Hypofractionated Stereotactic Irradiation With Nivolumab, Ipilimumab and Bevacizumab in Patients With Recurrent High Grade Gliomas

NCT02829931 | Completed Phase 1 FDA Drug

• 1 other identifier: MCC-18661
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 2

Brief Summary

The main purpose of this study is to evaluate the safety, and tolerability of nivolumab, ipilimumab, and bevacizumab given in combination with hypofractionated stereotactic re-irradiation of recurrent high grade gliomas.

Conditions

Malignant Glioma

Keywords

recurrent glioma; high grade glioma; head and neck disease; grade III glioma; grade IV glioma; radiation therapy

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Treatment Related Adverse Events

  Safety and tolerability of nivolumab, given in combination with hypofractionated stereotactic re-irradiation of recurrent high grade gliomas.

  Up to 24 months

Secondary Outcomes (3)

• Response Rate

  Up to 36 months

• Overall Survival (OS) Rate at 6 Months

  6 months

• Overall Survival (OS) Rate at 9 Months

  9 months

Study Arms (1)

Combination Therapy

EXPERIMENTAL

Safety Cohort: The first 6 participants will receive Hypofractionated Stereotactic Irradiation (HFSRT) followed by Ipilimumab + Nivolumab + Bevacizumab. Dose Expansion Cohort: All 26 participants will be treated with Hypofractionated Stereotactic Irradiation (HFSRT), followed by Ipilimumab + Nivolumab +Bevacizumab

Radiation: Hypofractionated Stereotactic Irradiation; Drug: Nivolumab; Drug: Bevacizumab; Drug: Ipilimumab

Interventions

Hypofractionated Stereotactic Irradiation RADIATION

Hypofractionated Stereotactic Irradiation (HFSRT) prior to nivolumab.

Also known as: HFSRT, radiation therapy

Combination Therapy

Nivolumab DRUG

Nivolumab intravenously (IV): 240 mg every (q) 3 weeks x 4 months followed by 480 mg X 4 months.

Also known as: OPDIVO

Combination Therapy

Bevacizumab DRUG

Bevacizumab intervenously (IV): 15 mg/kg every (q) 3 weeks when given with Ipilumumab and Nivolumab combination. Dose changed to 10mg/kg every 2 weeks when given with Nivolumab only.

Also known as: Avastin

Combination Therapy

Ipilimumab DRUG

Ipilimumab 1mg/kg intervenously (IV) 200 mg (5 mg/mL) every (q) 3 weeks for 4 months.

Also known as: Yervoy

Combination Therapy

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed diagnosis of World Health Organization (WHO) Grade III or IV malignant glioma.
• Documented recurrence by diagnostic biopsy or contrast enhanced magnetic resonance imaging (MRI) performed within 28 days of entry in to the trial as per Response Assessment in Neuro-Oncology (RANO) criteria.
• Maximum diameter of enhancing tumor (target lesion) should be ≤ 4 cm.
• An interval of at least 6 months after the end of prior radiation therapy is required unless there is a new recurrence outside of the previous radiotherapy treatment field.
• Previous first line treatment with at least standard dose of radiotherapy (total dose ≥ 54 Gy) and temozolomide or Procarbazine, Lomustine, and Vincristine (PCV) for high grade glioma.
• An interval of ≥ 4 weeks since surgical resection prior to start of study treatment.
• An interval of ≥ 4 weeks after the last administration of any investigational agent, bevacizumab, or prior cytotoxic therapy.
• ≥18 years of age on day of signing informed consent.
• Karnofsky performance status of 70 or higher.
• Demonstrate adequate organ function. All screening labs should be performed within 28 days of treatment initiation.
• Resting baseline O2 saturation by pulse oximetry of ≥ 92% at rest.
• Must have recovered from the toxic effects of prior therapies (≤ Grade 1).
• Willing and able to provide written informed consent for the trial.
• Life expectancy ≥ 12 weeks
• Women of childbearing potential (WOCBP) should have a negative urine or serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. WOCBP should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 5 months after the last dose of study medication.

You may not qualify if:

• Has more than three recurrences of high grade glioma. Previous recurrences of low grade glioma is not considered.
• Has received re-radiation to recurrent disease (other than standard frontline adjuvant radiation therapy).
• Recurrent tumors near the brainstem and optic chiasm must not have received prior radiation therapy.
• Has infratentorial, or leptomeningeal evidence of recurrent disease.
• Has recurrent or persistent tumor (enhancing area) greater than 4 cm in maximum diameter.
• Has prior treatment with Gliadel unless it was administered as first line treatment and at least 3 months prior to study treatment.
• Is unable (due to existent medical condition) or unwilling to have a contrast enhanced MRI of brain.
• Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Low doses of steroid therapy (dexamethasone 2mg/day or ≤ 10 mg/day prednisone equivalents) is allowed.
• Has had a prior chemotherapy, targeted small molecule therapy, or monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. This does not include lymphopenia.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
• Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Potential participants with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Potential participants that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Potential participants with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study.
• Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
• Has an active infection requiring systemic therapy.
• Had major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to day 1 of treatment on study.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead

Study Sites (2)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Links

• Moffitt Cancer Center Clinical Trials website

MeSH Terms

Conditions

Glioma

Interventions

Radiotherapy; Nivolumab; Bevacizumab; Ipilimumab

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Therapeutics; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Solmaz Sahebjam, M.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2016
• First Posted: July 12, 2016
• Study Start: August 22, 2016
• Primary Completion: August 11, 2021
• Study Completion: November 22, 2022
• Last Updated: January 19, 2023

Record last verified: 2023-01

Locations

US (2)