Prevention of Thrombocytopenia in Glioblastoma Patients

NCT ID: NCT02227576

Last Updated: 2018-04-25

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-07-10
• Study Completion Date: 2017-12-14

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.

Conditions

Thrombocytopenia; Glioblastoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Romiplostim

Romiplostim lyophilized formulation is a white, solide cake that is reconstituted with sterile water for injection.

Group Type: EXPERIMENTAL

Romiplostim

Intervention Type: DRUG

Interventions

Romiplostim

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Lille

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Emilie Le Rhun, MD

Role: PRINCIPAL_INVESTIGATOR

CHRU LILLE

Locations

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, , France

Countries

France

References

Armstrong TS, Cao Y, Scheurer ME, Vera-Bolanos 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.

Reference Type: BACKGROUND

PMID: 19179423 (View on PubMed)

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. doi: 10.1215/15228517-2006-024. Epub 2006 Nov 15.

Reference Type: BACKGROUND

PMID: 17108062 (View on PubMed)

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. doi: 10.7326/0003-4819-129-11_part_1-199812010-00009.

Reference Type: BACKGROUND

PMID: 9867731 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21067381 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21434943 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20434832 (View on PubMed)

Mutter N, Stupp R. Temozolomide: a milestone in neuro-oncology and beyond? Expert Rev Anticancer Ther. 2006 Aug;6(8):1187-204. doi: 10.1586/14737140.6.8.1187.

Reference Type: BACKGROUND

PMID: 16925485 (View on PubMed)

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. doi: 10.3747/co.v17i4.526.

Reference Type: BACKGROUND

PMID: 20697524 (View on PubMed)

Le Rhun E, Devos P, Houillier C, Cartalat S, Chinot O, Di Stefano AL, Lepage C, Reyns N, Dubois F, Weller M. Romiplostim for temozolomide-induced thrombocytopenia in glioblastoma: The PLATUM trial. Neurology. 2019 Nov 5;93(19):e1799-e1806. doi: 10.1212/WNL.0000000000008440. Epub 2019 Oct 4.

Reference Type: DERIVED

PMID: 31586022 (View on PubMed)

Other Identifiers

2012-001751-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2011_29

Identifier Type: -

Identifier Source: org_study_id