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

Primary Purpose

Glioblastoma, Glioblastoma Multiforme, Glioma, Malignant

Status

Recruiting

Phase

Phase 3

Locations

United States

Study Type

Interventional

Intervention

Repeated Superselective Intraarterial Cerebral infusion (SIACI) of Bevacizumab (Avastin) with Temozolomide and Radiation

Temozolomide and Radiation Alone

About this trial

This is an interventional treatment trial for Glioblastoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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:
i. 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.

Sites / Locations

Lenox Hill Brain Tumor CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

SIACI of Bevacizumab (Avastin) with Temozolomide and Radiation

Standard of care Temozolomide and Radiation

Arm Description

Repeated Superselective Intraarterial Cerebral infusion (SIACI) of Bevacizumab (Avastin) with Temozolomide and Radiation

Standard of care Temozolomide and Radiation

Outcomes

Primary Outcome Measures

Overall survival (OS)

The primary end point will be overall survival (OS). Overall survival is defined as the time from randomization until death due to any cause. Participants who are still alive at the time of analysis will be censored at their last known alive date.

Secondary Outcome Measures

Progression-free survival (PFS)

The secondary end point will be progression-free survival (PFS). PFS is defined from the time of randomization until first documentation of disease progression (according to RANO Criteria), or death from any cause, whichever occurs first. Participants without documented disease progression at the time of analysis will be censored at the time of their last tumor assessment.

Full Information

NCT ID

NCT05271240

First Posted

February 22, 2022

Last Updated

May 26, 2023

Sponsor

Northwell Health

1. Study Identification

Unique Protocol Identification Number

NCT05271240

Brief Title

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

Official Title

A Phase III Randomized Trial of Repeated Superselective Intraarterial Cerebral Infusion (SIACI) of Bevacizumab (Avastin) With Temozolomide and Radiation Compared to Temozolomide and Radiation Alone in Newly Diagnosed Glioblastoma (GBM)

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Recruiting

Study Start Date

April 27, 2022 (Actual)

Primary Completion Date

April 1, 2027 (Anticipated)

Study Completion Date

April 1, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Northwell Health

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

Detailed Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Glioblastoma, Glioblastoma Multiforme, Glioma, Malignant, GBM, Brain Cancer, Glioblastoma, IDH-wildtype, Glioblastoma Multiforme, Adult

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

432 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

SIACI of Bevacizumab (Avastin) with Temozolomide and Radiation

Arm Type

Experimental

Arm Description

Repeated Superselective Intraarterial Cerebral infusion (SIACI) of Bevacizumab (Avastin) with Temozolomide and Radiation

Arm Title

Standard of care Temozolomide and Radiation

Arm Type

Active Comparator

Arm Description

Standard of care Temozolomide and Radiation

Intervention Type

Drug

Intervention Name(s)

Repeated Superselective Intraarterial Cerebral infusion (SIACI) of Bevacizumab (Avastin) with Temozolomide and Radiation

Other Intervention Name(s)

IA BV+TMZ/RT, Intraarterial Bevacizumab

Intervention Description

Subjects who are assigned to the IA BV+TMZ/RT group (Treatment Group), in addition to your standard of care cancer treatment, you will have a dose of bevacizumab delivered directly to your brain through superselective intra-cranial intra-arterial catheterization of the arteries that supply blood to your brain tumor along with the start of the initial 42 day oral temozolomide treatment. IA BV will be repeated every three months for a total of 3 infusions.

Intervention Type

Drug

Intervention Name(s)

Temozolomide and Radiation Alone

Other Intervention Name(s)

TMZ/RT alone

Intervention Description

Subjects who are assigned to the TMZ/RT alone group (Control Group) you will receive standard of care cancer treatment that involves a daily oral dose of temozolomide for 42 days with radiation to the tumor followed by 28 days of rest and then repeated maintenance treatment cycles of daily oral temozolomide 5 days on and 23 days off.

Primary Outcome Measure Information:

Title

Overall survival (OS)

Description

Time Frame

62 months

Secondary Outcome Measure Information:

Title

Progression-free survival (PFS)

Description

Time Frame

62 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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: i. 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

John Boockvar, MD

Phone

212-434-3900

jboockvar@northwell.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Tamika Wong, MPH

Phone

212-434-4836

twong4@northwell.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

John Boockvar, MD

Organizational Affiliation

Feinstein Institute for Medical Research/Lenox Hill Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Lenox Hill Brain Tumor Center

City

New York

State/Province

New York

ZIP/Postal Code

10075

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

John Boockvar, MD

Phone

212-434-3900

jboockvar@northwell.edu

First Name & Middle Initial & Last Name & Degree

Tamika Wong, MPH

Phone

212-434-4836

twong4@northwell.edu

First Name & Middle Initial & Last Name & Degree

John Boockvar, MD

First Name & Middle Initial & Last Name & Degree

David Langer, MD

First Name & Middle Initial & Last Name & Degree

Rafael Ortiz, MD

First Name & Middle Initial & Last Name & Degree

Tamika Wong, MPH

First Name & Middle Initial & Last Name & Degree

Olivia Albers, NP

First Name & Middle Initial & Last Name & Degree

Amy McKewon, NP

12. IPD Sharing Statement

Learn more about this trial

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

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