Prevention of Thrombocytopenia in Glioblastoma Patients (PLATUM)

University Hospital, Lille

Status and phase

Terminated

Phase 2

Conditions

Glioblastoma

Thrombocytopenia

Treatments

Drug: Romiplostim

Study type

Interventional

Funder types

Other

Identifiers

NCT02227576

2012-001751-38 (EudraCT Number)

2011_29

Details and patient eligibility

About

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.

Enrollment

20 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.