NCT02794883

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

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 36 (actual)
• Sponsor: Northwestern University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

PRIMARY OBJECTIVES: I. To determine the T-cell changes that occur in glioblastoma (GBM) treated with tremelimumab and durvalumab (MEDI4736) as single agents and in combination. SECONDARY OBJECTIVES: I. To evaluate the safety of either tremelimumab or MEDI4736 alone and in combination in patients with GBM. II. To determine the time to progression for patients treated with either tremelimumab or MEDI4736 alone and in combination of both, post-surgery. III. To determine the overall survival for patients treated with tremelimumab or MEDI4736 alone and in combination of both post-surgery. IV. To assess magnetic resonance imaging (MRI) changes in patients treated with either tremelimumab or MEDI4736 alone and in combination of both post-surgery. TERTIARY OBJECTIVES: I. To correlate T-cell changes and programmed death ligand 1 (PDL1) expression with patient outcomes. OUTLINE: Patients are randomized to 1 of 3 arms. ARM 1: Patients receive tremelimumab intravenously (IV) over 1 hour on day 1. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. ARM 2: Patients 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. ARM 3: Patients receive tremelimumab IV over 1 hour on day 1 then, after a gap of 1 hour for the first cycle, durvalumab IV over 1 hour on days 1 and 15. Courses repeat every 4 weeks with tremelimumab for up to 7 courses and every 2 weeks with durvalumab for up to 14 courses. Patients then receive both tremelimumab and durvalumab IV over 1 hour every 12 weeks in the absence of disease progression or unacceptable toxicity. All patients undergo surgical tumor resection on day 14. After completion of study treatment, patients are followed up every 8-16 weeks for 2 years.

Conditions

• Malignant Glioma
• Recurrent Glioblastoma

Interventions

Type	Name	Description
BIOLOGICAL	Durvalumab	Given IV
OTHER	Laboratory Biomarker Analysis	Correlative Studies
PROCEDURE	Surgical Procedure	Undergo surgical tumor resection
BIOLOGICAL	Tremelimumab	Given IV

Timeline

• Start date: 2016-11-01
• Primary completion: 2018-05-09
• Completion: 2020-06-17
• First posted: 2016-06-09
• Last updated: 2022-04-18
• Results posted: 2022-04-18

Locations

1 site across 1 country: United States