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Pembrolizumab +/- Bevacizumab for Recurrent GBM

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ClinicalTrials.gov Identifier: NCT02337491
Recruitment Status : Active, not recruiting
First Posted : January 13, 2015
Last Update Posted : August 31, 2016
Sponsor:
Information provided by (Responsible Party):

Study Description
Brief Summary:
In this research study, the investigators are looking to determine the effectiveness of Pembrolizumab (MK-3475) when given with bevacizumab or when given alone for the treatment of recurrent glioblastoma multiforme (GBM). This study will also test the safety and tolerability of Pembrolizumab (MK-3475) when given alone or with bevacizumab.

Condition or disease Intervention/treatment Phase
Glioblastoma Drug: Pembrolizumab Drug: Bevacizumab Phase 2

Detailed Description:

Pembrolizumab (MK-3475) is a humanized monoclonal antibody. An antibody is a common type of protein made in the body in response to a foreign substance. Antibodies attack foreign substances and protect against infection. Antibodies can also be produced in the laboratory for use in treating patients, an antibody that is made in the lab is also known as a humanized monoclonal antibody. There are now several approved antibodies for the therapy of cancer and other disease. Pembrolizumab (MK-3475) has been studied in lab experiments and in other types of cancer. Information from these studies suggests that Pembrolizumab (MK-3475) may be beneficial in your type of cancer.

Bevacizumab, also known as Avastin, is approved by the FDA for treating recurrent GBM. Bevacizumab is an anti-angiogenic medicine, which means it blocks blood vessels from forming that could supply the tumor with nutrients and oxygen.

If you participate in this study, you will then be "randomized" into one of two study groups; Cohort A or Cohort B. Randomization means that you are put into a group by chance. It is like flipping a coin. Neither you nor the research doctor will choose what group you will be in. You have an approximately 60% chance of being placed in to Cohort A and an approximately 40% chance of being placed into Cohort B. Study Groups:

  • Cohort A: study drug, Pembrolizumab (MK-3475) + bevacizumab
  • Cohort B: Study drug, Pembrolizumab (MK-3475)

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 82 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Pembrolizumab (MK-3475) With and Without Bevacizumab for Recurrent Glioblastoma
Study Start Date : February 2015
Primary Completion Date : August 2016

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Active Comparator: Cohort A
Pembrolizumab and Bevacizumab
Drug: Pembrolizumab
Administered intravenously
Other Names:
  • MK-3475
  • SCH 900475
Drug: Bevacizumab
Administered Intravenously
Other Name: Avastin
Active Comparator: Cohort B
Pembrolizumab
Drug: Pembrolizumab
Administered intravenously
Other Names:
  • MK-3475
  • SCH 900475


Outcome Measures

Primary Outcome Measures :
  1. 6-month Progression Free Survival [ Time Frame: 6 months ]
    To evaluate the anti-tumor activity of pembrolizumab among subjects with bevacizumab-naïve recurrent glioblastoma when treated with pembrolizumab plus bevacizumab (Cohort A), and when treated with pembrolizumab monotherapy (Cohort B) as assessed by the 6-month progression-free survival (PFS-6) rate.

  2. Cohort A Recommended Phase II Dose/MTD [ Time Frame: 6 months ]
    To determine the RP2D/MTD of pembrolizumab when administered with bevacizumab (Cohort A) among recurrent glioblastoma patients


Secondary Outcome Measures :
  1. Safety and tolerability of Pembrolizumab (Assesed by reported adverse events using CTCAE version 4.0) [ Time Frame: 1 year ]
    Assesed by reported adverse events using CTCAE version 4.0

  2. Progression Free Survival [ Time Frame: 2 years ]
    To evaluate the progression-free survival (PFS) of subjects with bevacizumab-naive, recurrent glioblastoma when administered pembrolizumab with and without bevacizumab among.

  3. Overall Survival [ Time Frame: 2 years ]
    To evaluate the overall survival (OS) of subjects with bevacizumab naive, recurrent glioblastoma when administered pembrolizumab with and without bevacizumab.

  4. Overall Radiographic Response [ Time Frame: 2 years ]
    To evaluate the overall radiographic response (ORR) rate and duration among subjects with bevacizumab-naive, recurrent glioblastoma when administered pembrolizumab with and without bevacizumab.


Eligibility Criteria

Information from the National Library of Medicine

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

Inclusion Criteria:

  • Have histologically confirmed World Health Organization Grade IV malignant glioma (glioblastoma or gliosarcoma). Participants will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of glioblastoma or variants is made.
  • Previous first line therapy with at least radiotherapy and temozolomide
  • Be at first or second relapse.
  • Participants must have shown unequivocal evidence for tumor progression by MRI or CT scan.
  • CT or MRI within 14 days prior to start of study drug.
  • An interval of at least 4 weeks (to start of study agent) between prior surgical resection or one week for stereotactic biopsy.
  • An interval of at least 12 weeks from the completion of radiation therapy to start of study drug unless there is a new area of enhancement consistent with recurrent tumor outside the radiation field or there is unequivocal histologic confirmation of tumor progression
  • Participants must have recovered to grade 0 or 1 or pre-treatment baseline from clinically significant toxic effects of prior therapy (including but not limited to exceptions of alopecia, laboratory values listed per inclusion criteria, and lymphopenia which is common after therapy with temozolomide).
  • From the projected start of scheduled study treatment, the following time periods must have elapsed: 5 half-lives from any investigational agent, 4 weeks from cytotoxic therapy (except 23 days for temozolomide and 6 weeks from nitrosoureas), 6 weeks from antibodies, or 4 weeks (or 5 half-lives, whichever is shorter) from other anti-tumor therapies.

Exclusion Criteria:

  • Current or planned participation in a study of an investigational agent or using an investigational device.
  • Has a diagnosis of immunodeficiency.
  • Has tumor primarily localized to the brainstem or spinal cord.
  • Has presence of diffuse leptomeningeal disease or extracranial disease.
  • Has received systemic immunosuppressive treatments within 6 months of start of study drug
  • Requires treatment with high dose systemic corticosteroids defined as dexamethasone > 4 mg/day or bioequivalent for at least 3 consecutive days within 2 weeks of start of study drug.
  • Has received prior interstitial brachytherapy, implanted chemotherapy, stereotactic radiosurgery or therapeutics delivered by local injection or convection enhanced delivery.
  • Requires therapeutic anticoagulation with warfarin at baseline; patients must be off warfarin or warfarin-derivative anti-coagulants for at least 7 days prior to starting study drug; however, therapeutic or prophylactic therapy with low-molecular weight heparin is allowed.
  • Has history of known coagulopathy that increases risk of bleeding or a history of clinically significant hemorrhage within 12 months of start of study drug
  • Has evidence of intratumoral or peritumoral hemorrhage on baseline MRI scan other than those that are grade ≤ 1 and either post-operative or stable on at least 2 consecutive MRI scans.
  • Has gastrointestinal bleeding or any other hemorrhage/bleeding event CTCAE Grade > 3 within 6 months of start of study drug.
  • Has a known additional malignancy that is progressing or requires active treatment within 3 years of start of study drug. 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.
  • Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
  • Has an active infection requiring systemic therapy.
  • Has a 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.
  • 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 within the projected duration of the trial
  • Has a known history of HIV
  • Has known active Hepatitis B or Hepatitis C
  • Has received a live vaccine within 30 days prior to the first dose of study drug.
  • Has a known hypersensitivity to any of the study therapy products.
  • Has received anti-angiogenic or anti-VEGF targeted agents (e.g. bevacizumab, cediranib, aflibercept, vandetanib, XL-184, sunitinib, etc)
  • Has a history of non-healing wounds or ulcers, or bone refractures within 3 months of fracture
  • Has a history of arterial thromboembolism within 12 months of start of study drug.
  • Has inadequately controlled hypertension
  • Has a history of hypertensive crisis or hypertensive encephalopathy
  • Has had clinically significant cardiovascular disease within 12 months of start of study drug
  • Has a history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to start of study drug.
Contacts and Locations

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): NCT02337491


Locations
United States, California
University of California, Los Angeles
Los Angeles, California, United States, 90095
University of California, San Francisco
San Francisco, California, United States, 94143-0372
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02113
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, New York
Memorial Sloan-Kettering Cancer
New York City, New York, United States, 10021
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Texas
UT, MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Utah
Huntsman Cancer Institute
Salt Lake City, Utah, United States, 84112
Sponsors and Collaborators
Dana-Farber Cancer Institute
Investigators
Principal Investigator: David Reardon, MD Dana-Farber Cancer Institute
More Information

Responsible Party: David Reardon, MD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT02337491     History of Changes
Other Study ID Numbers: 14-477
First Posted: January 13, 2015    Key Record Dates
Last Update Posted: August 31, 2016
Last Verified: August 2016

Keywords provided by David Reardon, MD, Dana-Farber Cancer Institute:
Recurrent

Additional relevant MeSH terms:
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
Pembrolizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents