A Longitudinal Assessment of Tumor Evolution in Patients With Brain Cancer

Newly Diagnosed High Grade Glioma Clinical Trial

Official title:

A Longitudinal Assessment of Tumor Evolution in Patients With Brain Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03425292
• Other study ID #: JWCI-17-0801
• Status: Completed
• Phase: Phase 1
• Start date: March 1, 2018
• Est. completion date: October 27, 2023

Study information

• Verified date: November 2023
• Source: Saint John's Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: October 27, 2023
• Est. primary completion date: September 12, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Participant has the ability to understand and the willingness to provide a signed and dated informed consent form.

2. Participant has the willingness to comply with all study procedures and availability for the duration of the study.

3. Participant is being evaluated for a potential, or known, diagnosis of high grade glioma.

4. Participant is a candidate for brain surgery or has undergone prior surgery and has not received any additional treatment for high grade glioma.

5. Participant is male or female, = 18 years of age.

6. Participant has a Karnofsky Performance Status (KPS) = 60%:

Exclusion Criteria:

1. Participant has received prior anti-cancer treatment for high grade glioma.

2. Participant has a diagnosis of immunodeficiency or active autoimmune disease.

3. 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.

4. 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®).

5. 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).

6. Participant is a female of childbearing potential who is pregnant or nursing.

7. Participant has a history of thrombotic or hemorrhagic stroke or myocardial infarction within 6 months.

8. Participant has a history of intestinal perforations, fistula, hemorrhages, and/or hemoptysis = 6 months prior to first study treatment.

9. Participant has active gastrointestinal bleeding.

10. Participant has uncontrolled hypertension (systolic blood pressure = 160 mm Hg and/or diastolic blood pressure = 90 mm Hg).

Related Conditions & MeSH terms

• Brain Neoplasms
• Newly Diagnosed High Grade Glioma

Intervention

Drug:
• Temozolomide
concomitant and 5-day adjuvant temozolomide

Radiation:
• conformal brain radiation therapy
standard radiation therapy for newly diagnosed glioblastoma

Drug:
• Nivolumab
nivolumab 240 mg IV every 2 weeks for the first 28-day cycle, then option to modify to 480 mg IV every 4 weeks
• Ipilimumab
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
• Bevacizumab
bevacizumab 5 mg/kg IV every 2 weeks (up to 10 mg/kg at treating physician's discretion)
• 5-day Temozolomide
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)
• 5-day Temozolomide
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)
• Lomustine
100 mg/m^2 oral, on Day 1 of each 6 week course
• Nivolumab monotherapy
nivolumab 300 mg IV every 2 weeks for the first 28-day cycle, then option to modify to 480 mg IV every 4 weeks

Locations

Country	Name	City	State
United States	Saint John's Cancer Institute	Santa Monica	California

Sponsors (1)

Lead Sponsor	Collaborator
Saint John's Cancer Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of dose limiting toxicities	treatment-related adverse events that impact administration of treatment	first 28 days of treatment
Secondary	Treatment-related adverse events	Toxicity will be assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 4.03.	approximately 7 months
Secondary	Tumor response rates	Evidence of anti-tumor activity as measured according to immunotherapy Response Assessment in Neuro-Oncology (iRANO) criteria.	up to 5 years
Secondary	Progression free survival (PFS)	The duration of time from start of treatment until objective tumor response.	up to 5 years
Secondary	Overall survival (OS)	The duration of time from start of treatment to death.	up to 5 years
Secondary	Levels of immunotherapeutic agents in specimens	Immunotherapeutic drug levels in specimens.	approximately 4 months
Secondary	Change in clinical molecular profile of tumor tissue after treatment	Comparison of tumor tissue molecular profile generated from before and after study treatment.	approximately 6 months to 1 year