A Longitudinal Assessment of Tumor Evolution in Patients With Brain Cancer

NCT03425292 | Completed Phase 1 FDA Drug

• 1 other identifier: JWCI-17-0801
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

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.

Conditions

Newly Diagnosed High Grade Glioma

Keywords

immunotherapy; nivolumab; ipilimumab; bevcizumab; temozolomide

Outcome Measures

Primary Outcomes (1)

• Rate of dose limiting toxicities

  treatment-related adverse events that impact administration of treatment

  first 28 days of treatment

Secondary Outcomes (6)

• Treatment-related adverse events

  approximately 7 months

• Tumor response rates

  up to 5 years

• Progression free survival (PFS)

  up to 5 years

• Overall survival (OS)

  up to 5 years

• Levels of immunotherapeutic agents in specimens

  approximately 4 months

Study Arms (6)

1 SOC (closed to enrollment)

ACTIVE COMPARATOR

Standard conformal brain radiation therapy with concurrent and adjuvant temozolomide

Drug: Temozolomide; Radiation: conformal brain radiation therapy

2 Nivo

EXPERIMENTAL

Nivolumab

Drug: Nivolumab monotherapy

3 Nivo-Ipi (closed to enrollment)

EXPERIMENTAL

Nivolumab plus Ipilimumab

Drug: Nivolumab; Drug: Ipilimumab

4 Nivo-Ipi-CCNU-TMZ

EXPERIMENTAL

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

Drug: Nivolumab; Drug: Ipilimumab; Drug: 5-day Temozolomide; Drug: Lomustine

5 Nivo-Ipi-TMZ

EXPERIMENTAL

Nivolumab plus Ipilimumab plus 5-day Temozolomide

Drug: Nivolumab; Drug: Ipilimumab; Drug: 5-day Temozolomide

6 Nivo-Ipi-Bev-TMZ

EXPERIMENTAL

Nivolumab plus Ipilimumab plus Bevacizumab plus 5-day Temozolomide

Drug: Nivolumab; Drug: Ipilimumab; Drug: Bevacizumab; Drug: 5-day Temozolomide

Interventions

Temozolomide DRUG

concomitant and 5-day adjuvant temozolomide

Also known as: temodar

1 SOC (closed to enrollment)

conformal brain radiation therapy RADIATION

standard radiation therapy for newly diagnosed glioblastoma

1 SOC (closed to enrollment)

Nivolumab DRUG

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

Also known as: opdivo

3 Nivo-Ipi (closed to enrollment); 4 Nivo-Ipi-CCNU-TMZ; 5 Nivo-Ipi-TMZ; 6 Nivo-Ipi-Bev-TMZ

Ipilimumab DRUG

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

Also known as: yervoy

3 Nivo-Ipi (closed to enrollment); 4 Nivo-Ipi-CCNU-TMZ; 5 Nivo-Ipi-TMZ; 6 Nivo-Ipi-Bev-TMZ

Bevacizumab DRUG

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

Also known as: avastin

6 Nivo-Ipi-Bev-TMZ

5-day Temozolomide DRUG

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)

Also known as: temodar

5 Nivo-Ipi-TMZ; 6 Nivo-Ipi-Bev-TMZ

Lomustine DRUG

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

Also known as: CCNU

4 Nivo-Ipi-CCNU-TMZ

Nivolumab monotherapy DRUG

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

Also known as: opdivo

2 Nivo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%:

You may not qualify if:

• 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).

Sponsors & Collaborators

• Saint John's Cancer Institute: lead

Study Sites (1)

Saint John's Cancer Institute

Santa Monica, California, 90404, United States

Location

Related Publications (1)

• Kesari S, Wojcinski A, Pabla S, Seager RJ, Gill JM, Carrillo JA, Wagle N, Park DJ, Nguyen M, Truong J, Takasumi Y, Chaiken L, Chang SC, Barkhoudarian G, Kelly DF, Juarez TM. Pre-radiation Nivolumab plus ipilimumab in patients with newly diagnosed high-grade gliomas. Oncoimmunology. 2024 Dec 31;13(1):2432728. doi: 10.1080/2162402X.2024.2432728. Epub 2024 Nov 21.

  PMID: 39572979 DERIVED

MeSH Terms

Interventions

Temozolomide; Nivolumab; Ipilimumab; Bevacizumab; Lomustine

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Nitrosourea Compounds; Urea; Amides; Nitroso Compounds

Study Officials

• Santosh Kesari, MD, PhD

  Saint John's Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Neurosciences

Study Record Dates

• First Submitted: January 21, 2018
• First Posted: February 7, 2018
• Study Start: March 1, 2018
• Primary Completion: September 12, 2022
• Study Completion: October 27, 2023
• Last Updated: November 8, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share
• Time Frame: beginning one year after completion of the trial (no end date)
• Access Criteria: Reasonable request

Locations

US (1)