Repeated Superselective Intraarterial Cerebral Infusion (SIACI) of Bevacizumab With Temozolomide and Radiation Compared to Temozolomide and Radiation Alone in Newly Diagnosed GBM

  • STATUS
    Recruiting
  • End date
    Apr 1, 2028
  • participants needed
    432
  • sponsor
    Northwell Health
Updated on 24 May 2022
cancer
intraarterial cerebral infusion
avastin
karnofsky performance status
MRI
neutrophil count
EGFR
bevacizumab
temozolomide
malignant glioma
brain tumor
recurrent malignant glioma
malignant brain tumor
blood urea nitrogen
TERT

Summary

Primary brain cancer kills up to 10,000 Americans a year. These brain tumors are typically treated by surgery, radiation therapy and chemotherapy, either individually or in combination. Present therapies are inadequate, as evidenced by the low 5-year survival rate for brain cancer patients, with median survival at approximately 12 months. Glioma is the most common form of primary brain cancer, afflicting approximately 7,000 patients in the United States each year. These highly malignant cancers remain a significant unmet clinical need in oncology.

The investigators have completed a Phase I clinical trial that has shown that Superselective Intraarterial Cerebral Infusion (SIACI) of Bevacizumab (BV) is safe up to a dose of 15mg/kg in patients with recurrent malignant glioma. Additionally, the investigators have shown in a recently completed Phase I/II clinical trial, that SIACI BV improves the median progression free survival (PFS) from 4-6 months to 11.5 months and overall survival (OS) from 12-15 months to 23 months in patients with newly diagnosed GBM. Therefore, this two-arm, randomized trial (2:1) is a follow up study to these trials and will ask simple questions: Will this repeated SIACI treatment regimen increase progression free survival (PFS-primary endpoint) and overall survival (OS-secondary endpoint) when compared with standard of care in patients with newly diagnosed GBM? Exploratory endpoints will include adverse events and safety analysis as well as quality of life (QOL) assessments. The investigators expect that this project will provide important information regarding the utility of repeated SIACI BV therapy for newly diagnosed GBM and may alter the way these drugs are delivered to our patients in the near future.

Description

Those randomized to the treatment group (IA BV+TMZ/RT )the experimental aspects will include:

  1. Subjects will first be treated with Mannitol prior to IA BV infusion. Mannitol is delivered IA, 12.5 mL over 2 minutes in order to disrupt the blood brain barrier. IA mannitol has been used in several thousand patients in previous studies for the IA delivery of chemotherapy for malignant glioma.
  2. Subjects will then be treated with repeated IA BV. Each patient will receive one dose of IA BV on day 30, followed by chemoradiation. IA BV will be repeated every three months for a total of 3 infusions.

Details
Condition Glioblastoma, Glioblastoma Multiforme, Glioma, Malignant, GBM, Brain Cancer, Glioblastoma, IDH-wildtype, Glioblastoma Multiforme, Adult
Treatment Repeated Superselective Intraarterial Cerebral infusion (SIACI) of Bevacizumab (Avastin) with Temozolomide and Radiation, Temozolomide and Radiation Alone
Clinical Study IdentifierNCT05271240
SponsorNorthwell Health
Last Modified on24 May 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Subject is a male or female 18 years of age or older
Subject has a confirmed diagnosis of GBM according to the 2021 WHO Classification of Tumors of the CNS. Accordingly, eligible GBM patients will comprise only IDH-wild type astrocytomas with microvascular proliferation or necrosis or one or more of 3 genetic parameters (TERT promoter mutations, EGFR gene amplification, or combined gain of entire chromosome 7 and loss of entire chromosome 10)
Subject has a Karnofsky Performance Status (KPS) 70% or greater
Subject has a life expectancy of at least 6 months, in the opinion of the Investigator
Subject must be able to undergo MRI evaluation
Subject meets the following laboratory criteria
White blood count ≥ 3,000/μL ii. Absolute neutrophil count ≥ 1,500/μL iii. Platelets ≥ 100,000/μL iv. Hemoglobin > 10.0 g/dL (transfusion and/or ESA allowed) v. Total bilirubin and alkaline phosphatase ≤ 2x institutional upper limit of normal (ULN) vi. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x ULN vii. Blood urea nitrogen (BUN) and creatinine < 1.5 x ULN
Females of reproductive potential must have a negative serum pregnancy test and be willing to use an acceptable method of birth control
Males of reproductive potential must be willing to use an acceptable method of birth control to ensure effective contraception with partner
Able to understand and willing to sign an institutional review board (IRB)-approved written informed consent document (legally authorized representative permitted)

Exclusion Criteria

Subject has initiated chemotherapy or radiation treatment for diagnosis of or GBM
Subject has an IDH mutant astrocytoma or other non GBM brain tumor according to the 2021 WHO classification of Tumors of the CNS
Subject intends to participate in another clinical trial
Subject has an active infection requiring treatment
Subject has radiographic evidence of multi-focal disease or leptomeningeal dissemination
Subject has a history of other malignancy unless the patient has been disease-free for at least 5 years. Adequately treated basal cell carcinoma or squamous cell skin cancer is acceptable regardless of time, as well as localized prostate carcinoma or cervical carcinoma in situ after curative treatment
Subject has a known positive test for human immunodeficiency virus infection, or active hepatitis B or hepatitis C infection
Subject has a history or evidence of any other clinically significant disorder, condition or disease that would pose a risk to subject safety or interfere with the study evaluation, procedures or completion
Subject, if female, is pregnant or is breast feeding
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