Prevention of Thrombocytopenia in Glioblastoma Patients

• Status: Terminated
• Trial end date: 2017-12-14
• Target enrollment: 0
• Participant gender: All

Summary

Chemotherapy used in the treatment of primitive tumors of the central nervous system has a particularly important platelet toxicity compared to chemotherapy used for treatment of other tumors. Chemotherapy postponed for toxicity is often due to thrombocytopenia (TP). The TP and/or the other anomalies of coagulation, which can be spontaneous (Rogers, 2004) or induced (Gerber, 2006) can have dramatic consequences:

• specifically neurological (intratumoral bleeding with particularly important neovascularization) with a functional aggravation and sometimes involvement of vital prognosis,

• digestive (Garcia-Rodiguez, 2001) in patients receiving long term treatment with corticoids (potential gastric toxicity).

The encouraging results from the EORTC/NCIC trial by Stupp (median survival among patients with newly diagnosed glioblastoma is 14.6 months with an estimated 5-year survival of 9, 8%), has changed the standard of care of these patients (Stupp et al., 2009). Patients with newly diagnosed, histologically confirmed glioblastoma receive radiotherapy (2 Gy given 5 days per week for 6 weeks, for a total of 60 Gy) plus continuous daily Temozolomide (75 mg per square meter of body-surface area per day, 7 days per week from the first to the last day of radiotherapy), followed by six cycles of adjuvant Temozolomide (TMZ) (150 to 200 mg per square meter for 5 days during each 28-day cycle). The Stupp regimen is currently the treatment of reference for glioblastoma and is used as a basis in various clinical studies with new agents.

This study aims to evaluate Romiplostim for the treatment of TP secondary to initial TMZ chemotherapy of glioblastomas.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospital, Lille
• Treatments: Temozolomide

Criteria

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).

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.