Tremelimumab and Durvalumab in Combination or Alone in Treating Patients With Recurrent Malignant Glioma
A Phase II, Open Label, Clinical Trial Of Pre-Surgical and Adjuvant Treatment of Recurrent Malignant Glioma With Tremelimumab and Durvalumab (MEDI4736) Alone and in Combination to Determine Immunologic Changes From Treatment
4 other identifiers
interventional
36
1 country
1
Brief Summary
The main purpose of this trial is to investigate the effects of a new class of drugs that help the patient's immune system attack their tumor (glioblastoma multiforme - GBM). These drugs have already shown benefit in some other cancer types and are now being explored in GBM. Both tremelimumab and durvalumab (MEDI4736) are "investigational" drugs, which means that the drugs are not approved by the Food and Drug Administration (FDA). Both drugs are antibodies (proteins used by the immune system to fight infections and cancers). Durvalumab attaches to a protein in tumors called PD-L1. It may prevent cancer growth by helping certain blood cells of the immune system get rid of the tumor. Tremelimumab stimulates (wakes up) the immune system to attack the tumor by inhibiting a protein molecule called CTLA-4 on immune cells. Combining the actions of these drugs may result in better treatment options for patients with glioblastoma.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Nov 2016
Typical duration for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 27, 2016
CompletedFirst Posted
Study publicly available on registry
June 9, 2016
CompletedStudy Start
First participant enrolled
November 1, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 9, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
June 17, 2020
CompletedResults Posted
Study results publicly available
April 18, 2022
CompletedApril 18, 2022
March 1, 2022
1.5 years
May 27, 2016
October 25, 2021
March 17, 2022
Conditions
Outcome Measures
Primary Outcomes (1)
T-cell (Immunologic) Changes in Blood
To determine the T-cell changes that occur in glioblastoma treated with tremelimumab and MEDI4736 as single agents and in combination. The changes from baseline will be assessed in blood samples and tissue samples before pre-surgery treatment with MEDI4736 and/or tremelimumab, day of surgery, and during adjuvant treatment, for all patients in the 3 arms.
From baseline up to end of treatment, where all patients received at least 1 dose pre-surgery, and range of cycles attempted post-surgery was 0-16 (1 Cycle = 4 weeks)
Secondary Outcomes (4)
MRI Changes
Baseline and 3 days after surgery
Number of Patients Adverse Events Regardless of Attribution to the Study Drug Graded 3, 4, and 5
From baseline, pre-surgery treatment period (2 weeks prior to surgery), and post-surgery treatement, where the range of cycles attempted post-surgery was 0-16 (1 Cycle = 4 weeks), to 90 days post treatment discontinuation
Overall Survival
From the start of treatment (pre-surgery treatment period = 2 weeks), to surgery, to post-surgery treatment, where range of cycles attempted was 0-16 (1 Cycle = 4 weeks), to 2 years post treatment discontinuation
Time to Progression
From start of treatment (pre-surgery treatment period = 2 weeks), to surgery, to post-surgery treatment where range of cycles attempted was 0-16 (1 Cycle = 4 weeks), and up to 2 years of follow-up after treatment discontinuation
Other Outcomes (2)
T-cell Changes
Up to 2 years
PDL1 Expression
Up to 2 years
Study Arms (3)
Treatment (durvalumab)
ACTIVE COMPARATORPatients receive durvalumab IV over 1 hour on days 1 and 15. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity.
Treatment (tremelimumab and durvalumab)
ACTIVE COMPARATORPatients receive tremelimumab IV over 1 hour on day 1 then durvalumab IV over 1 hour on days 1 and 15. Courses repeat every 4 weeks for up to 7 courses. Patients then receive both tremelimumab and durvalumab IV over 1 hour every 12 weeks in the absence of disease progression or unacceptable toxicity.
Treatment (tremelimumab)
EXPERIMENTALPatients receive tremelimumab IV over 1 hour on day 1. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Interventions
Given IV
Correlative Studies
Undergo surgical tumor resection
Given IV
Eligibility Criteria
You may qualify if:
- Patients must have a grade III or IV glioma that has progressed after standard radiotherapy (RT) and temozolomide (TMZ) (Note: Pathology will need to be reviewed locally but registration can occur based on pathology report)
- Patients must have had radiographic evidence of tumor progression by brain MRI or computed tomography (CT) scan with contrast
- Patients must be \> 12 weeks from completion of radiation therapy unless there is tissue confirmation of tumor recurrence or there is progression outside the radiation treatment field
- Prior therapy with gamma knife or other focal high-dose radiotherapy is allowed, but the patient must have subsequent histologic documentation of recurrence, unless the recurrence occurs remote from the treated site
- Patients must be surgical candidates
- Patients must have had no more than 3 prior lines of chemotherapy; this includes the initial treatment and two relapses; concurrent and adjuvant TMZ-based chemotherapy, including the combination of TMZ with another agent, is considered one line of chemotherapy; for clarification, please contact the principle investigator (PI), Dr. Jeffrey Raizer, at (312) 695-0990
- Patients must be \>=
- weeks from TMZ
- weeks from a nitrosoureas
- weeks from a biologic or targeted agent (i.e. small molecule)
- weeks for a vascular endothelial growth factor (VEGF) inhibitor (i.e. bevacizumab)
- Patients must exhibit a Karnofsky performance status (KPS) \>= 70
- Life expectancy of \>= 12 weeks (per treating investigator's discretion)
- Patients must be on a stable or decreasing dose of corticosteroids within 5 days prior to CT scan or MRI (which is done to determine eligibility); the goal should be dexamethasone 4 mg or less at the time of starting treatment; if patient requires \> 4mg of steroid, please check with the principle investigator (PI); requirement for greater than 10mg of steroid will make the patient ineligible
- Leukocytes \>= 3,000/mcL
- +20 more criteria
You may not qualify if:
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site); previous enrolment or randomization in the present study
- Has received prior therapy with an anti-programmed cell death protein 1 (PD-1), anti-programmed cell death ligand 2 (PD-L2), anti-cluster of differentiation (CD)137, 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 known active hepatitis B (e.g., hepatitis B virus antigen \[HBsAg\] reactive) or hepatitis C (e.g., hepatitis c virus \[HCV\] ribonucleic acid \[RNA\] \[qualitative\] is detected)
- Known active human immunodeficiency virus (HIV1/2 antibodies)
- Patient has history of primary immunodeficiency OR has received any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment, excluding intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses; attempts should be made to have patient on lowest possible dose of steroids (acceptable range 4-10mg, please contact PI if dose is \>4 mg) and weaned to off as is feasible
- Patients receiving any other investigational chemotherapeutic agents within 30 days prior to the first dose of trial treatment
- Mean QT interval corrected for heart rate (QTc) \>= 470 ms calculated from an electrocardiograms (ECGs) using Bazett's Correction; if first ECG is abnormal, then the mean will be calculated from 3 consecutive ECGs (taken 2-5 minutes apart); please contact the PI for further clarification
- Active or prior documented history of immunologic disorder including autoimmune disease within the past 2 years NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded
- Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
- History of allogeneic organ transplant
- Uncontrolled intercurrent illness including, but not limited to,
- Ongoing or active infection,
- Symptomatic congestive heart failure,
- Uncontrolled hypertension (defined as \> 150/90)
- Unstable angina pectoris,
- +11 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Northwestern Universitylead
- AstraZenecacollaborator
- MedImmune LLCcollaborator
- National Cancer Institute (NCI)collaborator
Study Sites (1)
Northwestern University
Chicago, Illinois, 60611, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Karan Dixit, MD
- Organization
- Northwestern University, Feinberg School of Medicine
Study Officials
- PRINCIPAL INVESTIGATOR
Jeffrey Raizer, MD
Northwestern University
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 27, 2016
First Posted
June 9, 2016
Study Start
November 1, 2016
Primary Completion
May 9, 2018
Study Completion
June 17, 2020
Last Updated
April 18, 2022
Results First Posted
April 18, 2022
Record last verified: 2022-03