Trial Outcomes & Findings for Durvalumab and Standard Chemotherapy Before Surgery in Treating Patients With Variant Histology Bladder Cancer (NCT NCT03912818)

Last Updated: 2023-09-11

Results Overview

Graded per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. The safety and tolerability of durvalumab in combination with chemotherapy in subjects with variant histology bladder cancer who initiate study treatment will be assessed as the number, by treatment cohort, of grade 3, 4, or 5 adverse events, considered probably or definitely related by the investigator.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

7 participants

Primary outcome timeframe

At 120 days

Results posted on

2023-09-11

Participant Flow

7 patients signed informed consent; 6 were assigned to treatment

Participant milestones

Participant milestones
Measure	Cohort I (Durvalumab, DD MVAC) Durvalumab (MEDI4736), at1500 mg fixed dose, administered intravenously (IV) over 60 minutes. Standard chemotherapy will be administered as an IV infusion during each of the 4 cycles. Dose Dense Methotrexate, Vinblastine, Doxorubicin, Cisplatin (DD MVAC), in 14 day cycles (2 weeks), Methotrexate 30 mg/m2 on Cycle Day 1, Vinblastine 3 mg/m2 on Cycle Day 2, Doxorubicin 30 mg/m2 on Cycle Day 2 and Cisplatin 70 mg/m2 on Cycle Day 2. Patients undergo cystectomy within 6 weeks.	Cohort III (Durvalumab, Carbo-gem) Durvalumab (MEDI4736), at 1500 mg fixed dose, administered intravenously (IV) over 60 minutes. Standard chemotherapy will be administered as an IV infusion during each of the 4 cycles. Carboplatin: AUC 5 on Cycle Day 1 and gemcitabine 1,000 mg/m2 on Cycle Day 1 and Day 8 in 21 day cycles (3 weeks). Patients undergo cystectomy within 6 weeks.
Overall Study STARTED	3	3
Overall Study COMPLETED	3	3
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Durvalumab and Standard Chemotherapy Before Surgery in Treating Patients With Variant Histology Bladder Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort I (Durvalumab, DD MVAC) n=3 Participants Durvalumab (MEDI4736), at1500 mg fixed dose, administered intravenously (IV) over 60 minutes. Standard chemotherapy will be administered as an IV infusion during each of the 4 cycles. Dose Dense Methotrexate, Vinblastine, Doxorubicin, Cisplatin (DD MVAC), in 14 day cycles (2 weeks), Methotrexate 30 mg/m2 on Cycle Day 1, Vinblastine 3 mg/m2 on Cycle Day 2, Doxorubicin 30 mg/m2 on Cycle Day 2 and Cisplatin 70 mg/m2 on Cycle Day 2. Patients undergo cystectomy within 6 weeks.	Cohort III (Durvalumab, Carbo-gem) n=3 Participants Durvalumab (MEDI4736), at 1500 mg fixed dose, administered intravenously (IV) over 60 minutes. Standard chemotherapy will be administered as an IV infusion during each of the 4 cycles. Carboplatin: AUC 5 on Cycle Day 1 and gemcitabine 1,000 mg/m2 on Cycle Day 1 and Day 8 in 21 day cycles (3 weeks). Patients undergo cystectomy within 6 weeks.	Total n=6 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants

PRIMARY outcome

Timeframe: At 120 days

Outcome measures

Outcome measures
Measure	Cohort I (Durvalumab, DD MVAC) n=3 Participants Durvalumab (MEDI4736), at1500 mg fixed dose, administered intravenously (IV) over 60 minutes. Standard chemotherapy will be administered as an IV infusion during each of the 4 cycles. Dose Dense Methotrexate, Vinblastine, Doxorubicin, Cisplatin (DD MVAC), in 14 day cycles (2 weeks), Methotrexate 30 mg/m2 on Cycle Day 1, Vinblastine 3 mg/m2 on Cycle Day 2, Doxorubicin 30 mg/m2 on Cycle Day 2 and Cisplatin 70 mg/m2 on Cycle Day 2. Patients undergo cystectomy within 6 weeks.	Cohort III (Durvalumab, Carbo-gem) n=3 Participants Durvalumab (MEDI4736), at 1500 mg fixed dose, administered intravenously (IV) over 60 minutes. Standard chemotherapy will be administered as an IV infusion during each of the 4 cycles. Carboplatin: AUC 5 on Cycle Day 1 and gemcitabine 1,000 mg/m2 on Cycle Day 1 and Day 8 in 21 day cycles (3 weeks). Patients undergo cystectomy within 6 weeks.
Incidence of Grade 3-5 Adverse Events Grade 5	0 events	0 events
Incidence of Grade 3-5 Adverse Events Grade 3	1 events	2 events
Incidence of Grade 3-5 Adverse Events Grade 4	0 events	0 events

SECONDARY outcome

Timeframe: At 20 weeks

Population: Participants who underwent renal cystectomy are included in the analysis.

Achievement of tumor staging will be determined by pathologist at cystectomy and reported by treatment cohort. Assessed per National Comprehensive Cancer Network bladder cancer guidelines. * T0 N0 M0 = No evidence of primary tumor * T1 N0 M0 = Tumor staging by pathological assessment detected in lamina propria (T0), with no tumor positive nodes (N0). * T2 N0 M0 = Tumor staging by pathological assessment detected in muscularis propria (pT2), with no tumor positive nodes (N0) or tumor metastases (M0) observed.

Outcome measures

Outcome measures
Measure	Cohort I (Durvalumab, DD MVAC) n=3 Participants Durvalumab (MEDI4736), at1500 mg fixed dose, administered intravenously (IV) over 60 minutes. Standard chemotherapy will be administered as an IV infusion during each of the 4 cycles. Dose Dense Methotrexate, Vinblastine, Doxorubicin, Cisplatin (DD MVAC), in 14 day cycles (2 weeks), Methotrexate 30 mg/m2 on Cycle Day 1, Vinblastine 3 mg/m2 on Cycle Day 2, Doxorubicin 30 mg/m2 on Cycle Day 2 and Cisplatin 70 mg/m2 on Cycle Day 2. Patients undergo cystectomy within 6 weeks.	Cohort III (Durvalumab, Carbo-gem) n=2 Participants Durvalumab (MEDI4736), at 1500 mg fixed dose, administered intravenously (IV) over 60 minutes. Standard chemotherapy will be administered as an IV infusion during each of the 4 cycles. Carboplatin: AUC 5 on Cycle Day 1 and gemcitabine 1,000 mg/m2 on Cycle Day 1 and Day 8 in 21 day cycles (3 weeks). Patients undergo cystectomy within 6 weeks.
Proportion of Subjects Who Initiate Study Treatment and Achieve Tumor Stage of pT2 N0 M0 or Better (e.g., pT0, pT1 N0) at Cystectomy	1 Participants	1 Participants

Adverse Events

Cohort I (Durvalumab, DD MVAC)

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Cohort III (Durvalumab, Carbo-gem)

Serious events: 3 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cohort I (Durvalumab, DD MVAC) n=3 participants at risk Durvalumab (MEDI4736), at1500 mg fixed dose, administered intravenously (IV) over 60 minutes. Standard chemotherapy will be administered as an IV infusion during each of the 4 cycles. Dose Dense Methotrexate, Vinblastine, Doxorubicin, Cisplatin (DD MVAC), in 14 day cycles (2 weeks), Methotrexate 30 mg/m2 on Cycle Day 1, Vinblastine 3 mg/m2 on Cycle Day 2, Doxorubicin 30 mg/m2 on Cycle Day 2 and Cisplatin 70 mg/m2 on Cycle Day 2. Patients undergo cystectomy within 6 weeks.	Cohort III (Durvalumab, Carbo-gem) n=3 participants at risk Durvalumab (MEDI4736), at 1500 mg fixed dose, administered intravenously (IV) over 60 minutes. Standard chemotherapy will be administered as an IV infusion during each of the 4 cycles. Carboplatin: AUC 5 on Cycle Day 1 and gemcitabine 1,000 mg/m2 on Cycle Day 1 and Day 8 in 21 day cycles (3 weeks). Patients undergo cystectomy within 6 weeks.
Infections and infestations Abcess	33.3% 1/3 • Time of Consent to end of study treatment plus 90 days (average approximately 20 weeks)	0.00% 0/3 • Time of Consent to end of study treatment plus 90 days (average approximately 20 weeks)
Blood and lymphatic system disorders Hypercapnia	33.3% 1/3 • Time of Consent to end of study treatment plus 90 days (average approximately 20 weeks)	0.00% 0/3 • Time of Consent to end of study treatment plus 90 days (average approximately 20 weeks)
Cardiac disorders Cardiopulmonary Arrest	33.3% 1/3 • Time of Consent to end of study treatment plus 90 days (average approximately 20 weeks)	0.00% 0/3 • Time of Consent to end of study treatment plus 90 days (average approximately 20 weeks)
Blood and lymphatic system disorders Anemia	0.00% 0/3 • Time of Consent to end of study treatment plus 90 days (average approximately 20 weeks)	33.3% 1/3 • Time of Consent to end of study treatment plus 90 days (average approximately 20 weeks)
Renal and urinary disorders Ureteral Obstruction with increased creatinine	33.3% 1/3 • Time of Consent to end of study treatment plus 90 days (average approximately 20 weeks)	0.00% 0/3 • Time of Consent to end of study treatment plus 90 days (average approximately 20 weeks)
Surgical and medical procedures Small Intestine Anastomotic Leak	0.00% 0/3 • Time of Consent to end of study treatment plus 90 days (average approximately 20 weeks)	33.3% 1/3 • Time of Consent to end of study treatment plus 90 days (average approximately 20 weeks)
Surgical and medical procedures Ureteric Anastomotic Leak	0.00% 0/3 • Time of Consent to end of study treatment plus 90 days (average approximately 20 weeks)	33.3% 1/3 • Time of Consent to end of study treatment plus 90 days (average approximately 20 weeks)
Blood and lymphatic system disorders Sepsis	0.00% 0/3 • Time of Consent to end of study treatment plus 90 days (average approximately 20 weeks)	33.3% 1/3 • Time of Consent to end of study treatment plus 90 days (average approximately 20 weeks)
Cardiac disorders Heart Failure	0.00% 0/3 • Time of Consent to end of study treatment plus 90 days (average approximately 20 weeks)	33.3% 1/3 • Time of Consent to end of study treatment plus 90 days (average approximately 20 weeks)
Gastrointestinal disorders Abdominal Pain	0.00% 0/3 • Time of Consent to end of study treatment plus 90 days (average approximately 20 weeks)	33.3% 1/3 • Time of Consent to end of study treatment plus 90 days (average approximately 20 weeks)
General disorders Dehydration	0.00% 0/3 • Time of Consent to end of study treatment plus 90 days (average approximately 20 weeks)	33.3% 1/3 • Time of Consent to end of study treatment plus 90 days (average approximately 20 weeks)
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/3 • Time of Consent to end of study treatment plus 90 days (average approximately 20 weeks)	33.3% 1/3 • Time of Consent to end of study treatment plus 90 days (average approximately 20 weeks)

Other adverse events

Additional Information

Sandy Srinivas

Stanford University

Phone: 650-725-2078

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place