IA Carboplatin + Radiotherapy in Relapsing GBM
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|ClinicalTrials.gov Identifier: NCT03672721|
Recruitment Status : Recruiting
First Posted : September 14, 2018
Last Update Posted : September 14, 2018
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 we improve on this? 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.
|Condition or disease||Intervention/treatment||Phase|
|Glioblastoma Multiforme Relapse||Drug: IA Carbo+ Radiation||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||35 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Dose escalation study of combined intraarterial carboplatin + radiotherapy|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study in Relapsing Glioblastoma of Intraarterial Concurrent Chemoradiation Therapy Using IA Carboplatin|
|Actual Study Start Date :||July 10, 2018|
|Estimated Primary Completion Date :||July 10, 2020|
|Estimated Study Completion Date :||July 10, 2021|
Experimental: IA Carbo + radiation
Intraarterial carboplatin + radiation
Drug: IA Carbo+ Radiation
combination of intraarterial carboplatin + radiation in dose escalation
- Response on MRI using the RANO Criteria [ Time Frame: every 4 weeks until progression per RANO criteria; up to 12 months ]T1, T2, FLAIR and a new diffusion protocol
- Incidence of treatment related Neurocognitive decline [ Time Frame: Every 4 weeks until progression per RANO criteria; up to 12 months ]MOCA questionnaire
- 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. [ Time Frame: Every 4 weeks until progression per RANO criteria; up to 12 months ]SNAS Questionnaire
- In vitro intracellular carboplatin accumulation [ Time Frame: Once, 40 hours after surgery ]samples will then be analysed at one hour intervals for intracellular Pt concentration by Inductively Coupled Plasma Mass Spectrometer (ICP-MS). The amount of Pt bound to DNA will also be measured by ICP-MS. The level of apoptosis will be determined for each of the analysed sample
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03672721
|Contact: David Fortin, MD||819-346-1110 ext email@example.com|
|Contact: Marie-André Roy, nurse||819-346-1110 ext firstname.lastname@example.org|
|Principal Investigator:||David Fortin, MD||CRC-CHUS|