Ignite Creation Date:
2025-12-25 @ 4:59 AM
Ignite Modification Date:
2025-12-26 @ 3:59 AM
Study NCT ID:
NCT03912818
Status:
TERMINATED
Last Update Posted:
2023-09-11
First Post:
2019-04-08
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
Durvalumab and Standard Chemotherapy Before Surgery in Treating Patients With Variant Histology Bladder Cancer
Sponsor:
Stanford University
Organization:
Study Overview
Official Title:
Phase 2 Open Label Study of Durvalumab With Neoadjuvant Chemotherapy in Variant Histology Bladder Cancer
Status:
TERMINATED
Status Verified Date:
2023-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Difficulty with enrollment
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase II trial studies the side effects of durvalumab and chemotherapy before surgery in treating patients with variant histology bladder cancer. Immunotherapy with monoclonal antibodies, such as durvalumab, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as methotrexate, vinblastine, doxorubicin, cisplatin, gemcitabine, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving durvalumab in addition to standard chemotherapy may lead to better outcomes in patients with variant histology bladder cancer.
Detailed Description:
PRIMARY OBJECTIVES:
I. To assess the safety and tolerability of durvalumab in combination with chemotherapy in subjects with variant histology bladder cancer.
SECONDARY OBJECTIVES:
I. To determine the percent of subjects post-neoadjuvant chemo-immunotherapy who achieve tumor stage of pT2 N0 M0 or better (pT1 N0 or pT0) at cystectomy.
II. To assess the response rate (RR) in post-neoadjuvant chemo immunotherapy as assessed by the investigator using imaging at screening and post treatment.
III. To assess the molecular characterization of tumor tissue pre-neoadjuvant therapy and at post treatment cystectomy (for subject who have persistent disease).
IV. To determine circulating free deoxyribonucleic acid (DNA) (cfDNA) (cell free DNA) at baseline, during treatment and following post treatment cystectomy using Natera sequencing platform.
OUTLINE: Patients are assigned to 1 of 3 cohorts.
COHORT I: Patients receive durvalumab intravenously (IV) over 60 minutes on day 1. Chemotherapeutic agents will be administered as an IV infusion according to prescribing information or treatment guidance in general use by the Investigating site. Methotrexate on day 1, vinblastine IV on day 2, doxorubicin IV on day 2, and cisplatin IV on day 2. Cycles repeat every 14 days up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo cystectomy within 6 weeks.
COHORT II: Patients receive durvalumab IV over 60 minutes on day 1. Chemotherapeutic agents will be administered as an IV infusion according to prescribing information or treatment guidance in general use by the Investigating site. Cisplatin IV over 60 minutes on day 1, and gemcitabine IV on days 1 and 8. Cycles repeat every 21 days up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo cystectomy within 6 weeks.
COHORT III: Patients receive durvalumab IV over 60 minutes on day 1.Chemotherapeutic agents will be administered as an IV infusion according to prescribing information or treatment guidance in general use by the Investigating site. Carboplatin IV on day 1, and gemcitabine IV on days 1 and 8. Cycles repeat every 21 days up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo cystectomy within 6 weeks.
After surgery, patients are followed up at 30 and 90 days.
I. To assess the safety and tolerability of durvalumab in combination with chemotherapy in subjects with variant histology bladder cancer.
SECONDARY OBJECTIVES:
I. To determine the percent of subjects post-neoadjuvant chemo-immunotherapy who achieve tumor stage of pT2 N0 M0 or better (pT1 N0 or pT0) at cystectomy.
II. To assess the response rate (RR) in post-neoadjuvant chemo immunotherapy as assessed by the investigator using imaging at screening and post treatment.
III. To assess the molecular characterization of tumor tissue pre-neoadjuvant therapy and at post treatment cystectomy (for subject who have persistent disease).
IV. To determine circulating free deoxyribonucleic acid (DNA) (cfDNA) (cell free DNA) at baseline, during treatment and following post treatment cystectomy using Natera sequencing platform.
OUTLINE: Patients are assigned to 1 of 3 cohorts.
COHORT I: Patients receive durvalumab intravenously (IV) over 60 minutes on day 1. Chemotherapeutic agents will be administered as an IV infusion according to prescribing information or treatment guidance in general use by the Investigating site. Methotrexate on day 1, vinblastine IV on day 2, doxorubicin IV on day 2, and cisplatin IV on day 2. Cycles repeat every 14 days up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo cystectomy within 6 weeks.
COHORT II: Patients receive durvalumab IV over 60 minutes on day 1. Chemotherapeutic agents will be administered as an IV infusion according to prescribing information or treatment guidance in general use by the Investigating site. Cisplatin IV over 60 minutes on day 1, and gemcitabine IV on days 1 and 8. Cycles repeat every 21 days up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo cystectomy within 6 weeks.
COHORT III: Patients receive durvalumab IV over 60 minutes on day 1.Chemotherapeutic agents will be administered as an IV infusion according to prescribing information or treatment guidance in general use by the Investigating site. Carboplatin IV on day 1, and gemcitabine IV on days 1 and 8. Cycles repeat every 21 days up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo cystectomy within 6 weeks.
After surgery, patients are followed up at 30 and 90 days.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?: