A Single-arm, Phase II Study of Durvalumab (MEDI4736) and Tremelimumab for Relapsed/Refractory Germ Cell Tumors

Memorial Sloan Kettering Cancer Center7 sites in 1 country30 target enrollmentMay 15, 2017

ConditionsGerm Cell Tumor Nonseminomatous Germ Cell Tumor Seminoma Germinomatous Germ Cell Tumor Dysgerminoma Pineal Germ Cell Tumor

InterventionsDurvalumab Tremelimumab

Overview

Phase: Phase 2
Intervention: Durvalumab
Conditions: Germ Cell Tumor
Sponsor: Memorial Sloan Kettering Cancer Center
Enrollment: 30
Locations: 7
Primary Endpoint: overall response rate (ORR)
Status: Active, not recruiting
Last Updated: 3 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study is to test the safety and effectiveness of durvalumab with tremelimumab in patients with relapsed or refractory germ cell tumors.

Registry

clinicaltrials.gov

Start Date

May 15, 2017

End Date

November 1, 2026

Last Updated

3 months ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Memorial Sloan Kettering Cancer Center

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Age ≥ 18 years at time of informed consent
•Body weight \> 30 kg
•Histologically confirmed diagnosis of GCT (nonseminoma or seminoma in men; non-dysgerminomas, dysgerminomas, or germinomas in women or patients with pineal gland GCT) at MSKCC of any primary site (includes female GCT and intracranial GCT).
•Evidence of measurable disease either by RECIST 1.1 or elevation of serum tumor markers (AFP \> 15 ng/mL or HCG \>2.2 mIU/ml).
•Patients must have progressed after at least one prior systemic therapy for GCT and meet one of the following criteria:
•a. Patients with evidence of progressive or recurrent GCT after progression prior high dose chemotherapy (HDCT) treatment, defined as meeting at least on of the following criteria: i. Tumor biopsy of new or growing or unresectable lesions demonstrating viable GCT. In the event of an incomplete gross resection where viable GCT is found, patients will be considered eligible for this study.
•ii. Consecutive elevated serum tumor markers (HCG or AFP) that are increasing. Increase of an elevated LDH alone does not constitute progressive disease.
•iii. Development of new or enlarging lesions in the the setting of persistently elevated HCG or AFP, even if the HCG and AFP are not continuing to rise.
•b. Patients deemed not to be a candidate for or benefit from potentially curative HDCT or other curative treatment options defined as follows: i. Patients with inadequate renal function for HDCT. ii. Patients who have had 3 or more lines of prior chemotherapy as this patient population has historically not benefitted from HDCT.
•iii. Patients with late relapse (relapse \> 2 years after last therapy) as this patient population has historically not benefitted from HDCT.

Exclusion Criteria

•Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
•Previous enrolment in the present study
•Participation in another clinical study with an investigational product during the last 14 days
•Mean QT interval corrected for heart rate (QTc) ≥ 470 ms calculated from 3 electrocardiograms (ECGs) using Fredericia's Correction
•Any previous treatment with a PD-1 or PD-L1 inhibitor, including durvalumab or an anti-CTLA-4, including tremelimumab
•Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) ≤ 14 days prior to the first dose of study drug
•Major surgery within 28 days of starting study treatment. There is no minimum time requirement for minor procedures such as biopsy or vascular access placement.
•Radiation within 14 days of starting study treatment
•Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab or tremelimumab. The following are exceptions to this criterion:
•Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)

Arms & Interventions

Duravalumab + Tremelimumab

Duravalumab/Tremelimumab: Durvalumab and Tremelimumab will be administered by IV every 4 weeks for up to 4 doses/cycles, then Durvalumab by IV every 4 weeks starting at Week 16 for 9 doses (total treatment duration of 12 months). Participants enrolled now will receive tremelimumab \*300mg with durvalumab 1500mg for 1 cycle followed by 12 cycles of durvalumab 1500mg every 4 weeks or until lack of clinical benefit or unacceptable toxicity.

Intervention: Durvalumab