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Trial record 8 of 1448 for:    glioblastoma

Nivolumab With Radiation Therapy and Bevacizumab for Recurrent MGMT Methylated Glioblastoma

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ClinicalTrials.gov Identifier: NCT03743662
Recruitment Status : Recruiting
First Posted : November 16, 2018
Last Update Posted : April 29, 2019
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Brief Summary:
This study is being done to see if adding nivolumab to radiation therapy and bevacizumab can increase the effectiveness of the treatment for recurrent glioblastoma.

Condition or disease Intervention/treatment Phase
Glioblastoma Radiation: Re-irradiation (RT) Drug: Bevacizumab Drug: Nivolumab Procedure: Re-resection Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 94 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Trial of the PD-1 Antibody Nivolumab in Combination With Hypofractionated Re-irradiation and Bevacizumab for Recurrent MGMT Methylated Glioblastoma
Actual Study Start Date : November 12, 2018
Estimated Primary Completion Date : November 2021
Estimated Study Completion Date : November 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Recurrent Glioblastoma, No Surgery
One cohort is for patients with recurrent GBM who are not undergoing surgical debulking as part of their treatment plan
Radiation: Re-irradiation (RT)
Re-RT will start on day 28 +/- 5 days for 5 fractions of 600cGy every other day over a 2-week period.

Drug: Bevacizumab
Bevacizumab if deemed beneficial by the investigator, will be started at the initiation of re-RT and continued for three doses in the medical arm. Patients in the surgical arm will omit the first bevacizumab dose to assure adequate wound healing after surgery and receive two doses. Bevacizumab will be dosed at 10mg/kg and given intravenously on day 28 (medical arm only), day 42 and day 56. Following day 56, further bevacizumab doses can be given every two weeks at the discretion of the treating physician.

Drug: Nivolumab

Nivolumab will be started at enrollment and each patient will receive two doses of nivolumab prior to radiation.

Nivolumab will be dosed at 3mg/kg given intravenously before re-RT (day 1 +/- 5 and 14 +/- 5) and when given with bevacizumab if deemed beneficial by the investigator, (day 28 +/- 5 (medical arm only), day 42 +/- 5, and day 56 +/-5). Nivolumab will be dosed based on body weight while combined with re-radiation and bevacizumab for safety considerations to reduce adverse events. Single agent nivolumab will be given at 240mg flat dose every 2 weeks thereafter until disease progression, withdrawal, adverse event, or death.


Experimental: Recurrent Glioblastoma, Surgery
The second cohort is for patients with recurrent GBM who are undergoing surgery as part of their treatment.
Radiation: Re-irradiation (RT)
Re-RT will start on day 28 +/- 5 days for 5 fractions of 600cGy every other day over a 2-week period.

Drug: Bevacizumab
Bevacizumab if deemed beneficial by the investigator, will be started at the initiation of re-RT and continued for three doses in the medical arm. Patients in the surgical arm will omit the first bevacizumab dose to assure adequate wound healing after surgery and receive two doses. Bevacizumab will be dosed at 10mg/kg and given intravenously on day 28 (medical arm only), day 42 and day 56. Following day 56, further bevacizumab doses can be given every two weeks at the discretion of the treating physician.

Drug: Nivolumab

Nivolumab will be started at enrollment and each patient will receive two doses of nivolumab prior to radiation.

Nivolumab will be dosed at 3mg/kg given intravenously before re-RT (day 1 +/- 5 and 14 +/- 5) and when given with bevacizumab if deemed beneficial by the investigator, (day 28 +/- 5 (medical arm only), day 42 +/- 5, and day 56 +/-5). Nivolumab will be dosed based on body weight while combined with re-radiation and bevacizumab for safety considerations to reduce adverse events. Single agent nivolumab will be given at 240mg flat dose every 2 weeks thereafter until disease progression, withdrawal, adverse event, or death.


Procedure: Re-resection
Re-resection will be performed in the surgical arm at day 14 (+/- 5 days).




Primary Outcome Measures :
  1. Overall survival [ Time Frame: 2 years ]
    in participants with recurrent glioblastoma (first recurrence)treated with re-irradiation with concurrent nivolumab (as well as bevacizumab if the investigator feels that the patient benefits from the addition) followed by adjuvant nivolumab in two parallel cohorts.


Secondary Outcome Measures :
  1. 6 month progression-free survival [ Time Frame: 6 months ]
  2. Median progression-free survival [ Time Frame: 2 years ]
  3. Objective response rate [ Time Frame: 2 years ]
    ORR using the iRANO criteria



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologic confirmed glioblastoma (WHO grade IV), IDH wildtype confirmed by DNA sequencing
  • MGMT hypermethylation in archival tumor biopsy, determined by any CLIAapproved, DNA-based assay
  • Prior maximal feasible surgical resection of biopsy
  • Prior treatment with radiation and temozolomide chemotherapy
  • Pathologic and/or Radiographic evidence of recurrent disease
  • Circumscribed enhancing tumor ≤ 5.0 cm in largest diameter (T1 post contrast)
  • 1 prior course of radiation therapy
  • Age ≥ 18 years
  • Karnofsky performance status ≥ 70%
  • Adequate bone marrow function

    • Hemoglobin ≥ 10g/dL
    • Absolute neutrophil count ≥ 1,500/mm 3
    • Absolute lymphocyte count ≥ 200/mm 3
    • Platelet count ≥ 100,000/mm3
  • Adequate liver function

    • Bilirubin <1.5 times upper limit normal (ULN)
    • AST and ALT ≤ 3 times ULN
    • Alkaline phosphatase ≤ 2 times ULN
  • Adequate renal function

    • BUN and Creatinine <1.5 times ULN

Exclusion Criteria:

  • Infratentorial location of the recurrence
  • IDH mutated glioblastoma
  • More than one prior tumor recurrence after standard first-line therapy
  • Prior radiation to the brain within ≤ 4 months
  • Circumscribed enhancing tumor >5.0 cm in largest diameter (T1 post contrast)
  • Ongoing use of anticoagulative therapy
  • Pulmonary embolus or deep vein thrombosis within preceding 2 months
  • Grade 2 or greater congestive heart failure
  • Unstable angina, myocardial infarction within past 12 months
  • Peptic ulcer, abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within past 6 months
  • Nonhealing wound, ulcer or bone fracture
  • Prior spontaneous CNS hemorrhage (as determined from clinical history, CT, or MRI)
  • Uncontrollable hypertension
  • Requiring escalating or chronic supraphysiologic doses of corticosteroids (> 4 mg dexamethasone daily) for control of disease at the time of registration
  • Previous or current treatment with an anti-CTLA-4, anti-PD-1, anti-PD-L1, or anti-PDL2 agent.
  • Previous or current treatment with bevacizumab
  • Hypersensitivity to nivolumab or bevacizumab or any of its excipients
  • Diagnosis of immunodeficiency, including Human Immunodeficiency Virus (HIV) or acquired immunodeficiency syndrome (AIDS)
  • Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  • Known history of active TB (Bacillus Tuberculosis)
  • Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
  • Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • Known history of, or any evidence of active, non-infectious pneumonitis.
  • Active infection requiring systemic therapy.
  • Pregnancy 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.
  • Unable to undergo MRI of the brain (i.e. pacemaker or any other contraindication for MRIs).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03743662


Contacts
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Contact: Christian Grommes, MD 212-610-0344 grommesc@mskcc.org
Contact: Kathryn Beal, MD 212-639-5159 bealk@mskcc.org

Locations
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United States, New Jersey
Memoral Sloan Kettering Basking Ridge Recruiting
Basking Ridge, New Jersey, United States, 07920
Contact: Christian Grommes, MD    212-639-4058      
Memorial Sloan Kettering Monmouth Recruiting
Middletown, New Jersey, United States, 07748
Contact: Christian Grommes, MD    212-639-4058      
Memorial Sloan Kettering Bergen Recruiting
Montvale, New Jersey, United States, 07645
Contact: Christian Grommes, MD    212-639-4058      
United States, New York
Memorial Sloan Kettering Commack Recruiting
Commack, New York, United States, 11725
Contact: Christian Grommes, MD    212-639-4058      
Memorial Sloan Kettering Westchester Recruiting
Harrison, New York, United States, 10604
Contact: Christian Grommes, MD    212-639-4058      
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Christian Grommes, MD    212-610-0344      
Memorial Sloan Kettering Rockville Centre Recruiting
Rockville Centre, New York, United States, 11570
Contact: Christian Grommes, MD    212-639-4058      
Memorial Sloan Kettering Nassau Recruiting
Uniondale, New York, United States, 11553
Contact: Christian Grommes, MD    212-610-0344      
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Investigators
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Principal Investigator: Christian Grommes, MD Memorial Sloan Kettering Cancer Center

Additional Information:
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Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT03743662     History of Changes
Other Study ID Numbers: 18-400
First Posted: November 16, 2018    Key Record Dates
Last Update Posted: April 29, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Memorial Sloan Kettering Cancer Center:
WHO grade IV
IDH wildtype
MGMT hypermethylation
18-400
nivolumab
recurrent glioblastoma
Memorial Sloan Kettering Cancer Center

Additional relevant MeSH terms:
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Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Bevacizumab
Nivolumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors