A Study to Assess the Efficacy and Safety of Eltrombopag as a Rescue of Isolated Chemotherapy-induced Thrombocytopenia

A Randomized, Double Blind Placebo-controlled Study to Assess the Efficacy and Safety of Eltrombopag as a Rescue of Isolated Chemotherapy-induced Thrombocytopenia in Patients With Solid Tumor

The purpose of this study is evaluate the efficacy and safety of eltrombopag as a rescue of isolated chemotherapy-induced thrombocytopenia in patients with solid tumor .

Study Overview

• Status: Unknown
• Conditions: Solid Tumor
• Intervention / Treatment: Drug: Eltrombopag; Drug: Placebo

Detailed Description

For the phase III study, a double-blind randomized, placebo controlled, parallel-group design will be conducted to evaluate the efficacy of eltombopag . Each subject will be randomly assigned to either Arm A (eltombopag) or Arm B (placebo) in 2:1 ratio.

The primary objective is to compare the response rates of the two treatment arms, Therefore, the two-proportion z test will be considered and sample size can be chosen to achieve an 95% power for detecting a clinically meaningful difference at level of significance=0.05. A difference of 40% in clinical response is considered of clinically meaningful difference between the two treatment arms (75% for eltombopag vs. 35% for placebo). It requires a total sample of 83 subjects (55 for eltombopag and 28 for placebo). According to the 10% loss of screening failure, 90-100 subjects (60-67 for eltombopag and 30-33 for placebo) will be recruited.

• Study Type: Interventional
• Enrollment (Anticipated): 83
• Phase: Phase 3

Contacts and Locations

Study Locations

• Taiwan
  • Chiayi City, Taiwan
    • Department of Obstetrics & Gynecology and Department of Oncology Chang Gung Memorial Hospital
  • Kaohsiung, Taiwan
    • Department of Obstetrics & Gynecology Chang Gung Memorial Hospital
  • Linkou, Taiwan
    • Division of Gynecologic Oncology, Department of Obstetrics & Gynecology and Division of Oncology Chang Gung Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects aged ≥18 years
• Diagnosed with solid tumor
• On active chemotherapy with combined regimen
• A baseline platelet count of <75,000/μL within 2 days of screening
• Hb ≧ 9.0 g/dL
• ANC ≧ 1,500/uL
• GOT and GPT ≤ 3 x ULN
• Serum bilirubin ≤ 1.5 x ULN
• Albumin ≥ 2.5 g/dL
• Adequate renal function for chemotherapy:

serum creatinine ≤ 1.5 × ULN (CTCAE Grade 1).

• Be able to take oral medicine
• ECOG performance ≤ 2
• Has a negative urine or serum pregnancy test at screening and is willing to use contraceptive measures during medication of this trial (Non-childbearing potential is defined as hysterectomy, bilateral oophorectomy, bilateral salpingectomy, tubal ligation and post-menopausal status) for patients with childbearing potential
• Ability to participate and willingness to give written informed consent and to comply with the study restrictions

Exclusion Criteria:

• Single agent chemotherapy or not having chemotherapy
• Serious cardiac, cerebrovascular, or pulmonary disease that, in the opinion of the investigator, would preclude trial medication
• Severe GI tract obstruction that require continuous NG decompression
• Subjects with hemoglobinopathies, e.g. sickle cell anaemia, thalassemia major
• Any prior history of arterial or venous thrombosis
• Any disease condition associated with active bleeding or requiring anticoagulation, heparin or warfarin
• Pre-existing cardiac disease (congestive heart failure New York Heart Association (NYHA) Grade III/IV), (See Appendix 1), or arrhythmias known to involve the risk of thromboembolic events (e.g. atrial fibrillation), or subjects with a QTc >450 msec.
• Seizure disorder that has not been well controlled
• Pregnant or nursing women
• Thyroid dysfunction not adequately controlled.
• Within 2months prior to entering the study, been received radiotherapy to more than 20% bone marrow bearing sites.
• 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 is due to drugs chemically related to eltrombopag
• Subjects taking anti-neoplastic and immunomodulatory medications (this includes mycophenolate mofetil, thymosine alpha, and extended courses of supraphysiologic doses of steroids)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: eltrombpag; Eligible patients will be enrolled randomly in 2:1 ratio to Investigational Drug (Eltrombopag) arm, 50 mg/day, or placebo arm for 7 days.	Drug: Eltrombopag; This will be a Phase III, randomized, double-blind, placebo-controlled clinical trial. Qualified subjects will be randomly assigned to receive either the test treatment or the placebo at 2:1 ratio. Once subjects are randomized, they will be treated with Arm A: Eltrombopag 50 mg/day (n=55) or Arm B: placebo (n=28) once a day for 7 days.; Other Names: Revolade
Placebo Comparator: Eltrombopag/placebo; Eligible patients will be enrolled randomly in 2:1 ratio to Investigational Drug (Eltrombopag) arm, 50 mg/day, or placebo arm for 7 days	Drug: Placebo; This will be a Phase III, randomized, double-blind, placebo-controlled clinical trial. Qualified subjects will be randomly assigned to receive either the test treatment or the placebo at 2:1 ratio. Once subjects are randomized, they will be treated with Arm A: Eltrombopag 50 mg/day (n=55) or Arm B: placebo (n=28) once a day for 7 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
efficacy of eltrombopag (50mg once daily)	Evaluate the efficacy of eltrombopag (50mg once daily) compared to the placebo by assessment of response rate	up to treatment eltrombopag 7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
safety and feasibility of 7-day eltrombopag	Number of Participants with Chemotherapy-induced thrombocytopenia to assess safety and feasibility to Change from Baseline in use eltrombopag at 7 days	up to treatment eltrombopag 7 days

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital
• Collaborators: Novartis
• Investigators: Principal Investigator: Hung-Hsueh Chou, Clinical Trial Center, Chang Gung Memorial Hospital at Linkou

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Anticipated): March 1, 2019
• Study Completion (Anticipated): August 1, 2019

Study Registration Dates

• First Submitted: March 17, 2014
• First Submitted That Met QC Criteria: March 19, 2014
• First Posted (Estimate): March 21, 2014

Study Record Updates

• Last Update Posted (Actual): October 24, 2017
• Last Update Submitted That Met QC Criteria: October 22, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: eltrombopag , thrombocytopenia, solid tumor
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Platelet Disorders; Thrombocytopenia
• Other Study ID Numbers: 102-4363A3