Hypofractionated Stereotactic Irradiation (HFSRT) With Pembrolizumab and Bevacizumab for Recurrent High Grade Gliomas

NCT02313272 | Completed Phase 1 Results FDA Drug

• 1 other identifier: MCC-17978
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to see if the addition of the investigation drug called pembrolizumab (Keytruda®) to radiation therapy and bevacizumab (Avastin®) is safe and can help with controlling the growth of tumors, in participants with recurrent high grade glioma.

Conditions

Malignant Glioma

Keywords

neoplasms; high-grade glioma; recurrent glioma; glioma; Hypofractionated Stereotactic Irradiation (HFSRT); Bevacizumab; Pembrolizumab; recurrent high-grade glioma; Grade III malignant glioma; Grade IV malignant glioma; brain and nervous system

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD)

  The pembrolizumab dose used in the dose expansion cohort will be MTD determined from the dose escalation phase. Dose Escalation: The maximum tolerated dose (MTD) is the highest dose of pembrolizumab in combination with bevacizumab after radiation therapy that does not cause unacceptable toxicity in more than one of six patients at that dose level. The MTD is defined as one dose level below the highest toxic dose (i.e., the Dose Limiting Toxicity (DLT) dose).

  Up to 24 months

Secondary Outcomes (1)

• Response Rate (RR)

  Up to 24 months

Study Arms (1)

HFSRT with Pembrolizumab and Bevacizumab

EXPERIMENTAL

Hypofractionated Stereotactic Irradiation (HFSRT). Pembrolizumab intravenous (IV) infusion every 3 weeks. Bevacizumab administered intravenously every 2 weeks.

Radiation: Hypofractionated Stereotactic Irradiation (HFSRT); Drug: Pembrolizumab; Drug: Bevacizumab

Interventions

Hypofractionated Stereotactic Irradiation (HFSRT) RADIATION

Radiation therapy treatment (FSRT) which will be given to participants over 5 days.

HFSRT with Pembrolizumab and Bevacizumab

Pembrolizumab DRUG

Dose Escalation: The dose of pembrolizumab will be escalated per schema in a 3+3 fashion. The starting dose (i.e., dose level 1) will be 100 mg. Dose Expansion: The pembrolizumab dose used in the dose expansion cohort will be maximum tolerated dose (MTD) determined from the dose escalation phase.

Also known as: Keytruda®, MK-3475

HFSRT with Pembrolizumab and Bevacizumab

Bevacizumab DRUG

Initial cycle of bevacizumab must start within 10 days of registering to the trial. It will be given concurrent with radiation therapy. Bevacizumab will be administered intravenously at a dose of 10 mg/kg every 2 weeks. Doses will be adjusted if there is a \> 10% change in weight.

Also known as: Avastin®

HFSRT with Pembrolizumab and Bevacizumab

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 (except anaplastic oligodendroglioma) or IV malignant glioma.
• Documented recurrence by diagnostic biopsy or contrast enhanced magnetic resonance imaging (MRI) performed within 28 days of entry into the trial as per Response Assessment Criteria for High-Grade Gliomas (RANO) Criteria.
• Patients with recurrent WHO Grade III gliomas should have received one prior treatment for recurrent high grade disease.
• Maximum diameter of enhancing tumor (target lesion) should be ≤ 3.5 cm.
• Interval of ≥ 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.
• Interval of ≥ 4 weeks since surgical resection prior to entry into the trial.
• Interval of ≥ 4 weeks after last administration of any investigational agent or prior cytotoxic therapy (except bevacizumab). There should be 14 days interval between the last dose of bevacizumab and first day of treatment on study.
• Age 18 years or older on day of signing informed consent.
• Karnofsky performance status ≥ 70.
• Demonstrate adequate organ function.
• Resting baseline O2 saturation by pulse oximetry of ≥ 92% at rest.
• Must have recovered from the toxic effects of prior therapies.
• Willing and able to provide written informed consent/assent for the trial.
• Life expectancy ≥ 12 weeks.

You may not qualify if:

• More than 3 recurrences of high grade glioma.
• Has anaplastic oligodendroglioma.
• Has received reradiation 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.
• Infratentorial, or leptomeningeal evidence of recurrent disease.
• Recurrent or persistent tumor (enhancing area) greater than 3.5 cm in maximum diameter.
• Prior treatment with Gliadel unless it was administered as first line treatment and ≥ 3 months prior to study treatment.
• Unable (due to existent medical condition) or unwilling to have a contrast enhanced MRI of brain.
• Currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of first dose of treatment.
• Diagnosis of immunodeficiency or is receiving systemic immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Physiologic doses of steroid therapy (≤ 10 mg/day prednisone equivalents) is allowed.
• Prior chemotherapy, targeted small molecule therapy, or monoclonal antibody (except bevacizumab) within 4 weeks prior to study Day 1 or has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. Wash out period for bevacizumab is 14 days.
• 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.
• Active autoimmune disease requiring systemic treatment within past 3 months or documented history of clinically severe autoimmune disease, or syndrome that requires systemic steroids or immunosuppressive agents.
• Evidence of interstitial lung disease or active, non-infectious pneumonitis.
• Active infection requiring systemic therapy.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Related Publications (1)

• Bruningk SC, Peacock J, Whelan CJ, Brady-Nicholls R, Yu HM, Sahebjam S, Enderling H. Intermittent radiotherapy as alternative treatment for recurrent high grade glioma: a modeling study based on longitudinal tumor measurements. Sci Rep. 2021 Oct 12;11(1):20219. doi: 10.1038/s41598-021-99507-2.

  PMID: 34642366 DERIVED

MeSH Terms

Conditions

Glioma; Neoplasms; Neurologic Manifestations

Interventions

pembrolizumab; Bevacizumab

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Peter Forsyth, MD
• Organization: Moffitt Cancer Center

peter.forsyth@moffitt.org

813-745-3063

Study Officials

• Solmaz Sahebjam, M.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: December 5, 2014
• First Posted: December 10, 2014
• Study Start: July 28, 2015
• Primary Completion: September 13, 2018
• Study Completion: August 9, 2021
• Last Updated: October 23, 2023
• Results First Posted: October 23, 2023

Record last verified: 2022-12

Locations

US (1)