Prevention of Thrombocytopenia in Glioblastoma Patients

Glioblastoma Clinical Trial

— PLATUM  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02227576
• Other study ID #: 2011_29
• Secondary ID: 2012-001751-38
• Status: Terminated
• Phase: Phase 2
• First received: August 26, 2014
• Last updated: April 23, 2018
• Start date: July 10, 2014
• Est. completion date: December 14, 2017

Study information

• Verified date: April 2018
• Source: University Hospital, Lille
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 20
• Est. completion date: December 14, 2017
• Est. primary completion date: December 14, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Glioblastoma
• Thrombocytopenia

Intervention

Drug:
• Romiplostim

Locations

Country	Name	City	State
France	CHRU de Lille, Hôpital Roger Salengro,Clinique de Neurochirurgie	Lille
France	Hôpital Neurologique Pierre Wertheimer, Lyon,	Lyon
France	AP-HM,Hôpital La Timone, AP-HM, Marseille	Marseille
France	AH-HP, Hôpital Pitié-Salpêtrière, Service de Neurologie 2	Paris

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Lille

Country where clinical trial is conducted

France, 

References & Publications (8)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Mutter N, Stupp R. Temozolomide: a milestone in neuro-oncology and beyond? Expert Rev Anticancer Ther. 2006 Aug;6(8):1187-204. Review. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Incidence of serious adverse events according to CTCAE 4.0 criteria.		one year
Secondary	Incidence of delayed chemotherapy cycles and the incidence of chemotherapy cycles with dose reduction due to severe TP		one year
Secondary	Number and percentage of patients with TP of grade 3 or grade 4 after receiving Romiplostim.		One year
Secondary	Number and percentage of patients receiving platelets transfusion for TP		one year
Secondary	Incidence and type of adverse events linked to TP episodes during Romiplostim and Temozolomide combined treatment.		one year
Secondary	6 months Progression Free Survival:		one year