Prevention of Thrombocytopenia in Glioblastoma Patients

Study Overview
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Brief Summary
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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.

Official Title
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Secondary Prophylaxis Use of Romiplostim for the Prevention of Thrombocytopenia Induced by Temozolomide in Newly Diagnosed Glioblastoma Patients

Conditions
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Thrombocytopenia, Glioblastoma

Intervention / Treatment
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* Drug: Romiplostim


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Romiplostim<br>Romiplostim lyophilized formulation is a white, solide cake that is reconstituted with sterile water for injection. | Drug: Romiplostim<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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glioblastoma, thrombocytopenia, temozolomide, chemotherapy