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A Longitudinal Assessment of Tumor Evolution in Patients With Brain Cancer

Primary Purpose

Newly Diagnosed High Grade Glioma

Status

Active

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Temozolomide

conformal brain radiation therapy

Nivolumab

Ipilimumab

Bevacizumab

5-day Temozolomide

Lomustine

Nivolumab monotherapy

About this trial

This is an interventional treatment trial for Newly Diagnosed High Grade Glioma focused on measuring immunotherapy, nivolumab, ipilimumab, bevcizumab, temozolomide

Eligibility Criteria

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

Inclusion Criteria:

Participant has the ability to understand and the willingness to provide a signed and dated informed consent form.
Participant has the willingness to comply with all study procedures and availability for the duration of the study.
Participant is being evaluated for a potential, or known, diagnosis of high grade glioma.
Participant is a candidate for brain surgery or has undergone prior surgery and has not received any additional treatment for high grade glioma.
Participant is male or female, ≥ 18 years of age.
Participant has a Karnofsky Performance Status (KPS) ≥ 60%:

Exclusion Criteria:

Participant has received prior anti-cancer treatment for high grade glioma.
Participant has a diagnosis of immunodeficiency or active autoimmune disease.
Participant is receiving chronic systemic steroid therapy in dosing exceeding 8 mg daily of dexamethasone equivalent or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. Note: This is assessed after surgery, prior to starting drug treatment.
Participant has received a live vaccine within 28 days prior to the first dose of study agent. Examples of live vaccines include, but are not limited to measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), typhoid vaccine, and intranasal influenza vaccines (e.g., FluMist®).
Participant has a severe or uncontrolled medical disorder that would, in the investigator's opinion, impair ability to receive study intervention (i.e., uncontrolled diabetes, chronic renal disease, chronic pulmonary disease or active, uncontrolled infection, psychiatric illness/social situations that would limit compliance with study requirements).
Participant is a female of childbearing potential who is pregnant or nursing.
Participant has a history of thrombotic or hemorrhagic stroke or myocardial infarction within 6 months.
Participant has a history of intestinal perforations, fistula, hemorrhages, and/or hemoptysis ≤ 6 months prior to first study treatment.
Participant has active gastrointestinal bleeding.
Participant has uncontrolled hypertension (systolic blood pressure ≥ 160 mm Hg and/or diastolic blood pressure ≥ 90 mm Hg).

Sites / Locations

Saint John's Cancer Institute

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Active Comparator

Experimental

Arm Label

1 SOC (closed to enrollment)

2 Nivo

3 Nivo-Ipi (closed to enrollment)

4 Nivo-Ipi-CCNU-TMZ

5 Nivo-Ipi-TMZ

6 Nivo-Ipi-Bev-TMZ

Arm Description

Standard conformal brain radiation therapy with concurrent and adjuvant temozolomide

Nivolumab

Nivolumab plus Ipilimumab

Nivolumab plus Ipilimumab plus Lomustine (CCNU) plus 5-day Temozolomide

Nivolumab plus Ipilimumab plus 5-day Temozolomide

Nivolumab plus Ipilimumab plus Bevacizumab plus 5-day Temozolomide

Outcomes

Primary Outcome Measures

Rate of dose limiting toxicities

treatment-related adverse events that impact administration of treatment

Secondary Outcome Measures

Treatment-related adverse events

Toxicity will be assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 4.03.

Tumor response rates

Evidence of anti-tumor activity as measured according to immunotherapy Response Assessment in Neuro-Oncology (iRANO) criteria.

Progression free survival (PFS)

The duration of time from start of treatment until objective tumor response.

Overall survival (OS)

The duration of time from start of treatment to death.

Levels of immunotherapeutic agents in specimens

Immunotherapeutic drug levels in specimens.

Change in clinical molecular profile of tumor tissue after treatment

Comparison of tumor tissue molecular profile generated from before and after study treatment.

Full Information

NCT ID

NCT03425292

First Posted

January 21, 2018

Last Updated

February 17, 2023

Sponsor

Saint John's Cancer Institute

1. Study Identification

Unique Protocol Identification Number

NCT03425292

Brief Title

A Longitudinal Assessment of Tumor Evolution in Patients With Brain Cancer

Official Title

A Longitudinal Assessment of Tumor Evolution in Patients With Brain Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

March 1, 2018 (Actual)

Primary Completion Date

September 12, 2022 (Actual)

Study Completion Date

March 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Saint John's Cancer Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

The purpose of this study is to test the safety and tolerability of the research study drugs nivolumab, ipilimumab, lomustine, bevacizumab, and temozolomide when used following surgery and before standard therapy with radiation and temozolomide in patients with newly diagnosed high grade glioma. Additional aims of the study are to: Find out side effects (good and bad) of study drug combinations. Evaluate any preliminary evidence of anticancer activity of study drug combinations . Evaluate tumor characteristics by collecting brain tumor tissue samples. Measure the amount of nivolumab and ipilimumab in biospecimens. Look at biomarkers in biospecimens.

Detailed Description

Patients having a clinically planned surgical procedure (biopsy or cytoreduction) for a suspected diagnosis of high grade glioma will be approached for participation in this study. Tumor tissue obtained from surgery will be used for histological diagnosis and clinical molecular profiling, and excess tumor tissue will be collected for potential correlative studies. A small sample of blood and CSF for research will also be collected. Once a diagnosis of high grade glioma is confirmed, the patient will be allocated to one of the study arms. Treatment will be started approximately 7-42 days following surgery once the patient has recovered from surgery. Routine clinical evaluations will be performed prior to treatment initiation and throughout treatment as clinically indicated. Radiographic brain imaging will be performed approximately 21-42 after treatment initiation and then routinely for medical management. Tumor response will be assessed according to immunotherapy Response Assessment in Neuro-Oncology (iRANO) Working Group criteria. Treatment may continue until the patient experiences unacceptable toxicity or clear disease progression. The determination of whether to stop treatment due to disease progression will be based on the investigator's evaluation of the patient's clinical and radiographic condition, taking into consideration the interpretation of localized inflammatory responses that can mimic radiographic features of tumor progress. Patients discontinuing treatment will have further medical management as directed by their treating physician. As part of follow-up, if the patient undergoes a surgery, results of clinical molecular profiling will be collected, and excess resected tumor tissue will be collected if available along with blood and CSF for correlative studies. A record of any additional anti-cancer treatments and survival status will be made every three to six months.

6. Conditions and Keywords

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

Newly Diagnosed High Grade Glioma

Keywords

immunotherapy, nivolumab, ipilimumab, bevcizumab, temozolomide

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

90 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

1 SOC (closed to enrollment)

Arm Type

Active Comparator

Arm Description

Standard conformal brain radiation therapy with concurrent and adjuvant temozolomide

Arm Title

2 Nivo

Arm Type

Experimental

Arm Description

Nivolumab

Arm Title

3 Nivo-Ipi (closed to enrollment)

Arm Type

Experimental

Arm Description

Nivolumab plus Ipilimumab

Arm Title

4 Nivo-Ipi-CCNU-TMZ

Arm Type

Experimental

Arm Description

Nivolumab plus Ipilimumab plus Lomustine (CCNU) plus 5-day Temozolomide

Arm Title

5 Nivo-Ipi-TMZ

Arm Type

Experimental

Arm Description

Nivolumab plus Ipilimumab plus 5-day Temozolomide

Arm Title

6 Nivo-Ipi-Bev-TMZ

Arm Type

Experimental

Arm Description

Nivolumab plus Ipilimumab plus Bevacizumab plus 5-day Temozolomide

Intervention Type

Drug

Intervention Name(s)

Temozolomide

Other Intervention Name(s)

temodar

Intervention Description

concomitant and 5-day adjuvant temozolomide

Intervention Type

Radiation

Intervention Name(s)

conformal brain radiation therapy

Intervention Description

standard radiation therapy for newly diagnosed glioblastoma

Intervention Type

Drug

Intervention Name(s)

Nivolumab

Other Intervention Name(s)

opdivo

Intervention Description

nivolumab 240 mg IV every 2 weeks for the first 28-day cycle, then option to modify to 480 mg IV every 4 weeks

Intervention Type

Drug

Intervention Name(s)

Ipilimumab

Other Intervention Name(s)

yervoy

Intervention Description

ipilimumab 1 mg/kg IV every 6 weeks (or every 8 weeks when nivolumab is administered every 4 weeks) for a maximum of 4 doses

Intervention Type

Drug

Intervention Name(s)

Bevacizumab

Other Intervention Name(s)

avastin

Intervention Description

bevacizumab 5 mg/kg IV every 2 weeks (up to 10 mg/kg at treating physician's discretion)

Intervention Type

Drug

Intervention Name(s)

5-day Temozolomide

Other Intervention Name(s)

temodar

Intervention Description

150 mg/m^2 oral, once daily on Days 1-5 of each 28-day cycle (stepwise titration every cycle up to 200 mg/m^2 permitted)

Intervention Type

Drug

Intervention Name(s)

5-day Temozolomide

Other Intervention Name(s)

temodar

Intervention Description

100 mg/m^2 oral, once daily on Days 2-6 of each 6 week course (stepwise titration every cycle up to 200 mg/m^2 permitted)

Intervention Type

Drug

Intervention Name(s)

Lomustine

Other Intervention Name(s)

CCNU

Intervention Description

100 mg/m^2 oral, on Day 1 of each 6 week course

Intervention Type

Drug

Intervention Name(s)

Nivolumab monotherapy

Other Intervention Name(s)

opdivo

Intervention Description

nivolumab 300 mg IV every 2 weeks for the first 28-day cycle, then option to modify to 480 mg IV every 4 weeks

Primary Outcome Measure Information:

Title

Rate of dose limiting toxicities

Description

treatment-related adverse events that impact administration of treatment

Time Frame

first 28 days of treatment

Secondary Outcome Measure Information:

Title

Treatment-related adverse events

Description

Toxicity will be assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 4.03.

Time Frame

approximately 7 months

Title

Tumor response rates

Description

Evidence of anti-tumor activity as measured according to immunotherapy Response Assessment in Neuro-Oncology (iRANO) criteria.

Time Frame

up to 5 years

Title

Progression free survival (PFS)

Description

The duration of time from start of treatment until objective tumor response.

Time Frame

up to 5 years

Title

Overall survival (OS)

Description

The duration of time from start of treatment to death.

Time Frame

up to 5 years

Title

Levels of immunotherapeutic agents in specimens

Description

Immunotherapeutic drug levels in specimens.

Time Frame

approximately 4 months

Title

Change in clinical molecular profile of tumor tissue after treatment

Description

Comparison of tumor tissue molecular profile generated from before and after study treatment.

Time Frame

approximately 6 months to 1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Participant has the ability to understand and the willingness to provide a signed and dated informed consent form. Participant has the willingness to comply with all study procedures and availability for the duration of the study. Participant is being evaluated for a potential, or known, diagnosis of high grade glioma. Participant is a candidate for brain surgery or has undergone prior surgery and has not received any additional treatment for high grade glioma. Participant is male or female, ≥ 18 years of age. Participant has a Karnofsky Performance Status (KPS) ≥ 60%: Exclusion Criteria: Participant has received prior anti-cancer treatment for high grade glioma. Participant has a diagnosis of immunodeficiency or active autoimmune disease. Participant is receiving chronic systemic steroid therapy in dosing exceeding 8 mg daily of dexamethasone equivalent or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. Note: This is assessed after surgery, prior to starting drug treatment. Participant has received a live vaccine within 28 days prior to the first dose of study agent. Examples of live vaccines include, but are not limited to measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), typhoid vaccine, and intranasal influenza vaccines (e.g., FluMist®). Participant has a severe or uncontrolled medical disorder that would, in the investigator's opinion, impair ability to receive study intervention (i.e., uncontrolled diabetes, chronic renal disease, chronic pulmonary disease or active, uncontrolled infection, psychiatric illness/social situations that would limit compliance with study requirements). Participant is a female of childbearing potential who is pregnant or nursing. Participant has a history of thrombotic or hemorrhagic stroke or myocardial infarction within 6 months. Participant has a history of intestinal perforations, fistula, hemorrhages, and/or hemoptysis ≤ 6 months prior to first study treatment. Participant has active gastrointestinal bleeding. Participant has uncontrolled hypertension (systolic blood pressure ≥ 160 mm Hg and/or diastolic blood pressure ≥ 90 mm Hg).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Santosh Kesari, MD, PhD

Organizational Affiliation

Saint John's Cancer Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

Saint John's Cancer Institute

City

Santa Monica

State/Province

California

ZIP/Postal Code

90404

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Undecided

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A Longitudinal Assessment of Tumor Evolution in Patients With Brain Cancer

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