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Malignant GliomaPhase 1NCT02829931

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

A Phase 1 study testing Hypofractionated Stereotactic Irradiation, Nivolumab and Bevacizumab in people with Malignant Glioma, run by H. Lee Moffitt Cancer Center and Research Institute at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Malignant Glioma
What is being tested?
Hypofractionated Stereotactic Irradiation, Nivolumab and Bevacizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
33 participants
Where
2 sitesUnited States
Study dates
22 Aug 2016to 22 Nov 2022
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.
  • Males should agree to use an adequate method of contraception starting with the first dose of study therapy through 7 months after the last dose of study therapy.

Who cannot join

  • 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.
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  • 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.
  • Requires escalating or chronic supraphysiologic doses of corticosteroids (>2 mg dexamethasone or > 10 mg/day prednisone equivalents) at the start day of treatment.
  • 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 prior history of uncontrolled hypertension, hypertensive crisis or hypertensive encephalopathy.
  • Has history of non-healing wound, ulcer, or bone fracture within 90 days (3 months) prior to entry into the trial.
  • Has history of gastrointestinal bleeding or any other hemorrhage/bleeding event ≥ grade 3 (CTCAE, v. 4) within 30 days prior to entry in to the trial.
  • 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-angiogenic agent such as bevacizumab, 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.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • H. Lee Moffitt Cancer Center and Research Institute

    Tampa, Florida, 33612

Other trials in United States

About this study

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

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.

Being tested
Hypofractionated Stereotactic Irradiation, Nivolumab, Bevacizumab, Ipilimumab
Keywords
recurrent glioma, high grade glioma, head and neck disease, grade III glioma, grade IV glioma, radiation therapy
Medical subject headings
Glioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Hypofractionated Stereotactic IrradiationRadiation

    Also called HFSRT, radiation therapy

    Hypofractionated Stereotactic Irradiation (HFSRT) prior to nivolumab.

  • NivolumabDrug

    Also called OPDIVO

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

  • BevacizumabDrug

    Also called Avastin

    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.

  • IpilimumabDrug

    Also called Yervoy

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

Study groups in NCT02829931
Study groupRoleWhat they receive
Combination TherapyExperimentalSafety 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
Receives: Radiation: Hypofractionated Stereotactic Irradiation; Drug: Nivolumab; Drug: Bevacizumab; Drug: Ipilimumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to 24 months

Secondary outcomes (3)

  1. Response Rate

    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.

    Measured: Up to 36 months

  2. Overall Survival (OS) Rate at 6 Months

    OS, utilizing 95% confidence interval (95%CI).

    Measured: 6 months

  3. Overall Survival (OS) Rate at 9 Months

    OS, utilizing 95% confidence interval (95%CI).

    Measured: 9 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jul 2016 (estimated)
  2. Study start22 Aug 2016
  3. Primary completion11 Aug 2021
  4. Study completion22 Nov 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
33 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02829931
Sponsor's protocol ID
MCC-18661
Status last verified
Jan 2023
First submitted
8 Jul 2016
Last updated
19 Jan 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Hypofractionated Stereotactic Irradiation, Nivolumab and Bevacizumab in people with Malignant Glioma, run by H. Lee Moffitt Cancer Center and Research Institute at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants with Treatment Related Adverse Events (time frame: Up to 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02829931.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jan 2023.

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