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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
Sponsor:
Information provided by (Responsible Party):
David Fortin, Université de Sherbrooke

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 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

  Show Detailed Description

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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)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine

Drug Information available for: Carboplatin

Arm Intervention/treatment
Experimental: IA Carbo + radiation
Intraarterial carboplatin + radiation
Drug: IA Carbo+ Radiation
combination of intraarterial carboplatin + radiation in dose escalation




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Incidence of treatment related Neurocognitive decline [ Time Frame: Every 4 weeks until progression per RANO criteria; up to 12 months ]
    MOCA questionnaire

  2. 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

  3. 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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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, and progressing. 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. 18 of age and over
  5. Performance status: Karnofsky 60-100%
  6. 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
  7. 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
  8. Renal parameters at enrollment:

    • No impaired renal function
    • Creatinine no greater than 1.5 fold of the normal value
    • Creatinine clearance > 30 ml/min.
  9. Normal ECG
  10. Written informed consent obtained
  11. Patient should be either sterile or else use a contraceptive strategy (for at least 2 months prior to study accrual).

    -

Exclusion Criteria:

  1. Presence of a severe psychiatric or medical condition that would interfere with treatment administration or study enrolment.
  2. Presence of an active auto-immune disease.
  3. 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
  4. Pregnancy (as objectivated by a positive b-HCG) or actively nursing
  5. Presence of an uncontrolled systemic infection

Information from the National Library of Medicine

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


Contacts
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Contact: David Fortin, MD 819-346-1110 ext 13895 david.fortin@usherbrooke.ca
Contact: Marie-André Roy, nurse 819-346-1110 ext 13895 maroy.chus@ssss.gouv.qc.ca

Locations
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Canada, Quebec
CHUS Recruiting
Sherbrooke, Quebec, Canada, J1H 5N4
Contact: David Fortin, MD    819-346-1110 ext 13895    david.fortin@usherbrooke.ca   
Contact: marie-André Roy, nurse    819-346-1110 ext 13895    maroy.chus@ssss.gouv.qc.ca   
Sponsors and Collaborators
Université de Sherbrooke
Investigators
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Principal Investigator: David Fortin, MD CRC-CHUS

Publications of Results:

Other Publications:
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Responsible Party: David Fortin, full professor in surgery, Université de Sherbrooke
ClinicalTrials.gov Identifier: NCT03672721     History of Changes
Other Study ID Numbers: 2018-2452
First Posted: September 14, 2018    Key Record Dates
Last Update Posted: September 14, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Carboplatin
Antineoplastic Agents