A Phase 3, Multicenter, Multinational, Randomized, Open-Label, Parallel-Arm Study of Avelumab* (MSB0010718C) plus Best Supportive Care Versus Best Supportive Care Alone as a Maintenance Treatment in Patients with Locally Advanced or Metastatic Urothelial Cancer whose Disease did not Progress after Completion of First-Line Platinum-Containing Chemotherapy
- Conditions
- Urothelial cancer10038364
- Registration Number
- NL-OMON55699
- Lead Sponsor
- Pfizer
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 20
1. Histological diagnosis of confirmed, unresectable locally advanced or
metastatic transitional cell carcinoma of the urothelium. patients with
documented Stage IV disease (per American Joint Committee on
cancer/International Union for Cancer Control Tumor Node Metastasis (TNM)
system 7th edition) at the start of first-line chemotherapy and measurable
disease prior to the start of first-line chemotherapy by RECIST v1.1., 2. Prior
first-line chemotherapy must have consisted of at least 4 cycles and no more
than 6 cycles of gemcitabine + cisplatin and/or gemcitabine + carboplatin. No
other chemotherapy regimens are allowed in this study. The last dose of
first-line chemotherapy must have been recieved no less than 4 weeks, and no
more than 10 weeks, prior to randomization; , 3. Patients without progressive
disease as per RECIST v1.1 guidelines (ie, with an ongoing CR, PR, or SD)
following completion of 4 to 6 cycles of first-line chemotherapy. Eligibility
based on this criterion will be determined by investigator review of
pre-chemotherapy and post-chemotherapy radiological assessments (CT/MRI
scans);, 4. Provision of a recent formalin-fixed, paraffin-embedded (FFPE)
tumor tissue block (subsection thereof) from the most recent primary or
metastatic tumor biopsy or resection obtained prior to treatment with first
line chemotherapy but within 24 monthsof randomization, with no intervening
systemic anti-cancer therapy. If a FFPE tissue block cannot be provided 15
freshly cut unstained slides (10 minimum) will be acceptable. Tumor tissue from
cytologic sampling (eg, fine needle aspiration, including FFPE cell pellet
material) or bone metastases are not acceptable and should not be sumbitted;,
5. Evidence of a signed and dated informed consent document indicating that the
patient (or a legally acceptable representative, as allowed by local
guideline/practice) has been informed of all pertinent aspects of the study, ,
6. Patients who are willing and able to comply with scheduled visits, treatment
plans, laboratory tests, and other study procedures;, 7. Age above 18 years;,
8. Estimated life expectancy of at least 3 months; , 9. Eastern Cooperative
Oncology Group (ECOG) performance status (PS) 0 or 1; , 10. Adequate bone
marrow, renal and liver function; , 11. Negative serum pregnancy test at
screening (for females of childbearing potential); , 12. Female patients able
to have children must agree to use a highly effective method of contraception
throughout the study and for at least 30 days after the last dose of assigned
treatment.
1. Patients whose disease progressed by RECIST v1.1 on or after first-line
chemotherapy for urothelial cancer; , 2. Prior adjuvant or neoadjuvant
(systemic) therapy within 12 months of randomization; , 3. Prior immunotherapy
with IL-2, IFN-*, or an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or
CTLA-4 antibody (including ipilimumab), or any other antibody or drug
specifically targeting T-cell co-stimulation or immune checkpoint pathways;, 4.
Major surgery within 4 weeks or major radiation therapy within 2 weeks prior to
randomization. Prior palliative radiotherapy (<= 10 fractions) to metastatic
lesion(s) is permitted, provided it has been completed at least 48 hours prior
to patient randomization;, 5. Patients with known symptomatic central nervous
system (CNS) metastases requiring steroids. Patients with previously diagnosed
CNS metastases are eligible if they have completed their treatment and have
recovered from the acute effects of radiation therapy or surgery prior to
randomization, have discontinued corticosteroid treatment for these metastases
for at least 4 weeks, and are neurologically stable;, 6. Persisting toxicity
related to prior therapy NCI CTCAE v4.0 Grade >1; however, alopecia, sensory
neuropathy Grade <= 2 is acceptable, or other grade <= adverse events not
constituting a sefetey risk based on the investigator's judgement are
acceptable;, 7. Diagnosis of any other malignancy within 5 years prior to
randomization, except for adequately treated basal cell or squamous cell skin
cancer, or carcinoma in situ of the breast or of the cervix, or low-grade
(Gleason 6 or below) prostate cancer on surveillance without any plans for
treatment intervention (eg, surgery, radiation, or castration), or prostate
cancer that had been adequatley treated with prostatectomy or radiotherapy and
currentley with no evidence of disease or symptoms;, 8. Participation in other
studies involving investigational drug(s) within 4 weeks prior to
randomization. Observational studies are permitted;, 9. Active autoimmune
disease that might deteriorate when receiving an, immunostimulatory agent.
Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid
disease not requiring immunosuppressive treatment are eligible;, 10.
Clinically significant (ie, active) cardiovascular disease; cerebral vascular
accident/stroke (<6 months prior to enrolment), myocardial infarction (<6months
prior to enrolment), unstable angina, congestive heart failure, or serious
cardiac arrhythmia requiring medication;
11. Active infection requiring systemic therapy;, 12. Known severe
hypersensitivity reactions to monoclonal antibodies (Grade >= 3), any
history of anaphylaxis, or uncontrolled asthma;, 13. Known prior or suspected
hypersensitivity to study drugs or any component in their formulations;, 14.
Current or prior use of immunosuppressive medication within 7 days prior to
randomization;, 15. Diagnosis of prior immunodeficiency or organ transplant
requiring immunosuppressive therapy. 16. Positive test for human
immunodeficiency virus (HIV) infection or know acquired immunodeficiency
syndrome (AIDS)
17. Hepatitis B virus (HBV) or hepatitis C virus (HCV) at screening;, 18.
Vaccination within 4 weeks of the first dose of study treatment and while on
trial is prohibited ex
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Overall Survival (OS).</p><br>
- Secondary Outcome Measures
Name Time Method