Clinical trial NCT03732677: Durvalumab+ Gemcitabine/Cisplatin (Neoadjuvant Treatment) and Durvalumab (Adjuvant Treatment) in Patients With MIBC
Official title: A Phase III, Randomized, Open-Label, Multi-Center, Global Study to Determine the Efficacy and Safety of Durvalumab in Combination With Gemcitabine+Cisplatin for Neoadjuvant Treatment Followed by Durvalumab Alone for Adjuvant Treatment in Patients With Muscle-Invasive Bladder Cancer.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Muscle Invasive Bladder Cancer
Keywords: Bladder Cancer
Immunotherapy
PD-L1
Durvalumab (MEDI4736)
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2018-11-06
Enrollment: 1063
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A Global Study to Determine the Efficacy and Safety of Durvalumab in Combination with Gemcitabine+Cisplatin for Neoadjuvant Treatment and Durvalumab Alone for Adjuvant Treatment in Patients with Muscle-Invasive Bladder Cancer


Eligibility criteria: Inclusion:

* Patient resectable muscle-invasive bladder cancer with clinical stage T2-T4aN0/1M0 with transitional and mixed transitional cell histology
* Patients must be planning to undergo a radical cystectomy
* Patients who have not received prior systemic chemotherapy or immunotherapy for treatment of MIBC
* ECOG performance status of 0 or 1
* Must have a life expectancy of at least 12 weeks at randomization

Exclusion:

* Evidence of lymph node (N2-N3) or metastatic (M1) disease at time of screening.
* Prior pelvic radiotherapy treatment within 2 years of randomization to study
* Prior exposure to immune-mediated therapy (with exclusion of Bacillus-Calmette Guerin \[BCG\]), including but not limited to other anti-CTLA-4, anti-PD-1, anti PD-L1, or anti-PD-L2 antibodies.
* Current or prior use of immunosuppressive medication within 14 days before the first dose of investigational product (IP). The following are exceptions to this criterion: Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra articular injection); Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent; Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication)
* Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.
* Uncontrolled intercurrent illness
* Active infection including Tuberculosis, Hepatitis B, Hepatitis C, and Human Immunodeficiency

Primary outcomes:
measure: Pathologic complete response (pCR) rates at time of cystectomy
timeFrame: Up to 6 months
measure: Event-free survival (EFS) per central review defined as time from randomization to event
timeFrame: Up to 48 months
Secondary outcomes:
measure: Proportion of patients who achieve <P2 at time of cystectomy
timeFrame: Up to 6 months
measure: EFS at 24 months (EFS24) defined as time from randomization to event
timeFrame: Up to 24 months
measure: Proportion of patients who undergo cystectomy
timeFrame: Up to 6 months
measure: Overall survival rate at 5 years
timeFrame: Up to 60 months
measure: PFS2 defined as time from randomization to event following subsequent therapy
timeFrame: Up to 84 months
measure: Safety and Tolerability as evaluated by adverse events occurring throughout the study
timeFrame: Up to 84 months
measure: Immunogenicity of durvalumab when used in combination with gemcitabine/cisplatin as measured by presence of antidrug antibodies (ADA)
timeFrame: Up to 12 months
measure: Overall Survival
timeFrame: Up to 84 months
measure: Metastasis-free survival per investigator assessment or local biopsy review.
timeFrame: Up to 48 months
measure: Disease-specific survival per investigator assessment or local biopsy review.
timeFrame: up to 48 months
measure: Disease-free survival
timeFrame: Up to 48 months
Other outcomes:
Locations:
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country: Korea, Republic of
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city: Novosibirsk
country: Russian Federation
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city: Samara
country: Russian Federation
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city: St Petersburg
country: Russian Federation
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city: St. Petersburg
country: Russian Federation
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city: St. Petersburg
country: Russian Federation
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country: Turkey
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city: Hanoi
country: Vietnam
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city: Ho Chi Minh
country: Vietnam
facility: Research Site
city: Hochiminh
country: Vietnam
facility: Research Site
Study officials:
References: