Prevention of Thrombocytopenia in Glioblastoma Patients
- Registration Number
- NCT02227576
- Lead Sponsor
- University Hospital, Lille
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 20
- 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).
- 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
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Romiplostim Romiplostim Romiplostim lyophilized formulation is a white, solide cake that is reconstituted with sterile water for injection.
- Primary Outcome Measures
Name Time Method 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. one year
- Secondary Outcome Measures
Name Time Method Incidence of serious adverse events according to CTCAE 4.0 criteria. one year Incidence of delayed chemotherapy cycles and the incidence of chemotherapy cycles with dose reduction due to severe TP one year Number and percentage of patients with TP of grade 3 or grade 4 after receiving Romiplostim. One year Number and percentage of patients receiving platelets transfusion for TP one year Incidence and type of adverse events linked to TP episodes during Romiplostim and Temozolomide combined treatment. one year 6 months Progression Free Survival: one year
Trial Locations
- Locations (4)
AP-HM,Hôpital La Timone, AP-HM, Marseille
🇫🇷Marseille, France
Hôpital Neurologique Pierre Wertheimer, Lyon,
🇫🇷Lyon, France
AH-HP, Hôpital Pitié-Salpêtrière, Service de Neurologie 2
🇫🇷Paris, France
CHRU de Lille, Hôpital Roger Salengro,Clinique de Neurochirurgie
🇫🇷Lille, France