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Clinical Trial 18661

Cancer Type:
Interventions:BMS-936558 (Nivolumab); Nivolumab

Study Type: Treatment
Phase of Study: Phase I
Investigators:

  • Solmaz Sahebjam

Call 813-745-6100
or 1-800-679-0775
Overview

Study Title

Phase I Trial of Hypofractionated Stereotactic Irradiation (HFSRT) Combined with Nivolumab, Ipilimumab and Bevacizumab in Patients with Recurrent High Grade Gliomas

Summary

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

Objective

3.1 Primary Objective(s) & Hypothesis(es) - (1) Objective: To evaluate the safety, and tolerability of nivolumab given in combination with hypofractionated stereotactic re-irradiation of recurrent high grade gliomas. Hypothesis: Intravenous administration of nivolumab in combination with hypofractionated stereotactic re-irradiation will have acceptable safety and tolerability. 3.2 Secondary Objective(s) & Hypothesis(es) - (1) Objective: To evaluate the response rate, 6-months survival and 9-months survival in patients with recurrent high grade glioma treated with nivolumab after re-irradiation (HFSRT) of their recurrent tumor. Hypothesis: Combination of nivolumab and hypofractionated stereotactic re-irradiation will augment the response to treatment, 6-months survival and 9-months survival. 3.3 Exploratory Objective - (1) Objective: To explore tissue and imaging biomarkers that may predict tumor response to nivolumab in combination with hypofractionated stereotactic re-irradiation in patients with recurrent high grade gliomas.

Inclusion Criteria

  • 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
  • An interval of ≥ 4 weeks since surgical resection prior to 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.
  • Adequate organ function. All screening labs should be performed within 14 days of treatment initiation.
  • Resting baseline O2 saturation by pulse oximetry of ≥ 92% at rest.
  • 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 within 72 hours prior to receiving the first dose of study medication. 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 120 days after the last dose of study medication.
  • Males should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.

  • Exclusion Criteria

  • More than 3 recurrences of high grade glioma. Previous recurrences of low grade glioma is not considered.
  • 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.
  • Infratentorial, or leptomeningeal evidence of recurrent disease.
  • Recurrent or persistent tumor (enhancing area) greater than 4 cm in maximum diameter.
  • Prior treatment with Gliadel, unless administered as first line treatment and at least 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/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 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.
  • 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.
  • 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. Exceptions: Potential participants with vitiligo or resolved childhood asthma/atopy; Persons that require intermittent use of bronchodilators or local steroid injections; Hypothyroidism stable on hormone replacement or Sjorgen's syndrome.
  • Evidence of interstitial lung disease or active, non-infectious pneumonitis.
  • 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.
  • Requires escalating or chronic supraphysiologic doses of corticosteroids (> 10 mg/day prednisone equivalents).
  • History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with participation for the full duration of the trial, or is not in the best interest of the participant, in the opinion of the treating investigator.
  • Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial.
  • Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
  • Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  • Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C Virus (HCV) (e.g., HCV RNA [qualitative] is detected).
  • Received a live vaccine within 30 days prior to first dose of trial treatment.