Intraarterial Carboplatin + Caelyx vs Intraarterial Carboplatin + Etoposide Phosphate for Progressing Glioblastoma

NCT06356883 | Recruiting Phase 2

• 1 other identifier: 2024-4938
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Glioblastoma Multiforme; Relapse

Outcome Measures

Primary Outcomes (2)

• Tumor Response on MRI using the RANO Criteria

  T1 +/- contrast agent , T2 and FLAIR

  Every 4 weeks until progression per RANO criteria; up to 12 months

• Progression-free Survival

  Time elapsed between study entry and progression

  When radiological progression per RANO criteria is reported; through study completion, an average of 6 months

Secondary Outcomes (4)

• Median overall survival

  When death is reported; through study completion, an average of 2 years

• Treatment-related toxicity

  When hematological or non-hematological events are reported, through study completion, an average of 2 year

• Per treatment quality of life assessment

  Every 4 weeks until progression per RANO criteria; up to 12 months

• Incidence of treatment related Neurocognitive decline

  Every 4 weeks until progression per RANO criteria; up to 12 months

Study Arms (2)

IA Carboplatin + IA Caelyx

EXPERIMENTAL

Participants will be treated with IA carboplatin + IA liposomal doxorubicin on each cycle (4-6 weeks), for up to 12 cycles.

Drug: IA Carboplatin + IA Caelyx

IA Carboplatin + IA Etoposide Phosphate

EXPERIMENTAL

Participants will be treated with IA carboplatin + IA etoposide phosphate on each cycle (4-6 weeks), for up to 12 cycles.

Drug: IA Carboplatin + IA Etoposide Phosphate

Interventions

IA Carboplatin + IA Caelyx DRUG

Intraarterial infusion of carboplatin combined with liposomal doxorubicin

IA Carboplatin + IA Caelyx

IA Carboplatin + IA Etoposide Phosphate DRUG

Intraarterial infusion of carboplatin combined with etoposide phosphate

IA Carboplatin + IA Etoposide Phosphate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Performance status: Karnofsky ranging from 60 to 100%.
• Haematopoietic parameters at recruitment:
• Platelet counts \> 100,000/mm3.
• Hemoglobin \> 8 g/dL.
• Absolute neutrophil count \> 1,500/mm3.
• No impaired bone marrow function.
• 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.

You may not qualify if:

• 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.
• Pregnancy (as confirmed by a positive b-HCG) or actively nursing.
• Presence of an uncontrolled systemic infection.

Sponsors & Collaborators

• Université de Sherbrooke: lead

Study Sites (1)

CHUS

Sherbrooke, Quebec, J1H 5N4, Canada

RECRUITING

Related Publications (19)

• Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;352(10):987-96. doi: 10.1056/NEJMoa043330.

  PMID: 15758009 BACKGROUND

• Kroll RA, Neuwelt EA. Outwitting the blood-brain barrier for therapeutic purposes: osmotic opening and other means. Neurosurgery. 1998 May;42(5):1083-99; discussion 1099-100. doi: 10.1097/00006123-199805000-00082.

  PMID: 9588554 BACKGROUND

• Bradbury MW. The developing experimental approach to the idea of a blood-brain barrier. Ann N Y Acad Sci. 1986;481:137-41. doi: 10.1111/j.1749-6632.1986.tb27146.x. No abstract available.

  PMID: 3468853 BACKGROUND

• Fortin D, Salame JA, Desjardins A, Benko A. Technical modification in the intracarotid chemotherapy and osmotic blood-brain barrier disruption procedure to prevent the relapse of carboplatin-induced orbital pseudotumor. AJNR Am J Neuroradiol. 2004 May;25(5):830-4.

  PMID: 15140730 BACKGROUND

• Newton HB, Slivka MA, Volpi C, Bourekas EC, Christoforidis GA, Baujan MA, Slone W, Chakeres DW. Intra-arterial carboplatin and intravenous etoposide for the treatment of metastatic brain tumors. J Neurooncol. 2003 Jan;61(1):35-44. doi: 10.1023/a:1021218207015.

  PMID: 12587794 BACKGROUND

• Newton HB, Figg GM, Slone HW, Bourekas E. Incidence of infusion plan alterations after angiography in patients undergoing intra-arterial chemotherapy for brain tumors. J Neurooncol. 2006 Jun;78(2):157-60. doi: 10.1007/s11060-005-9080-2. Epub 2006 Apr 14.

  PMID: 16614945 BACKGROUND

• Drapeau A, Fortin D. Chemotherapy Delivery Strategies to the Central Nervous System: neither Optional nor Superfluous. Curr Cancer Drug Targets. 2015;15(9):752-68. doi: 10.2174/1568009615666150616123548.

  PMID: 26077730 BACKGROUND

• Go RS, Adjei AA. Review of the comparative pharmacology and clinical activity of cisplatin and carboplatin. J Clin Oncol. 1999 Jan;17(1):409-22. doi: 10.1200/JCO.1999.17.1.409.

  PMID: 10458260 BACKGROUND

• Fortin D, Morin PA, Belzile F, Mathieu D, Pare FM. Intra-arterial carboplatin as a salvage strategy in the treatment of recurrent glioblastoma multiforme. J Neurooncol. 2014 Sep;119(2):397-403. doi: 10.1007/s11060-014-1504-4. Epub 2014 Jun 20.

  PMID: 24947313 BACKGROUND

• Wagner S, Peters O, Fels C, Janssen G, Liebeskind AK, Sauerbrey A, Suttorp M, Hau P, Wolff JE. Pegylated-liposomal doxorubicin and oral topotecan in eight children with relapsed high-grade malignant brain tumors. J Neurooncol. 2008 Jan;86(2):175-81. doi: 10.1007/s11060-007-9444-x. Epub 2007 Jul 20.

  PMID: 17641821 BACKGROUND

• Wolff JE, Trilling T, Molenkamp G, Egeler RM, Jurgens H. Chemosensitivity of glioma cells in vitro: a meta analysis. J Cancer Res Clin Oncol. 1999 Aug-Sep;125(8-9):481-6. doi: 10.1007/s004320050305.

  PMID: 10480340 BACKGROUND

• Bradford R, Koppel H, Pilkington GJ, Thomas DG, Darling JL. Heterogeneity of chemosensitivity in six clonal cell lines derived from a spontaneous murine astrocytoma and its relationship to genotypic and phenotypic characteristics. J Neurooncol. 1997 Sep;34(3):247-61. doi: 10.1023/a:1005704223040.

  PMID: 9258817 BACKGROUND

• Shen F, Chu S, Bence AK, Bailey B, Xue X, Erickson PA, Montrose MH, Beck WT, Erickson LC. Quantitation of doxorubicin uptake, efflux, and modulation of multidrug resistance (MDR) in MDR human cancer cells. J Pharmacol Exp Ther. 2008 Jan;324(1):95-102. doi: 10.1124/jpet.107.127704. Epub 2007 Oct 18.

  PMID: 17947497 BACKGROUND

• Koukourakis MI, Koukouraki S, Fezoulidis I, Kelekis N, Kyrias G, Archimandritis S, Karkavitsas N. High intratumoural accumulation of stealth liposomal doxorubicin (Caelyx) in glioblastomas and in metastatic brain tumours. Br J Cancer. 2000 Nov;83(10):1281-6. doi: 10.1054/bjoc.2000.1459.

  PMID: 11044350 BACKGROUND

• Fortin D. [The blood-brain barrier should not be underestimated in neuro-oncology]. Rev Neurol (Paris). 2004 May;160(5 Pt 1):523-32. doi: 10.1016/s0035-3787(04)70981-9. French.

  PMID: 15269669 BACKGROUND

• Perry JR, Belanger K, Mason WP, Fulton D, Kavan P, Easaw J, Shields C, Kirby S, Macdonald DR, Eisenstat DD, Thiessen B, Forsyth P, Pouliot JF. Phase II trial of continuous dose-intense temozolomide in recurrent malignant glioma: RESCUE study. J Clin Oncol. 2010 Apr 20;28(12):2051-7. doi: 10.1200/JCO.2009.26.5520. Epub 2010 Mar 22.

  PMID: 20308655 BACKGROUND

• Quant EC, Wen PY. Response assessment in neuro-oncology. Curr Oncol Rep. 2011 Feb;13(1):50-6. doi: 10.1007/s11912-010-0143-y.

  PMID: 21086192 BACKGROUND

• Leao DJ, Craig PG, Godoy LF, Leite CC, Policeni B. Response Assessment in Neuro-Oncology Criteria for Gliomas: Practical Approach Using Conventional and Advanced Techniques. AJNR Am J Neuroradiol. 2020 Jan;41(1):10-20. doi: 10.3174/ajnr.A6358. Epub 2019 Dec 19.

  PMID: 31857322 BACKGROUND

• Fortin D. Drug Delivery Technology to the CNS in the Treatment of Brain Tumors: The Sherbrooke Experience. Pharmaceutics. 2019 May 27;11(5):248. doi: 10.3390/pharmaceutics11050248.

  PMID: 31137918 BACKGROUND

MeSH Terms

Conditions

Glioblastoma; Recurrence

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• David Fortin, MD

  Estrie University Integrated Health and Social Services Center - University Hospital of Sherbrooke

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David Fortin, MD

CONTACT

819-346-1110; david.fortin@usherbrooke.ca

Marie-Andrée Roy, Nurse

CONTACT

819-346-1110; marie-andree.roy.s-inf.ciussse-chus@ssss.gouv.qc.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full professor in surgery

Study Record Dates

• First Submitted: March 19, 2024
• First Posted: April 10, 2024
• Study Start: August 1, 2025
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2028
• Last Updated: August 7, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)