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Trial record 2 of 1110 for:    Recruiting, Not yet recruiting, Active, not recruiting, Completed, Enrolling by invitation, Approved for marketing Studies | glioblastoma

Pembrolizumab and Reirradiation in Bevacizumab Naïve and Bevacizumab Resistant Recurrent Glioblastoma

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ClinicalTrials.gov Identifier: NCT03661723
Recruitment Status : Recruiting
First Posted : September 7, 2018
Last Update Posted : June 18, 2019
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
David Reardon, MD, Dana-Farber Cancer Institute

Brief Summary:

This research study is studying pembrolizumab and re-irradiation as possible treatments for glioblastoma.

The drugs involved in this study are:

  • Pembrolizumab
  • Radiation
  • Bevacizumab, an FDA-approved drug for treating recurrent glioblastoma multiforme (GBM)

Condition or disease Intervention/treatment Phase
Glioblastoma Drug: Pembrolizumab Drug: Bevacizumab Radiation: Re-irradiation Phase 2

Detailed Description:

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.

How the Study Interventions work:

Pembrolizumab: Pembrolizumab has been studied in lab experiments and in other types of cancer, and information from these studies suggests that it may be beneficial in this type of cancer. Pembrolizumab is a drug (an antibody) that may treat cancer by working with the immune system.

The FDA (the U.S. Food and Drug Administration) has not approved pembrolizumab for this specific disease but it has been approved for other uses.

Radiation (Re-irradiation): Radiotherapy destroys cancer cells using radiation aimed at a cancer from a machine.

The FDA (the U.S. Food and Drug Administration) has approved re-irradiation as a treatment option for this disease.

Bevacizumab: Bevacizumab (also known as "Avastin") is designed to prevent or slow down the growth of cancer cells by blocking the growth of blood vessels.

The FDA (the U.S. Food and Drug Administration) has approved bevacizumab as a treatment option for this disease.

In this research study, the investigators are looking to determine if this combination (pembrolizumab + re-irradiation) proves helpful in treating this cancer. If the participant has already been receiving bevacizumab, the participant will continue to receive this along with pembrolizumab and re-irradiation. By doing this, the investigators will look to determine if this combination (pembrolizumab and bevacizumab + re-irradiation) proves helpful in treating this cancer.

This study will also test the safety and tolerability of this combination (pembrolizumab + re-irradiation) when given alone or with bevacizumab


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial of Pembrolizumab and Reirradiation in Bevacizumab Naïve and Bevacizumab Resistant Recurrent Glioblastoma
Actual Study Start Date : September 28, 2018
Estimated Primary Completion Date : August 31, 2020
Estimated Study Completion Date : February 28, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Pembrolizumab + Radiation (lead-in)
  • Pembrolizumab (200 mg) will initially be administered intravenously (IV) once every 3 weeks. (De-escalation dosing frequencies = once every 4 weeks and once every 6 weeks.)
  • Re-irradiation (35 Gy) will be administered to patients 5 days per week for 2 weeks
Drug: Pembrolizumab
Pembrolizumab is a drug (an antibody) that may treat cancer by working with the immune system
Other Name: Keytruda

Radiation: Re-irradiation
Radiotherapy destroys cancer cells using radiation aimed at a cancer from a machine

Experimental: Pembrolizumab + Bevacizumab + Radiation (lead-in)
  • Pembrolizumab (200 mg) will initially be administered intravenously (IV) once every 3 weeks. (De-escalation dosing frequencies = once every 4 weeks and once every 6 weeks.)
  • Bevacizumab (15 mg/kg) will be administered intravenously (IV) once every 3 weeks
  • Re-irradiation (35 Gy) will be administered to patients 5 days per week for 2 weeks
Drug: Pembrolizumab
Pembrolizumab is a drug (an antibody) that may treat cancer by working with the immune system
Other Name: Keytruda

Drug: Bevacizumab
Bevacizumab (also known as "Avastin") is designed to prevent or slow down the growth of cancer cells by blocking the growth of blood vessels.
Other Name: Avastin

Radiation: Re-irradiation
Radiotherapy destroys cancer cells using radiation aimed at a cancer from a machine

Experimental: Pembrolizumab + Radiation
  • Pembrolizumab (200 mg) will initially be administered intravenously (IV) once every 3 weeks
  • Re-irradiation (35 Gy) will be administered to patients 5 days per week for 2 weeks
Drug: Pembrolizumab
Pembrolizumab is a drug (an antibody) that may treat cancer by working with the immune system
Other Name: Keytruda

Radiation: Re-irradiation
Radiotherapy destroys cancer cells using radiation aimed at a cancer from a machine

Experimental: Pembrolizumab + Bevacizumab + Radiation
  • Pembrolizumab (200 mg) will initially be administered intravenously (IV) once every 3 weeks
  • Bevacizumab (15 mg/kg) will be administered intravenously (IV) once every 3 weeks
  • Re-irradiation (35 Gy) will be administered to patients 5 days per week for 2 weeks
Drug: Pembrolizumab
Pembrolizumab is a drug (an antibody) that may treat cancer by working with the immune system
Other Name: Keytruda

Drug: Bevacizumab
Bevacizumab (also known as "Avastin") is designed to prevent or slow down the growth of cancer cells by blocking the growth of blood vessels.
Other Name: Avastin

Radiation: Re-irradiation
Radiotherapy destroys cancer cells using radiation aimed at a cancer from a machine




Primary Outcome Measures :
  1. Objective response rate [ Time Frame: 2 years ]
  2. Overall survival rate [ Time Frame: 12 months ]

Secondary Outcome Measures :
  1. Progression free survival [ Time Frame: 6 months ]
  2. Duration of response [ Time Frame: 4 weeks ]
  3. Safety & Tolerability: toxicities and grades experienced by participants [ Time Frame: 2 years ]
    Safety will be assessed by quantifying the toxicities and grades experienced by participants who have received Pembrolizumab, including serious adverse events (SAEs), other Reportable Adverse Events, and events of clinical interest



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:

1.1 Histologically confirmed World Health Organization (WHO) Grade IV glioblastoma. Patients with original histology of low-grade glioma and subsequent histological diagnosis of GBM are eligible. Other WHO grade IV glial neoplasms such as gliosarcoma are NOT eligible 1.2 Willing and able to provide written informed consent/assent for the trial 1.3 ≥ 18 years of age on day of signing informed consent 1.4 Karnofsky performance status (KPS) ≥ 70 (Appendix A) 1.5 Unequivocal evidence for tumor progression by MRI scan 1.6 MRI within 14 days prior to start of study drug (with vascular imaging when possible). Corticosteroid dose must be stable or decreasing for at least 5 days prior to the scan. If steroids are added or the steroid dose is increased between the date of the screening MRI scan and Day 1 dose, a new baseline scan is required 1.7 Measurable disease as per Response Assessment in Neuro-Oncology (RANO) criteria 1.8 Cohort A patients must be at their first or second relapse; Cohort B patients must have progressed on no more than one prior bevacizumab-containing regimen (may have received any # of non-bevacizumab-containing regimens). Patients who were treated with prior bevacizumab but did not progress or experienced significant toxicity, are not eligible 1.9 Previous first line therapy with at least radiotherapy utilizing standard dosing of CNS radiation including 60 Gy in 30 fractions, 59.4 Gy in 1.8 Gy per fraction or equivalent 1.10 The following time periods must have elapsed from projected Day 1 dose:

  1. At least 3 weeks from prior surgical resection
  2. At least 1 week from stereotactic biopsy
  3. At least 6 months from completion of prior radiotherapy (patient may still be eligible if s/he has a new area of enhancement outside the 80% isodose line of the original radiation field)
  4. At least 4 weeks from cytotoxic therapy (at least 23 days for temozolomide, and at least 6 weeks from nitrosoureas)
  5. At least 1 week from cancer vaccines
  6. At least 6 weeks from antibodies
  7. At least 4 weeks (or 5 half-lives, whichever is shorter) from any investigational agent, daily administered chemotherapeutics, or another anti-tumor therapies and 1 week for cancer vaccines
  8. Cohort B patients only: Day 1 of bevacizumab on-study must be at least 3 weeks from last dose of prior course of Avastin/bevacizumab.

1.11 All clinically significant toxic effects of prior therapy must have recovered to grade 0 or 1 or pre-treatment baseline (excluding alopecia, laboratory values listed per inclusion criteria, and lymphopenia) 1.12 Adequate organ function as defined below (screening labs performed within 14 days of treatment initiation): 1.12.1 Hematologic: Absolute neutrophil count (ANC) ≥1,500 /uL; Platelets ≥100,000 / uL; Hemoglobin ≥9 g/dL or ≥5.6 mmol/L 1.12.2 Renal: Serum creatinine ≤1.5 X institutional upper limit of normal (ULN) OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≥60 mL/min for participant with creatinine levels > 1.5 X institutional ULN 1.12.3 Hepatic Serum total bilirubin ≤ 1.5 X institutional ULN OR Direct bilirubin ≤ institutional ULN for participants with total bilirubin levels > 1.5 X institutional ULN; aspartate aminotransferase (AST; SGOT) and alanine aminotransferase (ALT; SGPT) ≤ 2.5 X institutional ULN (OR ≤ 5 X institutional ULN for participants with Gilberts syndrome) 1.12.4 Coagulation: International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT) ≤1.5 X institutional ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants 1.12.5 Pulmonary: Resting baseline oxygen saturation by pulse oximetry ≥92% at rest

1.13 Negative urine or serum pregnancy within 72 hours prior to registration from any woman of child-bearing potential (WOCBP), defined as any woman physiologically capable of becoming pregnant. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

1.14 WOCBP (defined above) must agree to use a highly effective method of contraception (detailed in protocol eligibility) consistently and correctly as described below during study treatment and for 120 days after study discontinuation.

1.15 Male participants must agree to use at least one of the methods of contraception detailed in protocol eligibility starting with the first dose of study therapy through 120 days after the last dose of therapy.

EXCLUSION CRITERIA:

2.1 Recurrent tumor greater than 6 cm in maximum diameter 2.2 Currently participating or plans to participate in another study of an investigational agent or using an investigational device.

2.3 Tumor primarily localized to the brainstem or spinal cord. 2.4 Presence of multifocal tumor, diffuse leptomeningeal or extracranial disease.

Medical History/Conditions/Concomitant Medical Illnesses:

2.5 Diagnosis of immunodeficiency. 2.6 History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator. e.g. unstable angina pectoris, cardiac arrhythmia or psychiatric illness/social situations that would limit compliance with study requirements.

2.7 History of known coagulopathy that increases risk of bleeding or a history of clinically significant hemorrhage within 12 months of start of study drug.

2.8 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.

2.9 Gastrointestinal bleeding or any other hemorrhage/bleeding event CTCAE Grade > 3 within 6 months of start of study drug.

2.10 Known additional malignancy that is progressing or requires active treatment within 1 year of start of study drug, except for those treated with surgical therapy only (e.g. basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy).

2.11 Active autoimmune disease requiring systemic treatment in the past 2 years (e.g. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg thyroxine, insulin, or physiologic corticosteroid replacement for adrenal insufficiency or pituitary/hypothalamic dysfunction, etc.) is not considered a form of systemic treatment.

2.12 History of (non-infectious) pneumonitis that required steroids or has current pneumonitis.

2.13 Active infection requiring systemic therapy. 2.14 Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

2.15 Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies) and is receiving antiretroviral therapy.

2.16 Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C [e.g., hepatitis C virus (HCV) RNA (qualitative) is detected].

2.17 History of non-healing wounds or ulcers, or bone refractures within 3 months of fracture.

2.18 History of arterial thromboembolism within 12 months of start of study drug.

2.19 Clinically significant cardiovascular disease within 12 months of start of study drug, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication, percutaneous transluminal coronary angioplasty/stent.

2.20 Known history of active Bacillus Tuberculosis (TB) 2.21 Known hypersensitivity to any of the study therapy products and/or any of their excipients.

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

Prior Therapy:

2.23 Has received prior interstitial brachytherapy, implanted chemotherapy, stereotactic radiosurgery or therapeutics delivered by local injection or convection enhanced delivery (this exclusion applies to any locally administered therapy, including intratumoral vaccines).

2.24 Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 or with an agent directed to another stimulatory or co-stimulatory T-cell receptor (eg CTLA-4, OX-40, CD137). (These therapies target checkpoint proteins on immune cells called T-Cells.PD-1 = Programmed cell death protein 1. CTLA-4 = cytotoxic T-lymphocyte-associated protein 4. OX-40 - AKA CD134 & TNFRSF4 = Tumor necrosis factor receptor superfamily, member 4) 2.25 Has received prior Vascular endothelial growth factor (VEGF) or VEGFR inhibitor therapy such as bevacizumab, cediranib, aflibercept, vandetanib, XL-184 (Cabozantinib), sunitinib, etc. (Cohort A only)

Other Meds:

2.26 Is receiving any form of immunosuppressive therapy (e.g. chronic systemic steroid therapy exceeding dosage of 10 mg daily of prednisone equivalent) within 7 days prior to the first dose of study drug.

2.27 Has received systemic immunosuppressive treatments (aside from systemic corticosteroids as described in protocol) within six months of start of study drug (such as methotrexate, chloroquine, azathioprine, etc).

2.28 Requires treatment with high dose systemic corticosteroids defined as dexamethasone > 2 mg/day or bioequivalent for at least 3 consecutive days within 2 weeks of start of study drug.

  • Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
  • Participants are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption).
  • Physiologic replacement doses of systemic corticosteroids are permitted, even if > 10 mg/day prednisone equivalents.
  • A brief course of corticosteroids for prophylaxis or for treatment of non-autoimmune conditions is permitted.

2.29 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. (Therapeutic or prophylactic therapy with low-molecular weight heparin is allowed.) 2.30 Has received a live vaccine within 30 days prior to the first dose of study drug.


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): NCT03661723


Contacts
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Contact: David A Reardon, MD 617-632-4750 david_reardon@dfci.harvard.edu

Locations
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United States, Massachusetts
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02115
Contact: Eric Wong, MD       ewong@bidmc.harvard.edu   
Principal Investigator: Eric Wong, MD         
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: David A Reardon, MD    647-632-4750    david_reardon@dfci.harvard.edu   
Principal Investigator: David A Reardon, MD         
Massachusetts General Hospital Not yet recruiting
Boston, Massachusetts, United States, 02214
Contact: Justin Jordan, MD       JTJORDAN@mgh.harvard.edu   
Principal Investigator: Justin Jordan, MD         
United States, New York
Columbia University / Herbert Irving Comprehensive Cancer Center Recruiting
New York, New York, United States, 10032
Contact: Fabio M Iwamoto, MD    212-342-0571    fi2146@cumc.columbia.edu   
Principal Investigator: Fabio M Iwamoto, MD         
United States, Pennsylvania
Hospital of the University of Pennsylvania, Abramson Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Arati S Desai, MD, MAS    212-615-5858    Arati.Desai@uphs.upenn.edu   
Principal Investigator: Arati S Desai, MD         
Sponsors and Collaborators
Dana-Farber Cancer Institute
Merck Sharp & Dohme Corp.
Investigators
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Principal Investigator: David A Reardon, MD Dana-Farber Cancer Institute

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Responsible Party: David Reardon, MD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT03661723     History of Changes
Other Study ID Numbers: 18-277
3475-787 ( Other Identifier: Merck )
First Posted: September 7, 2018    Key Record Dates
Last Update Posted: June 18, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by David Reardon, MD, Dana-Farber Cancer Institute:
Glioblastoma
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
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors