Overview

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.