Study of MPDL3280A (ANTI PD-L1 ANTIBODY) in Patients with PD-L1-selected, High-risk Muscle-invasive Bladder Cancer after Surgery

• Register: EUCTR
• Last refreshed on: 24 August 2015
• Main ID: EUCTR2014-005603-25-ES
• Date of registration: 01/06/2015
• Prospective Registration: Yes
• Primary sponsor: Roche Farma, S.A., que representa en España a F. Hoffmann-La Roche Ltd.
• Public title: Study of MPDL3280A (ANTI PD-L1 ANTIBODY) in Patients with PD-L1-selected, High-risk Muscle-invasive Bladder Cancer after Surgery
• Scientific title: A PHASE III, OPEN-LABEL, MULTICENTER, RANDOMIZED STUDY OF MPDL3280A (ANTI-PD-L1 ANTIBODY) VERSUS OBSERVATION AS ADJUVANT THERAPY IN PATIENTS WITH PD-L1-SELECTED, HIGH RISK MUSCLE INVASIVE BLADDER CANCER AFTER CYSTECTOMY
• Date of first enrolment: 30/07/2015
• Target sample size: 440
• Recruitment status: Authorised-recruitment may be ongoing or finished
• 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

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, 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 or cytologically confirmed muscle-invasive transitional cell carcinoma (TCC) (also termed urothelial carcinoma [UC]) of the bladder (excluding TCC of renal pelvis, ureters, or urethra)
- Tumor Nodes Metastasis (TNM) classification at pathological examination of cystectomy specimen - For patients treated with prior neoadjuvant chemotherapy: tumor stage of ypT2-T4a or ypN+; For patients not treated with prior neoadjuvant chemotherapy: tumor stage of pT3-T4a or pN+
- Cystectomy with lymph node dissection
- MIBC with a PD-L1 immunohistochemistry (IHC) score of IC2/3 prospectively determined on the cystectomy 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 within 12 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 90 days after the last dose of study drug
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 264
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 176

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 cystectomy
- Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to enrollment
- Malignancies other than MIBC 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

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

Muscle-invasive bladder cancer
MedDRA version: 18.0 Level: LLT Classification code 10022877 Term: Invasive bladder cancer System Organ Class: 100000004864

Intervention(s)

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)

Secondary Objective: ? To evaluate the efficacy of adjuvant MPDL3280A treatment, as measured by overall survival (OS), disease-specific survival (DSS) and distant metastasis-free survival (DMFS)
? To evaluate the safety and tolerability of MPDL3280A in the adjuvant setting
? To evaluate the incidence of anti-therapeutic antibodies (ATAs) against MPDL3280A and to explore the potential relationship of the immunogenicity response with pharmacokinetics (PK), safety, and efficacy
? To characterize the pharmacokinetics of MPDL32820A
? To assess health status as measured by the EuroQol 5-dimension, 5-level version (EQ-5D-5L) questionnaire

Timepoint(s) of evaluation of this end point: Up to 6 years

Main Objective: To evaluate the efficacy of adjuvant MPDL3280A treatment in patients with programmed death ligand 1 (PD L1) selected muscle invasive bladder cancer (MIBC), as measured by disease-free survival (DFS)

Primary end point(s): Investigator-assessed DFS

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 MPDL3280A and potential correlation with PK, pharmacodynamic, safety, and efficacy parameters
7. Maximum observed serum MPDL3280A concentration (Cmax)
8. Minimum observed serum MPDL3280A concentration (Cmin)
9. EQ-5D-5L

Timepoint(s) of evaluation of this end point: 1-5. Up to 6 years
6. Day 1 of Cycles 1, 2, 3, 8 and every 8 cycles starting Cycle 8 until 120 days after the last dose of MDPL3280A and at treatment discontinuation visit
7. Day 1 of Cycle 1
8. Day 1 of Cycles 1, 2, 3, 8 and every 8 cycles starting Cycle 8 until 120 days after the last dose of MDPL3280A and at treatment discontinuation visit
9. Up to 6 years

Secondary ID(s)

WO29636

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd