IA Carboplatin + IA CaelyxIA Carboplatin + IA Etoposide Phosphate
IA Carboplatin + IA Caelyx: Intraarterial infusion of carboplatin combined with liposomal doxorubicin
IA Carboplatin + IA Etoposide Phosphate: Intraarterial infusion of carboplatin combined with etoposide phosphate
Study summary
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
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
1. Histological diagnosis of glioblastoma multiforme.
2. 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.
3. Prior radiotherapy and temozolomide, as per the Stupp protocol, no sooner than 4 weeks, is permitted.
4. Eighteen or more years of age.
5. Performance status: Karnofsky ranging from 60 to 100%.
6. Haematopoietic parameters at recruitment:
* Platelet counts \> 100,000/mm3.
* Hemoglobin \> 8 g/dL.
* Absolute neutrophil count \> 1,500/mm3.
7. No impaired bone marrow function.
8. Hepatic parameters at recruitment:
* Bilirubin ≤ 2 times normal value.
* AST and ALT ≤ 2 times upper limit of normal (ULN).
* Alkaline phosphatase ≤ 2 times ULN (unless attributed to the tumour).
* No impaired hepatic function.
9. Renal parameters at recruitment:
* No impaired renal function.
* Creatinine no greater than 1.5 fold of the normal value.
* Creatinine clearance \> 30 ml/min.
10. Normal ECG.
11. Written informed consent obtained.
* Patients should be either sterile or else use a contraceptive strategy (for at least 2 months prior to study accruals).
Exclusion Criteria:
1. Presence of a severe psychiatric or medical condition that would interfere with treatment administration or study recruitment.
2. Presence of an active autoimmune disease.
3. No prior cardiac disease within the past 5 years OR LVEF of at least 50% at baseline ultrasound.
4. Occurrence of another malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer or in situ cervical carcinoma.
5. Pregnancy (as confirmed by a positive b-HCG) or actively nursing.
6. Presence of an uncontrolled systemic infection.
Primary outcome measure(s)
Tumor Response on MRI using the RANO Criteria — Every 4 weeks until progression per RANO criteria; up to 12 months T1 +/- contrast agent , T2 and FLAIR
Progression-free Survival — When radiological progression per RANO criteria is reported; through study completion, an average of 6 months Time elapsed between study entry and progression
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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