Efficacy ObjectivesThe primary efficacy objective for this study is as follows:• To evaluate the efficacy of adjuvant atezolizumab treatment in patients with PD- L1*selected muscle invasive urothelial cancer, as measured by disease-free survival (…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
Hoog risico, spier geinvaseerde urotheelkanker.
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Efficacy Outcome Measures
The primary efficacy outcome measure for this study is as follows:
Investigator-assessed DFS, defined as the time from randomization to the time
of first occurrence of a DFS event, defined as any of the following:
Local (pelvic) recurrence of UC
Upper urinary tract or urethral recurrence of UC
Distant metastasis of UC
Death from any cause
Secondary outcome
The secondary efficacy outcome measures for this study are as follows:
• OS, defined as the time from randomization to the date of death from any cause
• DSS, defined as the time from randomization to the date of death from UC per
investigator assessment of cause of death
• DMFS, defined as the time from randomization to the date of diagnosis of
distant (i.e., non-locoregional) metastases or death from any cause
For Safety Outcome Measures. Pharmacokinetic Outcome Measures, Patient-Reported
Outcome Measures and Exploratory Outcome Measures see paragraph 3.4.2, 3.4.3,
3.4.4 and 3.4.5 of the protocol
Background summary
Atezolizumab is a human Ig G1 monoclonal antibody consisting of two heavy
chains (448 amino acids) and two light chains (214 amino acids) and is produced
in Chinese hamster ovary cells. Atezolizumab was engineered to eliminate
Fc-effector function via a single amino acid substitution at position 298 on
the heavy chain, which results in a non-glycosylated antibody that has minimal
binding to Fc receptors and prevents Fc-effector function at expected
concentrations in humans. Atezolizumab targets human PD-L1 and inhibits its
interaction with its receptors,PD-1 and B7.1 (CD80, B7-1). Both of these
interactions are reported to provide inhibitory signals to T cells.
Study objective
Efficacy Objectives
The primary efficacy objective for this study is as follows:
• To evaluate the efficacy of adjuvant atezolizumab treatment in patients with
PD- L1*selected muscle invasive urothelial cancer, as measured by disease-free
survival (DFS)
The secondary efficacy objectives for this study are as follows:
• To evaluate the efficacy of adjuvant atezolizumab treatment, as measured by
overall survival (OS)
• To evaluate the efficacy of adjuvant atezolizumabtreatment, as measured by
disease-specific survival (DSS)
• To evaluate the efficacy of adjuvant atezolizumabtreatment, as measured by
distant metastasis-free survival (DMFS)
For the other objectives of the study please see paragraph 2. of the protocol.
Study design
Study WO29636 is a global Phase III, open-label, randomized, controlled trial
designed to evaluate the efficacy and safety of adjuvant treatment
withatezolizumab compared with observation in patients with PD-L1-selected
urothelial cancrcinoma who are at high risk for recurrence following surgical
resection.
Patients who have received prior neoadjuvant chemotherapy are eligible, but
must have tumor staging of ypT2*4a or ypN+ at pathological examination of the
cystectomy specimen. Patients who have not received prior neoadjuvant
chemotherapy must be ineligible for or declined treatment with cisplatin-based
adjuvant chemotherapy and have tumor staging of pT3*4a or pN+.
Cystectomy tumor specimens from patients meeting eligibility criteria will be
evaluated for PD-L1 expression by IHC.
.
Patients will be randomized to one of the following arms in a 1:1 ratio:
• Arm A (experimental arm): atezolizumab1200 mg q3w
• Arm B (control arm): Observation
For more information, see page 24 and 25 in the protocol.
Intervention
The dose level of atezolizumab to be tested in this study is 1200 mg
(equivalent to an average body weight*based dose of 15 mg/kg) administered by
IV infusion every 3 weeks (21 [± 3] days) for 16 cycles or 1 year (whichever
occurs first).
Study burden and risks
The subject may get side effects from the drugs or procedures used in this
study. Side effects can range from mild to severe and can vary from person to
person. In some cases, side effects can be severe, long persisting or never
disappear. There is also a very small risk of death.
SIDE EFFECTS RELATED ATEZOLIZUMAB TREATMENT
The subject may experience the side effects described below. It is also
possible that side effects occur, which are not yet known at this time. As with
any experimental drug, atezolizumab may cause unknown and potentially serious
or life-threatening side effects.
The following adverse reactions are believed to be related to
atezolizumab:
• Inflammation of the thyroid and adrenal glands (hypothyroidism,
hyperthyroidism, or adrenal insufficiency)
• Hepatitis (inflammation of the liver)
• Pneumonitis (inflammation of the lungs)
• skin reactions (rash, itching, dry skin, redness and changes in skin
pigmentation)
• Flu-like illness (symptoms include fever, fatigue, asthenia [lack of energy],
chills, myalgia [muscle pain], arthralgia [joint pain] and headache).
• Reactions associated with infusion (adverse events occurred during infusion
or within 1 day of infusion and include fever, chills, dyspnea and flushing).
• Colitis (inflammation of the intestines).
• Meningitis (inflammation of the membrane around the spinal cord and brain).
• Neuropathies (damage to the nerves).
The adverse reactions observed when atezolizumab is administered solely, are
described in the protocol as well as the risks of other study procedures.
Beneluxlaan 2a
Woerden 3446 GR
NL
Beneluxlaan 2a
Woerden 3446 GR
NL
Listed location countries
Age
Inclusion criteria
• Histologically confirmed muscle-invasive UC (also termed TCC) of the bladder or upper
urinary tract (i.e., renal pelvis or ureters)
Patients with mixed histologies are required to have a dominant transitional cell pattern.
• TNM classification (UICC/AJCC 7th edition) at pathological examination of surgical
resection specimen as follows:
For patients treated with prior neoadjuvant chemotherapy: tumor stage of ypT2 -4a or
ypN+ (ypT2-4 or ypN+ for patients with UTUC)
For patients who have not received prior neoadjuvant chemotherapy: tumor stage of
pT3*4a or pN+ (pT3-4 or pN+ for patients with UTUC)
• Surgical resection of muscle-invasive UC of the bladder, or UTUC
Exclusion criteria
• 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, whichever is longer, prior to
enrollment
• 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
Patients who have received primary chemoradiation for bladder preservation before
cystectomy are eligible and will be treated as the same as patients who have received
prior neoadjuvant chemotherapy.
Postsurgical intrapelvic/intravesical chemotherapy or BCG is not allowed for patients
with UTUC.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-005603-25-NL |
| ClinicalTrials.gov | NCT02450331 |
| CCMO | NL53644.031.15 |