A Study of Atezolizumab Versus Observation as Adjuvant Therapy in Participants With High-Risk Muscle-Invasive Urothelial Carcinoma (UC) After Surgical Resection

• Register: ClinicalTrials.gov
• Last refreshed on: 27 February 2023
• Main ID: NCT02450331
• Date of registration: 19/05/2015
• Prospective Registration: Yes
• Primary sponsor: Hoffmann-La Roche
• Public title: A Study of Atezolizumab Versus Observation as Adjuvant Therapy in Participants With High-Risk Muscle-Invasive Urothelial Carcinoma (UC) After Surgical Resection IMvigor010
• Scientific title: A Phase III, Open-Label, Multicenter, Randomized Study of Atezolizumab (Anti-PD-L1 Antibody) Versus Observation as Adjuvant Therapy in Patients With High-Risk Muscle-Invasive Urothelial Carcinoma After Surgical Resection
• Date of first enrolment: October 5, 2015
• Target sample size: 809
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02450331
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Australia, Belarus, Belgium, Canada, China, Czech Republic, Czechia, Finland, France, Germany, Greece, Israel, Italy, Japan, Korea, Republic of, Netherlands, Poland, Russian Federation, Serbia, Spain, Switzerland, Taiwan, Turkey, Ukraine, United Kingdom, United States

Contacts

• Name: Clinical Trials
• Affiliation: Hoffmann-La Roche

Key inclusion & exclusion criteria

Inclusion Criteria:

- Histologically confirmed muscle-invasive UC (also termed transitional cell carcinoma)
of the bladder or upper urinary tract (i.e., renal pelvis or ureters)

- For participants treated with prior neoadjuvant chemotherapy: tumor stage of ypT2-4a
or ypN+ (ypT2-4 or ypN+ for participants with upper urinary tract UC) and M0

- For participants who have not received prior neoadjuvant chemotherapy: tumor stage of
pT3-4a or pN+ (pT3-4 or pN+ for participants with upper urinary tract UC) and M0

- Representative formalin-fixed paraffin-embedded tumor specimens from surgical
resection (i.e., radical cystectomy, nephroureterectomy, or lymph node dissection) in
paraffin blocks (blocks preferred) or at least 15 unstained slides, with an associated
pathology report, for central testing and determined to be evaluable for tumor
programmed death-ligand 1 (PD-L1) expression prior to study enrollment

- Absence of residual disease and absence of metastasis, as confirmed by a negative
baseline computed tomography (CT) or magnetic resonance imaging scan of the pelvis,
abdomen, and chest no more than 4 weeks prior to randomization

- Full recovery from cystectomy or nephroureterectomy within 14 weeks following surgery

- Eastern Cooperative Oncology Group performance status of less than or equal to (
- Life expectancy greater than or equal to (>/=) 12 weeks

- Adequate hematologic and end-organ function

- For women who are not postmenopausal or surgically sterile: agreement to remain
abstinent or use contraceptive methods that result in a failure rate of less than (<)
1 percent (%) per year during the treatment period and for at least 5 months after the
last dose of atezolizumab

Exclusion Criteria:

- Any approved anti-cancer therapy within 3 weeks prior to initiation of study treatment

- Adjuvant chemotherapy or radiation therapy for UC following surgical resection

- Treatment with any other investigational agent or participation in another clinical
trial with therapeutic intent within 28 days or five half-lives of the drug prior to
enrollment

- Malignancies other than UC within 5 years prior to Cycle 1, Day 1

- Pregnancy or breastfeeding

- Significant cardiovascular disease

- Severe infections within 4 weeks prior to Cycle 1, Day 1

- Major surgical procedure other than for diagnosis within 28 days prior to Cycle 1, Day
1

- History of severe allergic, anaphylactic, or other hypersensitivity reactions to
chimeric or humanized antibodies or fusion proteins

- Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells
or any component of the atezolizumab formulation

- History of autoimmune disease

- Prior allogeneic stem cell or solid organ transplant

- History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced
pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening
chest CT scan

- Positive test for human immunodeficiency virus and/or active hepatitis B or hepatitis
C or tuberculosis

- Administration of a live, attenuated vaccine within 4 weeks before Cycle 1 Day 1

- Prior treatment with cluster of differentiation 137 (CD137) agonists or immune
checkpoint blockade therapies, including anti-CD40, anti-cytotoxic
T-lymphocyte-associated protein 4 (anti-CTLA-4), anti-programmed death-1 (anti-PD-1),
and anti-PD-L1 therapeutic antibodies



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Carcinoma, Transitional Cell

Intervention(s)

Drug: Atezolizumab

Primary Outcome(s)

Disease-Free Survival (DFS), as Assessed by Investigator [Time Frame: Randomization up to first occurrence of DFS event (up to approximately 50 months)]

Secondary Outcome(s)

EuroQol 5-Dimension 5-Level (EQ-5D-5L) Visual Analogue Scale Score [Time Frame: Day 1 of Cycle 1 up to approximately 50 months (Cycle length = 21 days)]

Non-Urinary Tract Recurrence-Free Survival (NURFS) [Time Frame: Randomization up to time of first occurrence of a NURFS event (up to approximately 50 months)]

Maximum Observed Serum Atezolizumab Concentration (Cmax) [Time Frame: Day 1 of Cycle 1 (Cycle length = 21 days)]

Disease-Specific Survival (DSS), as Assessed by Investigator [Time Frame: Randomization until death due to UC (up to approximately 50 months)]

Distant Metastasis-Free Survival (DMFS) [Time Frame: Randomization up to diagnosis of distant metastases or death from any cause (up to approximately 50 months)]

Minimum Observed Serum Atezolizumab Concentration (Cmin) [Time Frame: Pre-dose (Hour 0) on Day 1 of Cycles 1, 2, 3, 4, every 8 cycles from Cycle 8, at treatment discontinuation, 120 days after treatment discontinuation (up to approximately 50 months))(Cycle length = 21 days)]

Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab [Time Frame: Baseline up to approximately 50 months]

Overall Survival (OS) [Time Frame: Randomization until death due to any cause (up to approximately 50 months)]

Percentage of Participants With Adverse Events (AEs) [Time Frame: Screening up to approximately 50 months]

Secondary ID(s)

2014-005603-25

WO29636

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 18/11/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02450331