SECONDARY PROPHYLAXIS USE OF ROMIPLOSTIM FOR THE PREVENTION OF THROMBOCYTOPENIA IN NEWLY DIAGNOSED GLIOBLASTOMA PATIENTS

Phase 1

Conditions: MedDRA version: 14.1Level: LLTClassification code 10043559Term: Thrombocytopenia toxicSystem Organ Class: 100000004851
MedDRA version: 14.1Level: PTClassification code 10018336Term: GlioblastomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2012-001751-38-FR

Lead Sponsor: CHRU de Lille

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 35

Inclusion Criteria

•Histological proof of newly diagnosed glioblastoma,
•Age: 18 and older,
•Information to patient and signed consent form,
•Indication for a « Stupp » protocol (cerebral focal radiotherapy and concomitant TMZ followed by adjuvant TMZ – 6 cycles),
•Patient with grade 3 or 4 TP during Temozolomide chemotherapy, regardless of when the onset of TP was: after completion of concomitant RT/CT, before adjuvant CT or during adjuvant CT and only if a minimum of 2 cycles are still planned,
•Normal initial platelets count (> 100 000/mm3) before the start of Temozolomide during the RT/CT concomitant phase,
•Adequate haematological, renal, hepatic function at the time of inclusion visit,
•ECOG PS 0-2 (patients unable to walk because of a paralysis and who are up in a wheel chair will be considered as ambulatory for the evaluation of the ECOG performance status),
•Life expectancy > 2 months,
•Patients covered by the French Health Insurance System,
•Negative pregnancy test at the time of inclusion visit,
•If required, effective contraception respecting criteria of CPMP/ICH/286/95 (such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or vasectomised partner).

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 35
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 35

Exclusion Criteria

•Concomitant radiotherapy (Romiplostim will be started after the completion of the RT/CT concomitant phase),
•Other malignancies (prior hx malignancies),
•Any anterior systemic chemotherapy,
•Any known coagulation disease or known haematological disease even if resolved. Known hypercoagulate state (e.g., factor V Leiden, protein C defiency, protein S deficiency, PT 20201, antiphospholipid antibody syndrome…),
•Prior Romiplostim exposure or prior exposure to other TPO mimetics,
•History of thromboembolic disease < 6 months. Treatment with anticoagulant such as Heparin or antivitamin K (LMWH as prophylactic treatment is authorized),
•Any other hemato-toxicity (anemia, neutropenia) requiring EPO or GCSF,
•Other causes of Temozolomide interruption (non haematological toxicities),
•Known hypersensitivity to any E-coli derived product,
•Participation to any other study during the last 30 days,
•Refusal to give written informed consent,
•Pregnancy or nursing,
•For all men and women of childbearing potential: Refusal or inability to use effective means of contraception,
•Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial,
•Persons protected by a legal regime (guardianship, trusteeship),
•Patients in emergency situations,
•Patients kept in detention.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the incidence of completed chemotherapy cycles;Secondary Objective: •To evaluate the safety of Romiplostim in treating Chemotherapy Induced Thrombocytopenia (CIT) in newly diagnosed glioblastoma patients receiving myelosuppressive chemotherapy by Temozolomide (TMZ).<br>•To determine the incidence of delayed chemotherapy cycles and the incidence of chemotherapy cycles with dose reduction due to severe TP.<br>•To describe the incidence of TP resolution during Romiplostim treatment period. <br>•To determine the incidence of platelets transfusion for TP during Romiplostim treatment. <br>•To describe the adverse events during Romiplostim and Temozolomide combined treatment.<br>•To determine the 6 months Progression Free Survival. <br>;Primary end point(s): Proportion of patients receiving 100% of the planned TMZ dosage in the whole Stupp protocol. The primary endpoint will consider dose reduction and dose delay.;Timepoint(s) of evaluation of this end point: 34 weeks

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): •Incidence of serious adverse events according to CTCAE 4.0 criteria.<br>•Incidence of chemotherapy cycles with dose reduction and reasons for dose reduction, incidence of postponed cycles of chemotherapy, reasons for delay and number of delayed days. <br>•Number and percentage of patients with TP of grade 3 or grade 4 after receiving Romiplostim.<br>•Number and percentage of patients receiving platelets transfusion for TP.<br>•Incidence and type of adverse events linked to TP episodes during Romiplostim and Temozolomide combined treatment.<br>•6 months Progression Free Survival: The progression will be defined according to the RANO criteria. The progression will not be reported as an adverse event if it is related to the disease.<br>;Timepoint(s) of evaluation of this end point: 34 weeks