SB-497115 (Oral Thrombopoietin Receptor Agonist) Versus Placebo In Adult Cancer Patients Receiving Chemotherapy

NCT00102726 | Completed Phase 2

• 1 other identifier: 497115/003
• Study Type: interventional
• Target: 183
• Locations: 19 countries
• Sites: 95

Brief Summary

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.

Conditions

Thrombocytopaenia

Keywords

chemotherapy; thrombopoietin; platelets; chemotherapy induced

Outcome Measures

Primary Outcomes (1)

• 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)

  throughout entire study

Secondary Outcomes (9)

• 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

  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

  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

  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

  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

  throughout study

Study Arms (4)

Arm 1

ACTIVE COMPARATOR

SB-497115-GR 50mg. administered orally daily on days 2 through 11 for each 21-day cycle.

Drug: SB497115

Arm 2

ACTIVE COMPARATOR

SB-497115-GR 75 mg administered orally dailey on days 2-11 of each 21-day cycle.

Drug: SB497115

Arm 3

ACTIVE COMPARATOR

SB-497115 100mg administered orally daily on days 2 through 11 of each 21-day cycle.

Drug: SB497115

Placebo Arm

PLACEBO COMPARATOR

Placebo administered orally daily on days 2 through 11 of each 21-day cycle.

Other: Placebo

Interventions

SB497115 DRUG

SB497115/Placebo will be administered for at least 2 cycles. Additional cycles are permited if: 1) chemotherapy is continued, 2) the subject appears to be benefitting from the study drug, and 3) the subject has not encountered greater than moderate toxicity with the study drug. The maximum number of cycles would be 8.

Arm 1; Arm 2; Arm 3

Placebo OTHER

Placebo administered orally daily on days 2 through 11 of each 21-day cycle.

Placebo Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 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.
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (95)

GSK Investigational Site

Tucson, Arizona, 85715, United States

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GSK Investigational Site

Jonesboro, Arkansas, 72401, United States

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GSK Investigational Site

Greenbrae, California, 94904-2007, United States

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GSK Investigational Site

Long Beach, California, 90813, United States

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GSK Investigational Site

Los Angeles, California, 90033, United States

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GSK Investigational Site

Los Angeles, California, 90095, United States

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GSK Investigational Site

Colorado Springs, Colorado, 80907, United States

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GSK Investigational Site

Newark, Delaware, 19718, United States

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GSK Investigational Site

Boca Raton, Florida, 33428, United States

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GSK Investigational Site

Hollywood, Florida, 33021, United States

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GSK Investigational Site

Tamarac, Florida, 33321, United States

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GSK Investigational Site

Savannah, Georgia, 31405, United States

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GSK Investigational Site

Metairie, Louisiana, 70006, United States

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GSK Investigational Site

Baltimore, Maryland, 21237-3998, United States

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Minneapolis, Minnesota, 55455, United States

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Hattiesburg, Mississippi, 39401, United States

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Tupelo, Mississippi, 38801, United States

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Las Vegas, Nevada, 89102, United States

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Babylon, New York, 11702, United States

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New York, New York, 10032, United States

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Durham, North Carolina, 27707, United States

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Akron, Ohio, 44304, United States

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Mayfield Heights, Ohio, 44124, United States

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Toledo, Ohio, 43614-5809, United States

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Bryan, Texas, 77802, United States

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Ogden, Utah, 84403, United States

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Salem, Virginia, 24153, United States

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Buenos Aires, Buenos Aires, 1425, Argentina

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GSK Investigational Site

Capital Federal, Buenos Aires, C1405BCK, Argentina

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GSK Investigational Site

La Plata, Buenos Aires, 1900, Argentina

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Rosario, Santa Fe Province, 2000, Argentina

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Rosario, Santa Fe Province, S2000KZE, Argentina

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Buenos Aires, C1416DRW, Argentina

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Vienna, A-1090, Austria

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Vienna, A-1100, Austria

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Vienna, A-1140, Austria

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Plovdiv, 4000, Bulgaria

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Sofia, 1527, Bulgaria

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Sofia, 1756, Bulgaria

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Sofia, 1784, Bulgaria

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Brno, 656 53, Czechia

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Prague, 180 81, Czechia

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Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

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Regensburg, Bavaria, 93049, Germany

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Hamburg, Hamburg, 21075, Germany

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Marburg, Hesse, 35033, Germany

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Hemer, North Rhine-Westphalia, 58675, Germany

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Trier, Rhineland-Palatinate, 54290, Germany

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Großhansdorf, Schleswig-Holstein, 22927, Germany

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Berlin, State of Berlin, 13353, Germany

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Bad Berka, Thuringia, 99437, Germany

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Budapest, 1529, Hungary

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Székesfehérvár, 8000, Hungary

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Bangalore, 560 034, India

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Hyderabad, Andhra Pradesh, 500482, India

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GSK Investigational Site

Kolkata, 700 054, India

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Vellore, 632 004, India

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Benevento, Campania, 82100, Italy

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Rome, Lazio, 00168, Italy

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Milan, Lombardy, 20141, Italy

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Campobasso, Molise, 86100, Italy

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Mérida, Yucatán, 97500, Mexico

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Lima, Lima Province, Lima 34, Peru

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GSK Investigational Site

Olsztyn, 10-228, Poland

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Poznan, 60-569, Poland

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GSK Investigational Site

Poznan, 61-866, Poland

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GSK Investigational Site

Szczecin, 70-891, Poland

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Wroclaw, 53-413, Poland

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Bucharest, 022328, Romania

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GSK Investigational Site

Moscow, 115 478, Russia

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Moscow, 117997, Russia

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GSK Investigational Site

Moscow, 129301, Russia

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GSK Investigational Site

Moscow Region, 143 423, Russia

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GSK Investigational Site

Saint Petersburg, 197758, Russia

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GSK Investigational Site

Saint Petersburg, 198255, Russia

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GSK Investigational Site

Seoul, 135-710, South Korea

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Seoul, 138-736, South Korea

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GSK Investigational Site

Badalona, 08916, Spain

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Barcelona, 08036, Spain

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GSK Investigational Site

Córdoba, 14004, Spain

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GSK Investigational Site

Madrid, 28006, Spain

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GSK Investigational Site

Santa Cruz de Tenerife, 38320, Spain

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GSK Investigational Site

Santander, 38008, Spain

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GSK Investigational Site

Seville, 41014, Spain

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GSK Investigational Site

Taipei, 100, Taiwan

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GSK Investigational Site

Tau-Yuan County, 333, Taiwan

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GSK Investigational Site

Dnipro, 49102, Ukraine

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GSK Investigational Site

Donetsk, 83092, Ukraine

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GSK Investigational Site

Kyiv, 03115, Ukraine

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GSK Investigational Site

Lviv, 79031, Ukraine

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GSK Investigational Site

Truro, Cornwall, TR1 3LJ, United Kingdom

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GSK Investigational Site

Chelmsford, Essex, CM1 7ET, United Kingdom

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GSK Investigational Site

Colchester, CO3 3NB, United Kingdom

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GSK Investigational Site

Dundee, DD1 9SY, United Kingdom

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GSK Investigational Site

Leicester, LE1 5WW, United Kingdom

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Related Publications (2)

• Hayes S, Mudd PN Jr, 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 Jun;71(6):1507-20. doi: 10.1007/s00280-013-2150-9. Epub 2013 Apr 6.

  PMID: 23564375 BACKGROUND

• 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 Oct;26(10):2339-46. doi: 10.1185/03007995.2010.510051.

  PMID: 20735290 BACKGROUND

MeSH Terms

Conditions

Thrombocytopenia; Jacobs syndrome

Interventions

eltrombopag

Condition Hierarchy (Ancestors)

Blood Platelet Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Cytopenia

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2005
• First Posted: February 2, 2005
• Study Start: February 1, 2005
• Primary Completion: February 1, 2007
• Study Completion: February 1, 2007
• Last Updated: March 23, 2017

Record last verified: 2017-03

Locations

GB (5); UA (4); ME (1); RO (1); ES (7); US (27); PE (1); BU (4); PL (5); HU (2); AR (6); IT (4); KR (2); IN (4); CZ (2); RU (6); AU (3); DE (9); TW (2)