A Phase 3, Open-label, Randomized Study of Nivolumab Combined with Ipilimumab, or with Standard of Care Chemotherapy, versus Standard of Care Chemotherapy in participants with Previously Untreated Unresectable or Metastatic Urothelial Cancer
- Conditions
- Bladder CancerUrothelial Carcinoma10004994
- Registration Number
- NL-OMON56458
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 70
• Histological or cytological evidence of metastatic or surgically unresectable
transitional cell carcinoma (TCC) of the urothelium involving the renal pelvis,
ureter, bladder or urethra. Minor histologic variants (< 50% overall) are
acceptable (TCC must be the dominant histology).
• Measurable disease by CT or MRI per RECIST 1.1 criteria.
• No prior systemic chemotherapy for metastatic or surgically unresectable UC
with the exception of prior intravesical therapy completed more than 4 weeks
prior to initiation of study treatment or prior neoadjuvant chemotherapy,
radiation or prior adjuvant platinum-based chemotherapy or radiation following
radical cystectomy with recurrence >= 12 months from completion of therapy.
• Cisplatin-ineligible participants will be defined by impaired renal function,
hearing loss or peripheral neuropathy
• Participants must provide a fresh tumor biopsy (<3 months) from the disease
site. If the primary site is not available (ie, radical cystectomy), a
fresh biopsy from a metastatic site should be submitted.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.
• Adequate hematologic and liver function
• Prior palliative radiotherapy must have been completed at least 2 weeks
prior to study drug
administration. Participants must have measurable disease outside the
radiation field to be
eligible and the tumor sample be collected before (but not after)
palliative RT if it is from
the irradiated area. Participants with progression in a previously
radiated field will also be
eligible.
• Disease that is suitable for local therapy administered with curative intent.
• Presence of active brain metastases or leptomeningeal metastases
• Patients who are HIV positive
• Patients who are hepatitis B or C positive
• Prior malignancy active within the previous 3 years except for locally
curable cancers
• Participants must have recovered from the effects of major surgery requiring
general anesthetic or significant traumatic injury at least 14 days before
randomization or treatment assignment.
• Uncontrolled adrenal insufficiency.
• Any other serious or uncontrolled medical disorder or illness that may
increase the risk associated with study participation or study drug
administration, impair the ability of the participant to receive protocol
therapy, or interfere with the interpretation of study results.
• Participants may not have received live/attenuated vaccines within 30 days
prior to first study treatment.
• Treatment with botanical preparations intended for general health support or
to treat the disease under study within 2 weeks prior to first study treatment.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>To compare Overall Survival (OS) of nivolumab combined with ipilimumab versus<br /><br>standard of care (SOC) chemotherapy in cisplatin-ineligible participants with<br /><br>previously untreated, unresectable or metastatic urothelial carcinoma (UC).<br /><br>Efficacy will be evaluated by Overall Survival in cisplatin-ineligible<br /><br>randomized participants.<br /><br><br /><br>To compare OS of nivolumab combined with ipilimumab versus standard of care<br /><br>(SOC) chemotherapy in PD-L1 positive (>= 1%) participants with previously<br /><br>untreated, unresectable or metastatic UC. Efficacy will be evaluated by Overall<br /><br>Survival in PD-L1 positive (>= 1%) randomized participants by<br /><br>immunohistochemistry.</p><br>
- Secondary Outcome Measures
Name Time Method <p>To compare OS of nivolumab combined with ipilimumab versus SOC chemotherapy in<br /><br>all randomized participants with previously untreated, unresectable or<br /><br>metastatic UC.<br /><br><br /><br>To evaluate Progression-Free Survival (PFS) of nivolumab combined with<br /><br>ipilimumab versus SOC chemotherapy in cisplatin-ineligible randomized<br /><br>participants, in PD-L1 positive (>=1%) randomized participants and in all<br /><br>randomized participants with previously untreated, unresectable or metastatic<br /><br>UC.<br /><br><br /><br>To evaluate changes from baseline in Health-Related QOL (HRQoL) of nivolumab<br /><br>combined with ipilimumab versus SOC chemotherapy in all randomized participants<br /><br>with previously untreated, unresectable or metastatic UC.</p><br>