Skip to main content
Clinical Trials/NCT02336165
NCT02336165CompletedPhase 2

Phase 2 Study to Evaluate the Clinical Efficacy and Safety of MEDI4736 in Patients With Glioblastoma (GBM)

Ludwig Institute for Cancer Research1 site in 1 country159 target enrollmentStarted: February 26, 2015Last updated:
Conditions
Interventions
Drugs

Trial Snapshot

Phase
Phase 2
Status
Completed
Enrollment
159
Locations
1
Primary Endpoint
Overall Survival Rate at 12 Months (OS-12) as Estimated Using the Kaplan-Meier Method (Cohort A)

Study Overview

Brief Summary

This is an ongoing Phase 2, open-label, multicenter, non-randomized study of MEDI4736 (durvalumab) in subjects with glioblastoma (GBM) enrolled into 5 non-comparative cohorts. Primary study objectives, which vary by cohort due to differences in subject populations, include evaluation of the clinical efficacy as measured by the overall survival (OS) rate at 12 months (Cohort A), progression-free survival (PFS) at 6 months (Cohorts B, B2, and B3), and OS at 6 months (Cohort C). For all cohorts, secondary objectives include evaluation of the safety/tolerability and clinical efficacy of study treatment, and exploratory objectives include evaluation of the neurologic function and correlative biomarkers.

Detailed Description

Eligible subjects are enrolled in parallel into one of the following 5 cohorts as described below. In each cohort, the first study drug administration for the first subject and the second subject are separated by at least 1 week.

  • Cohort A: Subjects with newly diagnosed unmethylated O^6-methylguanine-deoxyribonucleic acid methyltransferase (MGMT) GBM receive durvalumab (10 mg/kg every 2 weeks [Q2W]) + standard radiotherapy. The first 6 subjects are evaluated for dose-limiting toxicity (DLT) for 10 weeks to determine whether the durvalumab dose should be lowered to 3 or 1 mg/kg.
  • Cohort B: Bevacizumab-naïve subjects with recurrent GBM receive durvalumab (10 mg/kg Q2W) as monotherapy.
  • Cohort B2: Bevacizumab-naïve subjects with recurrent GBM receive durvalumab (10 mg/kg Q2W) + bevacizumab (10 mg/kg Q2W).
  • Cohort B3: Bevacizumab-naïve subjects with recurrent GBM receive durvalumab (10 mg/kg Q2W) + bevacizumab (3 mg/kg Q2W).
  • Cohort C: Bevacizumab-refractory subjects with recurrent GBM receive durvalumab (10 mg/kg Q2W) + continued bevacizumab (10 mg/kg Q2W). The first 6 subjects are evaluated for DLTs for 6 weeks to determine whether the durvalumab dose should be lowered to 3 or 1 mg/kg.

The Core Study lasts for up to 12 months; optional extension treatment may be offered to subjects who complete 51 weeks of treatment on the Core Study with stable disease or better and upon agreement between the subject, Investigator, and Sponsor.

Subjects are followed on study for 90 days after the last drug administration and off study every 6 months for 3 years from the date of the first dose of study treatment.

The primary study endpoints have been met, although some subjects remain in treatment and/or follow-up and data collection is ongoing.

Study Design

Study Type
Interventional
Allocation
Non Randomized
Intervention Model
Parallel
Primary Purpose
Treatment
Masking
None

Eligibility Criteria

Ages
18 Years to — (Adult, Older Adult)
Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Not provided

Exclusion Criteria

  • Not provided

Arms & Interventions

Cohort A

Experimental

Subjects with newly diagnosed unmethylated MGMT GBM receive durvalumab (10 mg/kg Q2W) + standard radiotherapy.

Intervention: Durvalumab (Drug)

Cohort B3

Experimental

Bevacizumab-naïve subjects with recurrent GBM receive durvalumab (10 mg/kg Q2W) + bevacizumab (3 mg/kg Q2W).

Intervention: Durvalumab (Drug)

Cohort A

Experimental

Subjects with newly diagnosed unmethylated MGMT GBM receive durvalumab (10 mg/kg Q2W) + standard radiotherapy.

Intervention: Standard radiotherapy (Radiation)

Cohort B

Experimental

Bevacizumab-naïve subjects with recurrent GBM receive durvalumab (10 mg/kg Q2W) as monotherapy.

Intervention: Durvalumab (Drug)

Cohort B2

Experimental

Bevacizumab-naïve subjects with recurrent GBM receive durvalumab (10 mg/kg Q2W) + bevacizumab (10 mg/kg Q2W).

Intervention: Durvalumab (Drug)

Cohort B2

Experimental

Bevacizumab-naïve subjects with recurrent GBM receive durvalumab (10 mg/kg Q2W) + bevacizumab (10 mg/kg Q2W).

Intervention: Bevacizumab (Biological)

Cohort B3

Experimental

Bevacizumab-naïve subjects with recurrent GBM receive durvalumab (10 mg/kg Q2W) + bevacizumab (3 mg/kg Q2W).

Intervention: Bevacizumab (Biological)

Cohort C

Experimental

Bevacizumab-refractory subjects with recurrent GBM receive durvalumab (10 mg/kg Q2W) + continued bevacizumab (10 mg/kg Q2W).

Intervention: Durvalumab (Drug)

Cohort C

Experimental

Bevacizumab-refractory subjects with recurrent GBM receive durvalumab (10 mg/kg Q2W) + continued bevacizumab (10 mg/kg Q2W).

Intervention: Bevacizumab (Biological)

Outcomes

Primary Outcomes

Overall Survival Rate at 12 Months (OS-12) as Estimated Using the Kaplan-Meier Method (Cohort A)

Time Frame: Up to 12 months

OS-12 with 90% confidence interval (CI) is the primary endpoint of Cohort A and is the percentage of subjects who remain alive at 12 months, where OS is measured from the time of diagnosis until the recorded date of death or last follow-up. Subjects who are lost to follow-up at the time of the analysis will be censored on the date of last follow-up.

Progression-free Survival Rate at 6 Months (PFS-6) as Estimated Using the Kaplan-Meier Method (Cohorts B, B2, and B3)

Time Frame: Up to 6 months

PFS-6 is the primary endpoint of Cohorts B, B2, and B3, and is the percentage of subjects who have not progressed at 6 months, with PFS measured from the date of the first dose of study treatment to the date of earliest disease progression (PD) based on modified Response Assessment in Neuro-Oncology (RANO) criteria or to the date of death, if PD does not occur. Per the RANO criteria, PD indicates any new lesion or a 25% increase in sum of the products of perpendicular diameters of enhancing lesions, or clear clinical deterioration per the Investigator (Wen et al. J Clin Oncol 2010; 28(11):1963-72).

Overall Survival Rate at 6 Months (OS-6) as Estimated Using the Kaplan-Meier Method (Cohort C)

Time Frame: Up to 6 months

OS-6 is the primary endpoint of Cohort C and is the percentage of subjects who remain alive at 6 months, where OS is measured from the date of the first dose of study treatment until the recorded date of death or last follow-up. Subjects who are lost to follow-up at the time of the analysis will be censored on the date of last follow-up.

Secondary Outcomes

  • Number of Participants With Treatment-emergent Adverse Events(Up to 15 months)
  • Median OS as Estimated Using the Kaplan-Meier Method(Up to 36 months)
  • Number of Subjects With Best Overall Response(Up to 15 months)
  • Mean Changes From Baseline in the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC-QLQ-C30)(Up to 12 months)
  • Mean Changes From Baseline in the EORTC Brain Cancer Quality of Life Questionnaire (EORTC-QLQ-BN-20)(Up to 12 months)
  • Median PFS as Estimated Using the Kaplan-Meier Method(Up to 15 months)

Investigators

Sponsor Class
Other
Responsible Party
Sponsor

Study Sites (1)

Loading locations...

Similar Trials