Prevention of Thrombocytopenia in Glioblastoma Patients (PLATUM)

April 23, 2018 updated by: University Hospital, Lille

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Lille, France, 59037 Cedex
        • CHRU de Lille, Hôpital Roger Salengro,Clinique de Neurochirurgie
      • Lyon, France
        • Hôpital Neurologique Pierre Wertheimer, Lyon,
      • Marseille, France
        • AP-HM,Hôpital La Timone, AP-HM, Marseille
      • Paris, France, 75013
        • AH-HP, Hôpital Pitié-Salpêtrière, Service de Neurologie 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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.
Time Frame: one year
one year

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Lille

Investigators

  • Principal Investigator: Emilie Le Rhun, MD, CHRU Lille

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 10, 2014

Primary Completion (Actual)

December 14, 2017

Study Completion (Actual)

December 14, 2017

Study Registration Dates

First Submitted

August 26, 2014

First Submitted That Met QC Criteria

August 27, 2014

First Posted (Estimate)

August 28, 2014

Study Record Updates

Last Update Posted (Actual)

April 25, 2018

Last Update Submitted That Met QC Criteria

April 23, 2018

Last Verified

April 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2011_29
  • 2012-001751-38 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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