Intraarterial Carboplatin + Caelyx vs Intraarterial Carboplatin + Etoposide Phosphate for Progressing Glioblastoma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversité de Sherbrooke
About this trial
The standard of care for glioblastoma (GBM) treatment involves maximal resection followed by concomitant radiotherapy and temozolomide. Progression-free survival (PFS) with this treatment is only 6.9 months and relapse is inevitable. At relapse, there is no consensus regarding the optimal therapeutic strategy. The rationale behind the fact that limited chemotherapy agents are available in the treatment of malignant gliomas is related to the blood-brain barrier (BBB), which impedes drug entry to the brain. Intraarterial (IA) chemotherapy allows to circumvent this. Using IA delivery of carboplatin, can produce responses in 70% of patients for a median PFS of 5 months. Median survival from study entry was 11 months, whereas the overall survival (OS) 23 months. How can the OS and PFS be improved? By combining chemotherapeutic agents with different mechanisms of action.
Study design: In this phase II trial, treatment will be offered at relapse. Surgery will be performed for cytoreduction if it is warranted, followed with a combination IA carboplatin + IA Cealyx (liposomal doxorubicin) or IA carboplatin + IA etoposide phosphate. Toxicity will be assessed according to the NCIC common toxicity criteria. Treatment will consist in either IA carboplatin (400 mg/m\^2) + IA Cealyx (30 mg/m\^2) or IA carboplatin (400 mg/m\^2) + IA etoposide phosphate (400 mg/m\^2) every 4-6 weeks (1 cycle). Up to twelve cycles will be offered.
Outcome measurements: Tumor response will be evaluated using the RANO criteria by magnetic resonance imaging monthly. Primary outcome will PFS and tumor response. Secondary outcome will include median OS, toxicity, quality of life (QOL), neurocognition (NC).
Putting together these data will allow to correlate clinical and radiological response to QOL and NC.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Histological diagnosis of glioblastoma multiforme.
Radiological progression on an MRI scan, according to the RANO criteria, in the context of a known glioblastoma multiforme, already treated with the Stupp protocol of combined radiotherapy-Temozolomide. This implies a measurable disease on MRI.
Prior radiotherapy and temozolomide, as per the Stupp protocol, no sooner than 4 weeks, is permitted.
Eighteen or more years of age.
Disqualifiers
Presence of a severe psychiatric or medical condition that would interfere with treatment administration or study recruitment.
Presence of an active autoimmune disease.
No prior cardiac disease within the past 5 years OR LVEF of at least 50% at baseline ultrasound.
Occurrence of another malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer or in situ cervical carcinoma.
Trial design
Design model
Parallel
Treatments tested in this trial
IA Carboplatin + IA Caelyx
DrugIntraarterial infusion of carboplatin combined with liposomal doxorubicin
IA Carboplatin + IA Etoposide Phosphate
DrugIntraarterial infusion of carboplatin combined with etoposide phosphate
Treatment groups
120 Participants
are divided into 2 treatment groupsGroup A: IA Carboplatin + IA CaelyxExperimental treatment 1 intervention
Group B: IA Carboplatin + IA Etoposide PhosphateExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Tumor Response on MRI using the RANO Criteria
T1 +/- contrast agent , T2 and FLAIR
Time frame
Every 4 weeks until progression per RANO criteria; up to 12 months2
Progression-free Survival
Time elapsed between study entry and progression
Time frame
When radiological progression per RANO criteria is reported; through study completion, an average of 6 monthsSecondary outcomes
1
Median overall survival
Time elapsed between initial diagnosis and death
Time frame
When death is reported; through study completion, an average of 2 years2
Treatment-related toxicity
Recording of adverse events
Time frame
When hematological or non-hematological events are reported, through study completion, an average of 2 year3
Per treatment quality of life assessment
SNAS questionnaire (Sherbrooke neuro assessment scale for quality of life). Scale ranges from 30 to 120; the lower scores indicate better quality of life
Time frame
Every 4 weeks until progression per RANO criteria; up to 12 months4
Incidence of treatment related Neurocognitive decline
MOCA questionnaire (Montreal Cognitive Assessment)
Time frame
Every 4 weeks until progression per RANO criteria; up to 12 monthsSponsors and contacts
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Source ClinicalTrials.gov