle(21 days)
Timeframe: throughout entire study
Secondary outcomes:
Safety and tolerability, pharmacodynamics, changes in platelet count during cycle 1(21 days) and beyond cycle 2(21 days), population PK, and deliver intended doses of chemotherapy without thrombocytopenia related AEs
Timeframe: Throughout entire study
Safety and tolerability as indicated by physical exam, 12-lead ECGs, ophthalmologic examinations, clinical laboratory tests, clinical monitoring/observation, and AE reporting
Timeframe: throughout study
Pharmacodynamic parameters including platelet count, grade of thrombocytopenia,serum thrombopoietin, and platelet aggregation/activation during the first and second cycles of carboplatin/paclitaxel
Timeframe: During first and second cycles of carboplatin/paclitaxel
Change in platelet count from day 1 (baseline) to nadir during the first cycle and beyond the second cycle of carboplatin/paclitaxel
Timeframe: throughout study
Population PK of SB-497115, including clearance (CL/F), absorption rate constant(ka), and volume of distribution (V/F) with assessment of demographic covariates influencing SB-497115 PK
Timeframe: throughout study
The relationship between PK of SB-497115 andrelevant safety and efficacy endpoints will be explored
Timeframe: throughout study
Dose intensity (percent of intended dose) of carboplatin/paclitaxel
Timeframe: N/A
Carboplatin/paclitaxel-associated thrombocytopenia-related AEs, as defined by NCI
Timeframe: N/A
Common Terminology Criteria for Adverse Events, CTCAE v3.0, to include the number of platelet transfusions, bleeding events (hematoma), hemorrhage/bleeding,petechiae/purpura), clinical laboratory tests, and clinical observations
Timeframe: throughout study
Interventions:
Enrollment:
183
Primary completion date:
Not applicable
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Hayes S, Mudd PN, Ouellet D, Johnson BM, Williams D, Gibiansky E. Population PK/PD Modeling of Eltrombopag in Subjects with Advanced Solid Tumors with Chemotherapy-Induced Thrombocytopenia. Cancer Chemother Pharmacol. 2013;71(6):1507-1520.
Kellum A, Jagiello-Gruszfeld A, Bondarenko IN, Patwardhan R, Messam C, Mostafa Kamel Y. A randomized, double-blind, placebo-controlled, dose ranging study to assess the efficacy and safety of eltrombopag in patients receiving carboplatin/paclitaxel for advanced solid tumors. [Curr Med Res Opin]. 2010;26(10):2339-46.
Medical condition
Thrombocytopaenia
Product
eltrombopag
Collaborators
Not applicable
Study date(s)
February 2005 to February 2007
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
- Subjects ≥18 years old, who are chemotherapy naïve, with histologically or cytologically confirmed advanced solid tumor (leukemia and lymphoma are
- excluded) who are scheduled to received carboplatin/paclitaxel as shown below. For the purpose of this study, advanced tumors are defined as tumors that are being treated with palliative intent (i.e., not being treated with curative intent).
- Any clinically relevant abnormality, other than cancer, identified on the screening examination, or any other medical condition or circumstance, which in the opinion of the Investigator, makes the subject unsuitable for participation in the study and/or would make the patient's data difficult to interpret.
- 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.
Inclusion and exclusion criteria
Inclusion criteria:
- Subjects ≥18 years old, who are chemotherapy naïve, with histologically or cytologically confirmed advanced solid tumor (leukemia and lymphoma are excluded) who are scheduled to received carboplatin/paclitaxel as shown below. For the purpose of this study, advanced tumors are defined as tumors that are being treated with palliative intent (i.e., not being treated with curative intent).
- 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.
- ECOG-Zubrod performance status is 0, or 1.
- Subject has no history of platelet disorders or dysfunction and no history of a bleeding disorder.
- Subjects have adequate: hematologic function (ANC ≥ 1,500/mm3, hemoglobin ≥ 9 g/dL, and platelet count ≥100,000/mm3 and < upper limit of normal range (eg, 400,000 to 450,000/mm3), hepatic function (bilirubin ≤ 2 mg/dL and alanine aminotransferase ≤ three times the upper limit of normal), renal function (creatinine ≤ 2.0 mg/dL).
- Subject has no physical limitation to ingest and retain oral medication.
- Subject has life expectancy of at least 6 months.
- Subject is practicing an acceptable method of contraception (documented in chart). Female subjects (or female partners of male subjects) must either be of nonchildbearing potential (hysterectomy, bilateral oophorectomy, 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).
- Subject is able to understand and comply with protocol requirements and instructions and intend to complete the study as planned.
- Subject has signed and dated written informed consent.
- Chemotherapy naive patients with advanced solid tumors (without brain metastasis or rapid progression within 2 weeks) who are scheduled to receive standard first-line therapy with carboplatin and paclitaxel every 21 days.
- Adequate hematologic, hepatic and renal function.
Exclusion criteria:
- Any clinically relevant abnormality, other than cancer, identified on the screening examination, or any other medical condition or circumstance, which in the opinion of the Investigator, makes the subject unsuitable for participation in the study and/or would make the patient's data difficult to interpret.
- 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.
- Subjects with known pre-existing cardiac disease, including congestive heart failure, arrhythmias requiring treatment, or myocardial infarction within the preceding 3 months.
- Subjects with abnormal resting 12-lead ECG at screening that would indicate preexisting cardiac disease, as noted in exclusion criterion 3.
- Subjects with known clotting disorder associated with hypercoaguability.
- Subject has consumed aspirin, aspirin-containing compounds, salicylates, 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.
- Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication.
- Subject has consumed liquid antacids (e.g. Maalox, Mylanta, Amphogel, milk of magnesia), chewable antacids (e.g. TUMS) or calcium supplements within 48 hours of the first dose of study medication, and/or will require these medications during the study.
- 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.
- Any history of drug-induced thrombocytopenia (e.g., quinine).
- Systemic anti-coagulant use within 4 weeks prior to study entry.
- Consumption of any herbal or dietary supplements, excluding vitamin or mineral supplements (See Exclusion 8 for calcium supplements), within 1 week of the study start.
- Female subjects who are lactating or have a positive beta-hCG at screening.
- 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.
- History of platelet or bleeding disorders.
- Patients using aspirin, aspirin-containing compounds, salicylates, antacids, rosuvastatin, pravastatin, non-steroidal anti-inflammatory drugs for greater than 3 days during and within 3 weeks prior to the study.
- Females who are pregnant or breastfeeding.
Trial location(s)
Location
GSK Investigational Site
Colorado Springs, Colorado, United States, 80907
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Boca Raton, Florida, United States, 33428
Status
Study Complete
Location
GSK Investigational Site
Savannah, Georgia, United States, 31405
Status
Study Complete
Location
GSK Investigational Site
Hattiesburg, Mississippi, United States, 39401
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Freiburg, Baden-Wuerttemberg, Germany, 79106
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Babylon, New York, United States, 11702
Status
Study Complete
Location
GSK Investigational Site
Greenbrae, California, United States, 94904-2007
Status
Study Complete
Location
GSK Investigational Site
Capital Federal, Buenos Aires, Argentina, C1405BCK
Status
Recruiting
Location
GSK Investigational Site
Los Angeles, California, United States, 90033
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Jonesboro, Arkansas, United States, 72401
Status
Study Complete
Location
GSK Investigational Site
Mayfield Heights, Ohio, United States, 44124
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Long Beach, California, United States, 90813
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Minneapolis, Minnesota, United States, 55455
Status
Study Complete
Location
GSK Investigational Site
Leicester, United Kingdom, LE1 5WW
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Chelmsford, Essex, United Kingdom, CM1 7ET
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Baltimore, Maryland, United States, 21237-3998
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Bryan, Texas, United States, 77802
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Colchester, United Kingdom, CO3 3NB
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Hollywood, Florida, United States, 33021
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Campobasso, Molise, Italy, 86100
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Truro, Cornwall, United Kingdom, TR1 3LJ
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Ogden, Utah, United States, 84403
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Tucson, Arizona, United States, 85715
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Newark, Delaware, United States, 19718
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Hyderabad, Andhra Pradesh, India, 500482
Status
Study Complete
Location
GSK Investigational Site
Trier, Rheinland-Pfalz, Germany, 54290
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Akron, Ohio, United States, 44304
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Las Vegas, Nevada, United States, 89102
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Buenos Aires, Argentina, C1416DRW
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Toledo, Ohio, United States, 43614-5809
Status
Study Complete
Location
GSK Investigational Site
Tupelo, Mississippi, United States, 38801
Status
Study Complete
Location
GSK Investigational Site
Tamarac, Florida, United States, 33321
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Durham, North Carolina, United States, 27707
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Buenos Aires, Buenos Aires, Argentina, 1425
Status
Recruiting
Location
GSK Investigational Site
Los Angeles, California, United States, 90095
Status
Terminated/Withdrawn
Location
GSK Investigational Site
La Plata, Buenos Aires, Argentina, 1900
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Hemer, Nordrhein-Westfalen, Germany, 58675
Status
Study Complete
Location
GSK Investigational Site
Metairie, Louisiana, United States, 70006
Status
Study Complete
Location
GSK Investigational Site
Grosshansdorf, Schleswig-Holstein, Germany, 22927
Status
Study Complete
Location
GSK Investigational Site
New York, New York, United States, 10032
Status
Terminated/Withdrawn
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
Study complete
Actual primary completion date
Not applicable
Actual study completion date
2007-28-02
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
Participate in clinical trial
Access to clinical trial data by researchers
Visit website