A Phase II Trial of Durvalumab (MEDI4736) and Tremelimumab in Metastatic, Non-transitional Cell Carcinoma of the Urothelial Tract

Memorial Sloan Kettering Cancer Center4 sites in 1 country15 target enrollmentJanuary 31, 2018

ConditionsNon-Transitional Cell Carcinoma of the Urothelial Tract Small Cell of the Bladder Adenocarcinoma of the Bladder Squamous Cell Carcinoma of the Bladder Metastatic Bladder Cancer

Interventionsdurvalumab and tremelimumab

Drugsdurvalumab and tremelimumab

Overview

Phase: Phase 2
Intervention: durvalumab and tremelimumab
Conditions: Non-Transitional Cell Carcinoma of the Urothelial Tract
Sponsor: Memorial Sloan Kettering Cancer Center
Enrollment: 15
Locations: 4
Primary Endpoint: Overall Response Rate
Status: Completed
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This study is being done test to test the safety and effectiveness of durvalumab combined with tremelimumab in patients who have a rare form of cancer of the urinary tract.

Registry

clinicaltrials.gov

Start Date

January 31, 2018

End Date

February 10, 2021

Last Updated

4 years 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 or cytologically confirmed small cell carcinoma, squamous cell carcinoma or adenocarcinoma (confirmed at MSKCC) of the bladder, ureter, urethra, urachus, or renal pelvis. Patients with squamous cell carcinoma and adenocarcinoma are required to have a predominant squamous or adenocarcinoma component as reviewed by the pathologist at MSKCC. However, if any element of small cell or neuroendocrine differentiation is present, the patients will be classified as small cell/neuroendocrine.
•Confirmation of availability of sufficient tissue from a prior surgery for correlative studies is required prior to enrollment. Patients must have representative non-TCC or the urothelial tract FFPE archival tumor specimens (tumor blocks or 30 unstained slides; preference for tumor blocks). These samples may be submitted between the time of consent and the start of treatment. Patients with \< 30 slides may be enrolled after discussion with the principal or co-principal investigators.
•Clinical evidence of metastatic (T4b, any N; any T, N2-3; M1) disease.
•Life expectancy of 12 weeks of greater based on assessment by the treating investigator.
•Evidence of measurable disease by RECIST 1.
•Patients with small cell carcinoma must have progressed after at least one prior systemic therapy. Patients with squamous cell carcinoma or adenocarcinoma may be previously untreated or have progressed after prior systemic therapy. Chemotherapy administered in conjunction with primary radiation as a radio-sensitizer WILL be counted as a systemic chemotherapy regimen. NOTE: There is no maximum number of prior treatments allowed.
•Patients with brain metastases are allowed onto the study as long as patients have completed their treatment for brain metastasis, no longer require corticosteroids, and are asymptomatic. Subjects with neurological symptoms should undergo a head CT scan or brain MRI to exclude brain metastasis, at the discretion of the treating physician.
•Eastern Cooperative Oncology Group (ECOG) performance status of 0-

Exclusion Criteria

•Previous enrollment 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) \< 21 days prior to enrollment.
•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 14 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)
•Systemic corticosteroids at physiologic doses not to exceed \<\<10 mg/day\>\> of prednisone or its equivalent

Arms & Interventions

combination of durvalumab and tremelimumab

Patients will receive durvalumab 1500 mg and tremelimumab 75 mg IV Q4W for up to 4 doses/cycles, then durvalumab 1500 mg Q4W starting at Week 16 for 9 doses (total treatment duration of 12 months).

Intervention: durvalumab and tremelimumab