Study of Atezolizumab (ANTI PD-L1 ANTIBODY) in Patients with PD-L1-selected, High-risk Muscle-invasive Urothelial Carcinoma after Surgical Resection

• Register: EUCTR
• Last refreshed on: 2 May 2022
• Main ID: EUCTR2014-005603-25-FI
• Date of registration: 08/06/2015
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd
• Public title: Study of Atezolizumab (ANTI PD-L1 ANTIBODY) in Patients with PD-L1-selected, High-risk Muscle-invasive Urothelial Carcinoma after Surgical Resection
• Scientific title: A PHASE III, OPEN-LABEL, MULTICENTER, RANDOMIZED STUDY OF ATEZOLIZUMAB VERSUS OBSERVATION AS ADJUVANT THERAPY IN PATIENTS WITH PD-L1-SELECTED, HIGH RISK MUSCLE INVASIVE UROTHELIAL CARCINOMA AFTER SURGICAL RESECTION
• Date of first enrolment: 07/08/2015
• Target sample size: 800
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-005603-25
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Observation Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

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

Contacts

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
- Age >=18 years
- Histologically confirmed muscle-invasive UC (also termed transitional cell carcinoma [TCC]) of the bladder or upper urinary tract (i.e., renal pelvis or ureters)
- Patients with upper urinary tract urothelial carcinoma (UTUC) will be limited to no more than approximately 10% of the study population
- Tumor Nodes Metastasis (TNM) classification at pathological examination of surgical resection - For patients treated with prior neoadjuvant chemotherapy: tumor stage of ypT2-4a or ypN+ (yp T2-4 or ypN+ for patients with UTUC); For patients not treated with prior neoadjuvant chemotherapy: tumor stage of pT3-T4a or pN+ (pT3-4 or pN+ for patients with UTUC)
- Surgical resection of muscle-invasive UC of the bladder, or upper urinary tract
- Muscle-invasive UC with programmed death ligand 1(PD-L1) expression per immunohistochemistry (IHC) prospectively determined on hte surgical resection or lymph node dissection tumor specimens by a central laboratory
- Absence of residual disease and absence of metastasis, as confirmed by a negative baseline computed tomography (CT) or magnetic resonance imaging (MRI) scan of the pelvis, abdomen, and chest no more than 6 weeks prior to randomization
- Full recovery from cystectomy or nephroureterectomy within 14 weeks following surgery
- Eastern Cooperative Oncology Group performance status score of <=2
- Life expectancy >=12 weeks
- Adequate hematologic and end-organ function
- For women who are not postmenopausal (>=12 months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use single or combined non-hormonal contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 5 months after the last dose of atezolizumab, and agreement to refrain from donating eggs during this same period

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 352
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 448

Exclusion criteria:
- Any approved anti-cancer therapy, including chemotherapy, or hormonal 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 prior to enrollment
- Malignancies other than UC within 5 years prior to Cycle 1, Day 1
- History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
- History of autoimmune disease
- History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
- Tested Positive for HIV
- Patients with active hepatitis B virus and tuberculosis
- Prior allogeneic stem cell or solid organ transplant
- Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within the previous 3 months, unstable arrhythmias, or unstable angina
- Major surgical procedure other than for diagnosis within 28 days prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure during the course of the study
- Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CD40, anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Muscle-invasive urothelial carcinoma
MedDRA version: 20.0 Level: LLT Classification code 10022877 Term: Invasive bladder cancer System Organ Class: 100000004864

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Trade Name: Tecentriq
Product Code: MPDL3280A-RO5541267
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Not yet defined
Current Sponsor code: RO5541267
Other descriptive name: MPDL3280A
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 60-

Primary Outcome(s)

Main Objective: To evaluate the efficacy of adjuvant Atezolizumab treatment in patients with muscle-invasive urothelial carcinoma (UC) as measured by disease-free survival (DFS)

Timepoint(s) of evaluation of this end point: Up to 7 years

Primary end point(s): Investigator-assessed DFS

Secondary Objective: • To evaluate the efficacy of adjuvant atezolizumab treatment, as measured by overall survival (OS), disease-specific survival (DSS) and distant metastasis-free survival (DMFS) and non-urinary tract recurrence-free survival (NURFS)
• To evaluate the safety and tolerability of atezolizumab in the adjuvant setting
• To evaluate the incidence of anti-therapeutic antibodies (ATAs) against atezolizumab and to explore the potential relationship of the immunogenicity response with pharmacokinetics (PK), safety, and efficacy
• To characterize the pharmacokinetics of atezolizumab
• To assess health status as measured by the EuroQol 5-dimension, 5-level version (EQ-5D-5L) questionnaire

Secondary Outcome(s)

Secondary end point(s): 1. OS
2. DSS
3. DMFS
4. Incidence of adverse events
5. Changes in vital signs and clinical laboratory results
6. Incidence of ATA response to atezolizumab and potential correlation with PK, pharmacodynamic, safety, and efficacy parameters
7. Maximum observed serum atezolizumab concentration (Cmax)
8. Minimum observed serum atezolizumab concentration (Cmin)
9. EQ-5D-5L
10. NURFS

Timepoint(s) of evaluation of this end point: 1-5. Up to 7 years
6. Day 1 of Cycles 1, 2, 3, 4 and every 8 cycles starting Cycle 8 until 120 days after the last dose of atezolizumab and at treatment discontinuation visit
7. Day 1 of Cycle 1
8. Day 1 of Cycles 1, 2, 3, 4 and every 8 cycles starting Cycle 8 until 120 days after the last dose of atezolizumab and at treatment discontinuation visit
9-10. Up to 7 years

Secondary ID(s)

WO29636

2014-005603-25-ES

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd

Ethics review

Status: Approved
Approval date: 16/06/2015
Contact:

Results

• Results available: Yes
• Date Posted: 06/11/2020
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-005603-25/results