IA Carboplatin + Radiotherapy in Relapsing GBM

NCT03672721 | Recruiting Phase 1

• 1 other identifier: 2018-2452
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

Treatment of glioblastoma involves an optimal surgery, followed by a combination of radiation and temozolomide chemotherapy. Progression-free survival (PFS) with this treatment is only 6.9 months and relapse is the norm. 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 limits drug entry to the brain. Intraarterial (IA) chemotherapy allows to circumvent this. Using IA delivery of carboplatin, the investigators have observed responses in 70% of patients for a median PFS of 5 months. Median survival from study entry was 11 months, whereas the overall survival 23 months. How can this be improved? By coupling radiation with a chemotherapeutic which is also a potent radiosensitizer such as carboplatin. Study design: In this phase I/II trial, patients will be treated at recurrence; a surgery will be performed for cytoreduction and to obtain tumor sample, followed with a combination of re-irradiation and IA carboplatin chemotherapy. A careful escalation scheme from 1.5Gy/fraction up to 3.5Gy/fraction will allow the investigators to determine the optimal re-irradiation dose (10 fractions of radiation over 2 weeks). Toxicity will be assessed according to the NCIC common toxicity criteria. Combined with radiation, patients will receive 2 treatments of IA carboplatin, 400 mg/m2, 4 hours prior to the first and the sixth radiation fraction. IA treatments will then be continued on a monthly basis, up to a total of 12 months, or until progression. Outcome measurements: Tumor response will be evaluated using the RANO criteria by magnetic resonance imaging monthly. The investigators will also acquire a sequence that enables the measurement of cerebral blood flow, cerebral blood volume and blood vessel permeability that are all relevant to understand the delivery of therapeutics to the CNS. Primary outcome will be OS and PFS. Secondary outcome will be QOL, neurocognition, and carboplatin delivery. In vitro intracellular carboplatin accumulation: Tumor samples from re-operation will be be analyzed for intracellular Pt concentration by ICP-MS. The amount of Pt bound to DNA will be measured. The level of apoptosis will be determined for each of the sample. Putting together these data will allow to correlate clinical and radiological response to QOL, NC (MOCA), and to delivery surrogates for the IA infusion and intracellular penetration of carboplatin.

Conditions

Glioblastoma Multiforme; Relapse

Outcome Measures

Primary Outcomes (1)

• Response on MRI using the RANO Criteria

  T1, T2, FLAIR and a new diffusion protocol

  every 4 weeks until progression per RANO criteria

Secondary Outcomes (3)

• Incidence of treatment related Neurocognitive decline

  Every 4 weeks until progression per RANO criteria

• Quality of life (QOL) using SNAS questionnaire (Sherbrooke neuro assessment scale for quality of life). Scale range from 30 to 120; the lower scores indicate better quality of life.

  Every 4 weeks until progression per RANO criteria

• In vitro intracellular carboplatin accumulation

  Once, 40 hours after surgery

Study Arms (6)

Arm 1: IA Carbo + radiation

EXPERIMENTAL

400 mg/m\^2 carbo + 15 Gy

Drug: IA Carbo+ Radiation

Arm 2: IA Carbo + radiation

EXPERIMENTAL

400 mg/m\^2 carbo + 18 Gy

Drug: IA Carbo+ Radiation

Arm 3: IA Carbo + radiation

EXPERIMENTAL

400 mg/m\^2 carbo + 20 Gy

Drug: IA Carbo+ Radiation

Arm 4: IA Carbo + radiation

EXPERIMENTAL

400 mg/m\^2 carbo + 25 Gy

Drug: IA Carbo+ Radiation

Arm 5: IA Carbo + radiation

EXPERIMENTAL

400 mg/m\^2 carbo + 30 Gy

Drug: IA Carbo+ Radiation

Arm 6: IA Carbo + radiation

EXPERIMENTAL

400 mg/m\^2 carbo + 35 Gy

Drug: IA Carbo+ Radiation

Interventions

IA Carbo+ Radiation DRUG

combination of intraarterial carboplatin + radiation in dose escalation

Arm 1: IA Carbo + radiation; Arm 2: IA Carbo + radiation; Arm 3: IA Carbo + radiation; Arm 4: IA Carbo + radiation; Arm 5: IA Carbo + radiation; Arm 6: IA Carbo + radiation

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, and progressing. This implies a measurable disease on MRI.
• Prior radiotherapy and temozolomide, as per the Stupp protocol, no sooner than 4 weeks, is permitted.
• of age and over
• Performance status: Karnofsky 60-100%
• Haematopoietic parameters at enrolment:
• Platelet counts \> 100,000/mm\^3
• Hemoglobin \> 8 g/dL
• Absolute neutrophil count \> 1,500/mm\^3
• No impaired bone marrow function
• Hepatic parameters at enrolment:
• Bilirubin ≤ 2 times normal value
• AST and ALT ≤ 2 times upper limit of normal (ULN) Alkaline phosphatase ≤ 2 times ULN (unless attributed to tumor)
• No impaired hepatic function
• Renal parameters at enrollment:

You may not qualify if:

• Presence of a severe psychiatric or medical condition that would interfere with treatment administration or study enrolment.
• Presence of an active auto-immune disease.
• Occurrence of another malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• Pregnancy (as objectivated 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 (11)

• Charest G, Paquette B, Fortin D, Mathieu D, Sanche L. Concomitant treatment of F98 glioma cells with new liposomal platinum compounds and ionizing radiation. J Neurooncol. 2010 Apr;97(2):187-93. doi: 10.1007/s11060-009-0011-5. Epub 2009 Sep 17.

  PMID: 19760366 BACKGROUND

• Goffaux P, Boudrias M, Mathieu D, Charpentier C, Veilleux N, Fortin D. Development of a concise QOL questionnaire for brain tumor patients. Can J Neurol Sci. 2009 May;36(3):340-8. doi: 10.1017/s0317167100007095.

  PMID: 19534336 BACKGROUND

• Mathieu D, Fortin D. The role of chemotherapy in the treatment of malignant astrocytomas. Can J Neurol Sci. 2006 May;33(2):127-40. doi: 10.1017/s0317167100004881.

  PMID: 16736721 BACKGROUND

• Charest G, Sanche L, Fortin D, Mathieu D, Paquette B. Glioblastoma treatment: bypassing the toxicity of platinum compounds by using liposomal formulation and increasing treatment efficiency with concomitant radiotherapy. Int J Radiat Oncol Biol Phys. 2012 Sep 1;84(1):244-9. doi: 10.1016/j.ijrobp.2011.10.054. Epub 2012 Jan 26.

  PMID: 22284691 BACKGROUND

• Dea N, Fournier-Gosselin MP, Mathieu D, Goffaux P, Fortin D. Does extent of resection impact survival in patients bearing glioblastoma? Can J Neurol Sci. 2012 Sep;39(5):632-7. doi: 10.1017/s0317167100015377.

  PMID: 22931705 BACKGROUND

• Daigle K, Fortin D, Mathieu D, Saint-Pierre AB, Pare FM, de la Sablonniere A, Goffaux P. Effects of surgical resection on the evolution of quality of life in newly diagnosed patients with glioblastoma: a report on 19 patients surviving to follow-up. Curr Med Res Opin. 2013 Oct;29(10):1307-13. doi: 10.1185/03007995.2013.823858. Epub 2013 Jul 30.

  PMID: 23844725 BACKGROUND

• Charest G, Sanche L, Fortin D, Mathieu D, Paquette B. Optimization of the route of platinum drugs administration to optimize the concomitant treatment with radiotherapy for glioblastoma implanted in the Fischer rat brain. J Neurooncol. 2013 Dec;115(3):365-73. doi: 10.1007/s11060-013-1238-8. Epub 2013 Sep 13.

  PMID: 24026531 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

• Shi M, Fortin D, Sanche L, Paquette B. Convection-enhancement delivery of platinum-based drugs and Lipoplatin(TM) to optimize the concomitant effect with radiotherapy in F98 glioma rat model. Invest New Drugs. 2015 Jun;33(3):555-63. doi: 10.1007/s10637-015-0228-4. Epub 2015 Mar 18.

  PMID: 25784204 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

• Blanchette M, Tremblay L, Lepage M, Fortin D. Impact of drug size on brain tumor and brain parenchyma delivery after a blood-brain barrier disruption. J Cereb Blood Flow Metab. 2014 May;34(5):820-6. doi: 10.1038/jcbfm.2014.14. Epub 2014 Feb 12.

  PMID: 24517973 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

  CRC-CHUS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David Fortin, MD

CONTACT

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

Marie-André Roy, nurse

CONTACT

819-346-1110; maroy.chus@ssss.gouv.qc.ca

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: full professor in surgery

Model Details: Dose escalation study of combined intraarterial carboplatin + radiotherapy. Total number of 6 arms, 5 patients per arms plus 5 patients in the arm determined as the NOAEL: arm 1 = 400 mg/m\^2 carbo + 15 Gy; arm 2 = 400 mg/m\^2 carbo + 18 Gy; arm 3 = 400 mg/m\^2 carbo + 20 Gy; arm 4 = 400 mg/m\^2 carbo + 25 Gy; arm 5 = 400 mg/m\^2 carbo + 30 Gy and arm 6 = 400 mg/m\^2 carbo + 35 Gy.

Study Record Dates

• First Submitted: July 11, 2018
• First Posted: September 14, 2018
• Study Start: July 10, 2018
• Primary Completion: December 10, 2025
• Study Completion (Estimated): June 10, 2026
• Last Updated: August 11, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)