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Lomustine With and Without Reirradiation for First Progression of Glioblastoma: a Randomized Phase III Study

ConditionFirst Progression of Glioblastoma
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorEuropean Organisation for Research and Treatment of Cancer - EORTC

About this trial

Despite comprehensive multimodal treatment of newly diagnosed glioblastoma, almost all patients suffer from tumour relapse. Currently, no standard of care exists to treat these tumour relapses. Treatment options include repeated surgery (if feasible), systemic therapy (bevacizumab, lomustine, temozolomide re-challenge), reirradiation and best supportive care. Currently, the superiority of combined chemoradiation versus chemotherapy alone remains unproven. Given that lomustine is the standard chemotherapeutic agent for the treatment of recurrent glioblastoma in Europe and the unclear efficacy of reirradiation, we want to explore whether combining lomustine and reirradiation may be a better treatment than lomustine alone. The results of the prospective randomized trial proposed here should demonstrate a significant improvement in overall survival when lomustine is combined with reirradiation in patients with recurrent glioblastoma compared to lomustine alone without adversely affecting quality of survival. The trial will be stopped based on overall survival in a preplanned futility and efficacy interim analysis.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Before patient's enrolment, written informed consent must be given according to ICH/GCP, and national/local regulations.

Patients with first progression or recurrent glioblastoma after standard chemoradiotherapy (any treatment other than use of nitroureas) having occurred at least 6 months after the end of prior radiotherapy

Measurable disease according to RANO criteria with a maximum tumour diameter of 5 cm (local investigator assessment)

In case of surgery for recurrence: fully recovered from surgery, confirmation of recurrence by histology, and patient fit for treatment as per local investigator assessment.

Disqualifiers

Any prior anticancer treatment for recurrent glioblastoma (except surgery)

Significant reduction in thrombocyte and/or leukocyte counts as well as severe renal impairment according to investigator's opinion

History or present acute leukaemia or any myeloid disease

Known hypersensitivity to the active components or excipients of lomustine

Trial design

Design model

Parallel

Treatments tested in this trial

  • Lomustine

    Drug

    Oral administration of Lomustine

  • Reirradiation

    Radiation

    Given at least 6 months after the end of prior radiotherapy

Treatment groups

411 Participants
are divided into 2 treatment groups
Group A: Control groupActive comparator 1 intervention
Group B: Experimental groupExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

Overall Survival (OS)

Defined as the number of days from date of enrolment to the date of death due to any cause

Time frame
From the date of enrolment up to the date of death, assessed up to 40 months after first patient is enrolled

Secondary outcomes

1

Progression Free Survival (PFS)

Events are progressions based on Response Assessment in Neuro Oncology (RANO) criteria as determined by the local investigator .

Time frame
From the date of enrolment up to the date of first objective progression or the date of death whichever occur first, assessed up to 40 months after first patient is enrolled
2

Health-related Quality of Life (HRQoL)

HRQoL will be assessed with the EORTC Quality of Life Questionnaire (QLQ-C30) version 3.

Time frame
From the date of enrolment until disease progression, assessed up to 40 months after first patient is enrolled
3

Toxicity profile of lomustine plus reirradiation

Safety according to the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 5.0 for toxicity and Serious Adverse Event reporting.

Time frame
From the date of enrolment until end of study treatment 30 (± 7 days) after last dose, assessed up to 40 months after first patient is enrolled
4

Neurocognitive functioning of lomustine pus reirradiation

Neurocognitive functioning assessed by Mini Mental State Examination (MMSE)

Time frame
From the date of enrolment until end of study treatment 30 (± 7 days) after last dose, assessed up to 40 months after first patient is enrolled

Other outcomes

1

To assess health-related quality of life over time based on the results of 3 different scales (QLQ-C30, QLQ-BN20 and the item list (IL46)).

Changes in HRQoL from baseline in the GHQ/QoL, fatigue, nausea/vomiting, physical, role and social functioning scale scores assessed over time will be evaluated descriptively. Descriptive summaries such as median, range (minimum, maximum), IQR, mean and standard deviation will be provided for all the other scales from the QLQ-C30, QLQ-BN20 and the item list (IL46). For functional and global HRQoL scales, higher scores represent a better level of functioning and are converted to a 0 to 100 scale. For symptom-oriented scales, a higher score represents more severe symptoms.

Time frame
From the date of enrolment until disease progression, assessed up to 40 months after first patient is enrolled

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

European Organisation for Research and Treatment of Cancer - EORTC

Lead sponsor

Swiss Cancer Institute

Collaborator

Source ClinicalTrials.gov
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