NCT03406650

Neoadjuvant and Adjuvant Durvalumab in Combination With Neoadjuvant Chemotherapy in Patients With Operable Urothelial Cancer.

Neoadjuvant and Adjuvant Durvalumab in Combination With Neoadjuvant Chemotherapy in Patients With Operable Urothelial Cancer. A Multicenter, Single-arm Phase II Trial

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 61 (actual)
• Sponsor: Swiss Cancer Institute · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The main objective is to demonstrate that the addition of neoadjuvant and adjuvant immunotherapy with durvalumab, to standard neoadjuvant chemotherapy (with cisplatin/gemcitabine) and surgery in urothelial carcinoma could improve event-free survival.

Detailed description

Despite optimal surgical management the prognosis for localized muscle invasive urothelial cancer (MIUC) is unfavorable with 5-year overall survival of around 45%. According to international guidelines the use of cisplatin-based neoadjuvant chemotherapy is considered standard of care in all patients with localized MIUC with planned curative local treatment. However, the benefit of neoadjuvant chemotherapy is limited and there is a clear medical need for improvement for this patient population. Durvalumab has been tested in a phase I/II open-label study including patients with metastatic urothelial cancer (mUC). The results demonstrated an overall response rate (RR) of 31% in 42 response-evaluable patients. The side effect profile was favorable with most common grade 1/2 AE representing fatigue (13%), diarrhea (10%) and decreased appetite (8%). Three patients (4.9%) had treatment related grade 3 AE's, no grade 4/5 events were noted. The combination of cisplatin/gemcitabine chemotherapy with modern immune-checkpoint inhibition has been demonstrated to be feasible with demonstration of favorable immunomodulatory effects. In view of these data it appears a logical step to apply these novel agents in the curative setting of neoadjuvant treatment. The expected benefit of combining chemotherapy with durvalumab and to continue durvaluamb postoperatively might be twofold: * to increase the response rate in the pre-operative setting and subsequently to increase the rate of pathologic complete remission (pT0) and to reduce risk of local recurrence * to evoke durable systemic anti-cancer responses and subsequently to increase disease free- and overall survival and furthermore to induce antitumor immune response.

Conditions

• Urothelial Cancer

Interventions

Type	Name	Description
DRUG	Neoadjuvant and adjuvant durvalumab	Neoadjuvant durvalumab 1500 mg q3w for 4 cycles Adjuvant durvalumab 1500 mg q4w for 10 cycles

Timeline

• Start date: 2018-05-15
• Primary completion: 2022-02-25
• Completion: 2025-01-31
• First posted: 2018-01-23
• Last updated: 2025-05-04

Locations

17 sites across 2 countries: Germany, Switzerland