Clinical Trials /

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

NCT02829931

Description:

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.

Related Conditions:
  • Glioma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Hypofractionated Stereotactic Irradiation With Nivolumab in Patients With Recurrent High Grade Gliomas
  • Official Title: Phase I Trial of Hypofractionated Stereotactic Irradiation (HFSRT) Combined With Nivolumab in Patients With Recurrent High Grade Gliomas

Clinical Trial IDs

  • ORG STUDY ID: MCC-18661
  • NCT ID: NCT02829931

Conditions

  • Malignant Glioma

Interventions

DrugSynonymsArms
NivolumabOPDIVOCombination Therapy

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Combination TherapyExperimentalSafety Cohort: The first 6 participants will receive Nivolumab only to start. Dose Expansion Cohort: All 26 participants will be treated with Hypofractionated Stereotactic Irradiation (HFSRT), followed by Nivolumab.
  • Nivolumab

Eligibility Criteria

        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.

          -  Demonstrate 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.

          -  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 within 72 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 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:

          -  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. Physiologic doses
             of steroid therapy (≤ 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.

          -  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.

          -  Requires escalating or chronic supraphysiologic doses of corticosteroids (> 10 mg/day
             prednisone equivalents).

          -  Has a 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.

          -  Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.

          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the pre-screening or screening visit
             through 120 days after the last dose of trial treatment.

          -  Has received 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).

          -  Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

          -  Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C Virus (HCV) (e.g.,
             HCV RNA [qualitative] is detected).

          -  Has received a live vaccine within 30 days prior to the first dose of trial
             treatment.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants with Treatment Related Adverse Events
Time Frame:Up to 24 months
Safety Issue:
Description:Safety and tolerability of nivolumab, given in combination with hypofractionated stereotactic re-irradiation of recurrent high grade gliomas.

Secondary Outcome Measures

Measure:Response Rate
Time Frame:Up to 36 months
Safety Issue:
Description:All participants will receive efficacy assessments with brain MRI at time points specified in Trial Flow Chart. Cases of suspected radiologic disease progression will be confirmed by an MRI performed approximately 8 weeks after the initial radiological assessment of progression. Immunotherapy Response Assessment in Neuro-Oncology (iRANO) and Response Assessment Criteria for High-Grade Gliomas (RANO Criteria) will be used for assessing the response to study treatment.
Measure:Overall Survival (OS) Rate at 6 Months
Time Frame:6 months
Safety Issue:
Description:OS, utilizing 95% confidence interval (95%CI).
Measure:Overall Survival (OS) Rate at 9 Months
Time Frame:9 months
Safety Issue:
Description:OS, utilizing 95% confidence interval (95%CI).

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:H. Lee Moffitt Cancer Center and Research Institute

Trial Keywords

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

Last Updated

January 23, 2017