Safety and Efficacy Study for Solid Tumor Patients Treated With Eltrombopag

NCT ID: NCT01147809

Last Updated: 2016-04-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 130 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-06-30
• Study Completion Date: 2015-03-31

Brief Summary

The present study is a randomized, blinded, placebo-controlled, two-Phase, sequential cohort, dose finding study to assess the safety and efficacy of eltrombopag in patients with solid tumors receiving gemcitabine monotherapy or the combination of gemcitabine plus carboplatin or cisplatin. Phase I of the study will examine safety and tolerability of various doses of eltrombopag to identify a dose and schedule of eltrombopag. Phase II will confirm that the chosen dose and schedule of eltrombopag from Phase I can deliver clinically meaningful benefit(s) to thrombocytopenic patients by improving platelet numbers.

Conditions

Thrombocytopaenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: DOUBLE

Study Groups

Eltrombopag

Drug: eltrombopag olamine thrombopoietin receptor agonist

Group Type: ACTIVE_COMPARATOR

Eltrombopag olamine

Intervention Type: DRUG

thrombopoietin receptor agonist

Placebo

Other: Placebo Placebo tablets with no active pharmaceutical ingredient

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo tablets with no active pharmaceutical ingredient

Interventions

Eltrombopag olamine

thrombopoietin receptor agonist

Intervention Type: DRUG

Placebo

Placebo tablets with no active pharmaceutical ingredient

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Signed written informed consent.
• Age ≥ 18 years.
• 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 a standard treatment by the investigator. Subjects with only ONE current diagnosis of primary solid tumor will be allowed into the study.
• 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.
• Life expectancy of at least 3 months, in the opinion of the investigator.
• ECOG-Zubrod performance status ≤ 2
• For Phase I: Pre-chemotherapy platelet count ≤ 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.
• For Phase II (Part 1 and 2): Subjects must meet one of the following platelet count entry criteria:

1. Subjects have not started the first cycle in this disease setting and have a platelet count < 150 Gi/L in the screening period as measured within 3 days before Day -5, OR

2. Subjects started chemotherapy for this disease setting and had platelet count < 150 Gi/L on Day 1 in the preceding cycle before entry into the study, OR

3. Platelet count < 100 Gi/L at Day 8 in the preceding cycle before entry into the study, OR

4. Platelet count < 100 Gi/L at Day 15 in the preceding cycle before entry into the study (for subjects receiving Gemcitabine monotherapy) Note: For any of these platelet counts, a repeated platelet count may be allowed only once to ensure that the subject meets the above platelet count criteria and the latest count will be taken for the assessment of eligibility to the study..

• Adequate organ function during screening period defined by the criteria below (adequate baseline organ function):
• SYSTEM LABORATORY VALUES
• Hematologic
• ANC (absolute neutrophil count) ≥1.5 × 109/L
• Hemoglobin ≥9 g/dL
• Prothrombin time (PT/INR) and activated partial thromboplastin time (aPTT) Within 80 to 120% of the normal range
• Hepatic
• Albumin ≥2.5 g/dL
• Serum bilirubin ≤1.5 x ULN AST and ALT

• 3 × ULN without liver metastases
• 5 × ULN if documented liver metastases
• Renal
• Serum Creatinine ≤ 1.2 x ULN
• Subjects with AST, ALT or bilirubin values outside the range(s) in the table due to Gilbert's syndrome or asymptomatic gall stones are not excluded.
• 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.
• 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.
• 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

Subjects meeting any of the following criteria must not be enrolled in the study:

• Lactating females.
• 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 a34 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.
• 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 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.
• Prior surgery within two weeks before study randomization or radiotherapy (RT) within four weeks before study randomization. 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.
• Note: Note: patients with minor surgeries or outpatient procedures (e.g. insertion of central venous catheter) are immediately allowed in the study provided that there were no complications from the procedure or surgery.
• History of prior radiotherapy to more than 20% bone marrow bearing sites.
• History of platelet agglutination abnormality, platelet disorders or dysfunction or bleeding disorder that prevents reliable measurement of platelet counts.
• 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 randomization will be excluded.
• Treated brain metastases are defined
• 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.
• 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.

Note: if subject has performed a CT scan immediately prior to the screening period and CT could not be repeated, an MRI should be performed in the screening period to exclude the development of brain metastases and/or the progression of the pre-existing brain metastatic lesion(s).

• 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.
• 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).
• Subjects with known Hepatitis B, hepatitis C or Human Immunodeficiency Virus (HIV). Subjects with Gilbert's Syndrome are permitted into the study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Sedona, Arizona, United States

GSK Investigational Site

Hot Springs, Arkansas, United States

GSK Investigational Site

Rancho Cucamonga, California, United States

GSK Investigational Site

Norwich, Connecticut, United States

GSK Investigational Site

Jacksonville, Florida, United States

GSK Investigational Site

New Port Richey, Florida, United States

GSK Investigational Site

Rome, Georgia, United States

GSK Investigational Site

Savannah, Georgia, United States

GSK Investigational Site

Wichita, Kansas, United States

GSK Investigational Site

Bethesda, Maryland, United States

GSK Investigational Site

Rockville, Maryland, United States

GSK Investigational Site

Columbia, Missouri, United States

GSK Investigational Site

Las Vegas, Nevada, United States

GSK Investigational Site

Cherry Hill, New Jersey, United States

GSK Investigational Site

Albany, New York, United States

GSK Investigational Site

Greensboro, North Carolina, United States

GSK Investigational Site

Bend, Oregon, United States

GSK Investigational Site

Philadelphia, Pennsylvania, United States

GSK Investigational Site

Wynnewood, Pennsylvania, United States

GSK Investigational Site

Providence, Rhode Island, United States

GSK Investigational Site

Providence, Rhode Island, United States

GSK Investigational Site

Greenville, South Carolina, United States

GSK Investigational Site

Arlington, Texas, United States

GSK Investigational Site

Austin, Texas, United States

GSK Investigational Site

Bedford, Texas, United States

GSK Investigational Site

Dallas, Texas, United States

GSK Investigational Site

San Antonio, Texas, United States

GSK Investigational Site

Tyler, Texas, United States

GSK Investigational Site

Norfolk, Virginia, United States

GSK Investigational Site

Edmonds, Washington, United States

GSK Investigational Site

Tacoma, Washington, United States

GSK Investigational Site

Vancouver, Washington, United States

GSK Investigational Site

Yakima, Washington, United States

GSK Investigational Site

Charleroi, , Belgium

GSK Investigational Site

Leuven, , Belgium

GSK Investigational Site

Libramont, , Belgium

GSK Investigational Site

Namur, , Belgium

GSK Investigational Site

Edmonton, Alberta, Canada

GSK Investigational Site

Toronto, Ontario, Canada

GSK Investigational Site

Olomouc, , Czechia

GSK Investigational Site

Prague, , Czechia

GSK Investigational Site

Prague, , Czechia

GSK Investigational Site

Helsinki, , Finland

GSK Investigational Site

Tampere, , Finland

GSK Investigational Site

Freiburg im Breisgau, Baden-Wurttemberg, Germany

GSK Investigational Site

Augsburg, Bavaria, Germany

GSK Investigational Site

Munich, Bavaria, Germany

GSK Investigational Site

Munich, Bavaria, Germany

GSK Investigational Site

Goslar, Lower Saxony, Germany

GSK Investigational Site

Hanover, Lower Saxony, Germany

GSK Investigational Site

Essen, North Rhine-Westphalia, Germany

GSK Investigational Site

Dresden, Saxony, Germany

GSK Investigational Site

Dresden, Saxony, Germany

GSK Investigational Site

Berlin, State of Berlin, Germany

GSK Investigational Site

Berlin, State of Berlin, Germany

GSK Investigational Site

Athens, , Greece

GSK Investigational Site

Athens, , Greece

GSK Investigational Site

Heraklion, Crete, , Greece

GSK Investigational Site

Thessaloniki, , Greece

GSK Investigational Site

Budapest, , Hungary

GSK Investigational Site

Győr, , Hungary

GSK Investigational Site

Kaposvár, , Hungary

GSK Investigational Site

Törökbálint, , Hungary

GSK Investigational Site

Zalaegerszeg, , Hungary

GSK Investigational Site

Madurai, , India

GSK Investigational Site

Pune, , India

GSK Investigational Site

Pune, , India

GSK Investigational Site

Dublin, , Ireland

GSK Investigational Site

Dublin, , Ireland

GSK Investigational Site

Tallaght, Dublin, , Ireland

GSK Investigational Site

Ashkelon, , Israel

GSK Investigational Site

Haifa, , Israel

GSK Investigational Site

Jerusalem, , Israel

GSK Investigational Site

Kfar Saba, , Israel

GSK Investigational Site

Tel Aviv, , Israel

GSK Investigational Site

Zrifin, , Israel

GSK Investigational Site

Modena, Emilia-Romagna, Italy

GSK Investigational Site

Aviano (PN), Friuli Venezia Giulia, Italy

GSK Investigational Site

Milan, Lombardy, Italy

GSK Investigational Site

Sassari, Sardinia, Italy

GSK Investigational Site

Pisa, Tuscany, Italy

GSK Investigational Site

Bialystok, , Poland

GSK Investigational Site

Konin, , Poland

GSK Investigational Site

Olsztyn, , Poland

GSK Investigational Site

Poznan, , Poland

GSK Investigational Site

Poznan, , Poland

Countries

United States; Belgium; Canada; Czechia; Finland; Germany; Greece; Hungary; India; Ireland; Israel; Italy; Poland

References

Winer ES, Safran H, Karaszewska B, Richards DA, Hartner L, Forget F, Ramlau R, Kumar K, Mayer B, Johnson BM, Messam CA, Mostafa Kamel Y. Eltrombopag with gemcitabine-based chemotherapy in patients with advanced solid tumors: a randomized phase I study. Cancer Med. 2015 Jan;4(1):16-26. doi: 10.1002/cam4.326. Epub 2014 Aug 28.

Reference Type: DERIVED

PMID: 25165041 (View on PubMed)

Other Identifiers

112765

Identifier Type: -

Identifier Source: org_study_id