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Malignant GliomaPhase 1NCT02313272

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

A Phase 1 study testing Hypofractionated Stereotactic Irradiation (HFSRT), Pembrolizumab and Bevacizumab in people with Malignant Glioma, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site 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 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. 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 (HFSRT), Pembrolizumab and Bevacizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
32 participants
Where
1 siteUnited States
Study dates
28 Jul 2015to 9 Aug 2021
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 (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.
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  • 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.
  • Female participants of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving first dose of study medication. Must 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.
  • Male participants 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.

Who cannot join

  • 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.
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  • 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.
  • Prior allergic reaction to Bevacizumab.
  • History of uncontrolled hypertension, hypertensive crisis or hypertensive encephalopathy.
  • History of a non-healing wound, ulcer, or bone fracture within 90 days (3 months) prior to entry into the trial.
  • 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.
  • 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 the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, 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, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
  • Prior therapy with an anti-Programmed Death 1(PD-1), anti-Programmed Death-1 Ligand 1 (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.
  • Has received a live vaccine within 30 days prior to the first dose of trial treatment.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • H. Lee Moffitt Cancer Center and Research Institute

    Tampa, Florida, 33612

Other trials in United States

About this study

Official title: A Phase I Trial of Hypofractionated Stereotactic Irradiation (HFSRT) With Pembrolizumab and Bevacizumab in Patients With Recurrent High Grade Gliomas

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.

Being tested
Hypofractionated Stereotactic Irradiation (HFSRT), Pembrolizumab, Bevacizumab
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
Medical subject headings
Glioma, Neoplasms, Neurologic Manifestations

What participants receive

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

  • Hypofractionated Stereotactic Irradiation (HFSRT)Radiation

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

  • PembrolizumabDrug

    Also called Keytruda®, MK-3475

    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.

  • BevacizumabDrug

    Also called Avastin®

    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.

Study groups in NCT02313272
Study groupRoleWhat they receive
HFSRT with Pembrolizumab and BevacizumabExperimentalHypofractionated Stereotactic Irradiation (HFSRT). Pembrolizumab intravenous (IV) infusion every 3 weeks. Bevacizumab administered intravenously every 2 weeks.
Receives: Radiation: Hypofractionated Stereotactic Irradiation (HFSRT); Drug: Pembrolizumab; Drug: Bevacizumab

What is being measured

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

  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).

    Measured: Up to 24 months

Secondary outcomes (1)

  1. Response Rate (RR)

    Response rate of pembrolizumab given in combination with bevacizumab and hypofractionated stereotactic re-irradiation of recurrent high grade gliomas. Response to treatment will be assessed by the investigator and according to the Response Assessment Criteria for High-Grade Gliomas (RANO Criteria). Brain MRI will be performed every 6 weeks beginning at the end of Week 6 (± 1 week) for 3 cycles and then every 12 weeks (± 1 week) until disease progression or treatment discontinuation, whichever occurs later.

    Measured: Up to 24 months

Timeline

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

  1. First posted10 Dec 2014 (estimated)
  2. Study start28 Jul 2015
  3. Primary completion13 Sep 2018
  4. Study completion9 Aug 2021

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
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02313272
Sponsor's protocol ID
MCC-17978
Status last verified
Dec 2022
First submitted
5 Dec 2014
Last updated
23 Oct 2023
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 34642366

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Hypofractionated Stereotactic Irradiation (HFSRT), Pembrolizumab and Bevacizumab in people with Malignant Glioma, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site 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 17 inclusion and 28 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 23 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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?

Yes. Results are posted in the registry (first posted 23 Oct 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Maximum Tolerated Dose (MTD) (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 NCT02313272, which also lists 1 linked publication.

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 23 Oct 2023.

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