PLATUM: Prevention of Thrombocytopenia in Glioblastoma Patients
Study Details
Study Description
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:
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specifically neurological (intratumoral bleeding with particularly important neovascularization) with a functional aggravation and sometimes involvement of vital prognosis,
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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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Romiplostim Romiplostim lyophilized formulation is a white, solide cake that is reconstituted with sterile water for injection. |
Drug: Romiplostim
|
Outcome Measures
Primary Outcome Measures
- 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
- 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]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Histological proof of newly diagnosed glioblastoma,
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Age: 18 and older,
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Information to patient and signed consent form,
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Indication for a " Stupp " protocol (cerebral focal radiotherapy and concomitant TMZ followed by adjuvant TMZ - 6 cycles),
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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,
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Normal initial platelets count (> 100 000/mm3) before the start of Temozolomide during the RT/CT concomitant phase,
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Adequate haematological, renal, hepatic function at the time of inclusion visit,
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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),
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Life expectancy > 2 months,
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Patients covered by the French Health Insurance System,
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Negative pregnancy test at the time of inclusion visit,
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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:
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Concomitant radiotherapy (Romiplostim will be started after the completion of the RT/CT concomitant phase),
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Other malignancies (prior hx malignancies),
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Any anterior systemic chemotherapy,
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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…),
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Prior Romiplostim exposure or prior exposure to other TPO mimetics,
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History of thromboembolic disease < 6 months. Treatment with anticoagulant such as Heparin or antivitamin K (LMWH as prophylactic treatment is authorized),
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Any other hemato-toxicity (anemia, neutropenia) requiring EPO or GCSF,
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Other causes of Temozolomide interruption (non haematological toxicities),
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Known hypersensitivity to any E-coli derived product,
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Participation to any other study during the last 30 days,
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Refusal to give written informed consent,
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Pregnancy or nursing,
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For all men and women of childbearing potential: Refusal or inability to use effective means of contraception,
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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,
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Persons protected by a legal regime (guardianship, trusteeship),
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Patients in emergency situations,
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Patients kept in detention.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | CHRU de Lille, Hôpital Roger Salengro,Clinique de Neurochirurgie | Lille | France | 59037 Cedex | |
| 2 | Hôpital Neurologique Pierre Wertheimer, Lyon, | Lyon | France | ||
| 3 | AP-HM,Hôpital La Timone, AP-HM, Marseille | Marseille | France | ||
| 4 | AH-HP, Hôpital Pitié-Salpêtrière, Service de Neurologie 2 | Paris | France | 75013 |
Sponsors and Collaborators
- University Hospital, Lille
Investigators
- Principal Investigator: Emilie Le Rhun, MD, CHRU Lille
Study Documents (Full-Text)
None provided.More Information
Publications
- Armstrong TS, Cao Y, Scheurer ME, Vera-Bolaños E, Manning R, Okcu MF, Bondy M, Zhou R, Gilbert MR. Risk analysis of severe myelotoxicity with temozolomide: the effects of clinical and genetic factors. Neuro Oncol. 2009 Dec;11(6):825-32. doi: 10.1215/15228517-2008-120.
- George JN, Raskob GE, Shah SR, Rizvi MA, Hamilton SA, Osborne S, Vondracek T. Drug-induced thrombocytopenia: a systematic review of published case reports. Ann Intern Med. 1998 Dec 1;129(11):886-90. Review.
- Gerber DE, Grossman SA, Zeltzman M, Parisi MA, Kleinberg L. The impact of thrombocytopenia from temozolomide and radiation in newly diagnosed adults with high-grade gliomas. Neuro Oncol. 2007 Jan;9(1):47-52. Epub 2006 Nov 15.
- Kuter DJ, Rummel M, Boccia R, Macik BG, Pabinger I, Selleslag D, Rodeghiero F, Chong BH, Wang X, Berger DP. Romiplostim or standard of care in patients with immune thrombocytopenia. N Engl J Med. 2010 Nov 11;363(20):1889-99. doi: 10.1056/NEJMoa1002625.
- Molineux G. The development of romiplostim for patients with immune thrombocytopenia. Ann N Y Acad Sci. 2011 Mar;1222:55-63. doi: 10.1111/j.1749-6632.2011.05975.x. Review.
- Mutter N, Stupp R. Temozolomide: a milestone in neuro-oncology and beyond? Expert Rev Anticancer Ther. 2006 Aug;6(8):1187-204. Review.
- Oh J, Kutas GJ, Davey P, Morrison M, Perry JR. Aplastic anemia with concurrent temozolomide treatment in a patient with glioblastoma multiforme. Curr Oncol. 2010 Aug;17(4):124-6.
- Sure D, Dunn I, Norden A, Anderson WS. Intracerebral hemorrhage secondary to thrombocytopenia in a patient treated with temozolomide. Clin Neurol Neurosurg. 2010 Oct;112(8):741-2. doi: 10.1016/j.clineuro.2010.04.005.
- 2011_29
- 2012-001751-38