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ThrombocytopeniaPhase 2PLATUMNCT02227576

Prevention of Thrombocytopenia in Glioblastoma Patients

A Phase 2 study testing Romiplostim in people with Thrombocytopenia and Glioblastoma, run by University Hospital, Lille at 4 sites in France.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Thrombocytopenia, Glioblastoma
What is being tested?
Romiplostim
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
4 sitesFrance
Study dates
10 Jul 2014to 14 Dec 2017
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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,
Show all 12Show fewer
  • 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).

Who cannot join

  • 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),
Show all 17Show fewer
  • 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.

Trial locations and contacts

4 sites in 1 country.

France4 sites

  • CHRU de Lille, Hôpital Roger Salengro,Clinique de Neurochirurgie

    Lille, 59037 Cedex

  • Hôpital Neurologique Pierre Wertheimer, Lyon,

    Lyon

  • AP-HM,Hôpital La Timone, AP-HM, Marseille

    Marseille

  • AH-HP, Hôpital Pitié-Salpêtrière, Service de Neurologie 2

    Paris, 75013

Other trials in France

About this study

Official title: 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).
Read more

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.

Being tested
Romiplostim
Keywords
glioblastoma, thrombocytopenia, temozolomide, chemotherapy
Medical subject headings
Thrombocytopenia, Glioblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RomiplostimDrug

Study groups in NCT02227576
Study groupRoleWhat they receive
RomiplostimExperimentalRomiplostim lyophilized formulation is a white, solide cake that is reconstituted with sterile water for injection.
Receives: Drug: Romiplostim

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: one year

Secondary outcomes (6)

  1. Incidence of serious adverse events according to CTCAE 4.0 criteria.

    Measured: one year

  2. Incidence of delayed chemotherapy cycles and the incidence of chemotherapy cycles with dose reduction due to severe TP

    Measured: one year

  3. Number and percentage of patients with TP of grade 3 or grade 4 after receiving Romiplostim.

    Measured: One year

  4. Number and percentage of patients receiving platelets transfusion for TP

    Measured: one year

  5. Incidence and type of adverse events linked to TP episodes during Romiplostim and Temozolomide combined treatment.

    Measured: one year

  6. 6 months Progression Free Survival:

    Measured: one year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Aug 2014 (estimated)
  2. Study start10 Jul 2014
  3. Primary completion14 Dec 2017
  4. Study completion14 Dec 2017

Why it stopped: Study halted for efficacy following the results of the interim analysis provided for in the protocol on 20 patients.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02227576
Sponsor's protocol ID
2011_29
Other IDs
2012-001751-38
Acronym
PLATUM
Status last verified
Apr 2018
First submitted
26 Aug 2014
Last updated
25 Apr 2018
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • 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.

    PubMed 19179423

  • 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.

    PubMed 17108062

  • 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.

    PubMed 9867731

  • 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.

    PubMed 21067381

  • 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.

    PubMed 21434943

  • 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.

    PubMed 20434832

  • 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.

    PubMed 16925485

  • 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.

    PubMed 20697524

  • 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.

    PubMed 31586022

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Romiplostim in people with Thrombocytopenia and Glioblastoma, run by University Hospital, Lille at 4 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 25 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Study halted for efficacy following the results of the interim analysis provided for in the protocol on 20 patients.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02227576, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Apr 2018.

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