An Open-Label, Multicenter, Randomized Phase 2 Study Evaluating the Safety and Efficacy of Docetaxel in Combination With Ramucirumab (IMC-1121B) Drug Product or IMC-18F1 or Without Investigational Therapy as Second-line Therapy in Patients With Locally Advanced or Metastatic Transitional Cell Carcinoma of the Bladder, Urethra, Ureter, or Renal Pelvis Following Disease Progression on First-line Platinum-based Therapy
Overview
- Phase
- Phase 2
- Intervention
- Docetaxel
- Conditions
- Carcinoma of Urinary Tract
- Sponsor
- Eli Lilly and Company
- Enrollment
- 148
- Locations
- 1
- Primary Endpoint
- Progression-Free Survival (PFS)
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
This multicenter trial will enroll participants with metastatic transitional cell carcinoma of the bladder, urethra, ureter, or renal pelvis who have had disease progression on first-line platinum-based chemotherapy regimens. Participants will be enrolled into 1 of 3 treatment arms: docetaxel; docetaxel and ramucirumab; or docetaxel and icrucumab.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically confirmed transitional cell carcinoma of the bladder, urethra, ureter, or renal pelvis
- •Locally advanced or metastatic and unresectable transitional cell carcinoma of the bladder, urethra, ureter, or renal pelvis
- •Had treatment with a platinum-containing regimen
- •Disease progression within 12 months of after receiving the last dose of a platinum containing regimen in the neoadjuvant or adjuvant setting, and/or had disease progression while on a platinum-containing regimen or within 12 months after the last dose of therapy in the locally advanced or metastatic setting
- •Has measurable or nonmeasurable disease
- •Life expectancy of ≥ 3 months
- •Received no more than 2 prior systemic chemotherapy regimens in any setting
- •Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- •Has adequate hematologic, coagulation, hepatic and renal function
- •Does not have:
Exclusion Criteria
- •Received more than one prior systemic treatment regimen for metastatic disease
- •Received prior systemic taxane therapy (except for prior paclitaxel therapy) for Transitional Cell Carcinoma of the bladder, urethra, ureter, or renal pelvis in any setting (neoadjuvant, adjuvant, metastatic). Prior intravesical taxane therapy is allowed
- •Has received more than one prior anti-angiogenic agent for Transitional Cell Carcinoma of the bladder, urethra, ureter, or renal pelvis
- •Has received radiation therapy within 4 weeks prior to randomization
- •Has a history of uncontrolled hereditary or acquired bleeding or thrombotic disorders
- •Has experienced a Grade ≥ 3 bleeding event (eg, via gastric ulcers, gastric varices, or gross hematuria) within 3 months prior to randomization
- •Has uncontrolled intercurrent illness including, but not limited to symptomatic anemia, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, psychiatric illness/social situations, or any other serious uncontrolled medical disorders
- •Has experienced any arterial thrombotic or thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack or cerebrovascular accident, within 6 months prior to randomization
- •Has known brain metastases, uncontrolled spinal cord compression, or leptomeningeal disease
- •Has an ongoing or active infection requiring parenteral antibiotic, antifungal, or antiviral therapy
Arms & Interventions
Docetaxel
Cycles repeat every 3 weeks until disease Progression, unacceptable toxicity, or withdrawal.
Intervention: Docetaxel
Docetaxel + Ramucirumab DP
Cycles repeat every 3 weeks until disease Progression, unacceptable toxicity, or withdrawal.
Intervention: Docetaxel
Docetaxel + Ramucirumab DP
Cycles repeat every 3 weeks until disease Progression, unacceptable toxicity, or withdrawal.
Intervention: Ramucirumab DP
Docetaxel + Icrucumab
Cycles repeat every 3 weeks until disease Progression, unacceptable toxicity, or withdrawal.
Intervention: Docetaxel
Docetaxel + Icrucumab
Cycles repeat every 3 weeks until disease Progression, unacceptable toxicity, or withdrawal.
Intervention: Icrucumab
Outcomes
Primary Outcomes
Progression-Free Survival (PFS)
Time Frame: Randomization to Measured PD or Death From Any Cause (Up To 40 Months)
PFS time was the time from randomization until the date of objectively determined progressive disease (PD) or death due to any cause, whichever occurred first. According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), PD was at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. In addition to the 20% relative increase, the sum must have also demonstrated an absolute increase of at least 5 millimeters (mm). The appearance of 1 or more new lesions and/or unequivocal progression of existing nontarget lesions was also considered progression. Participants without objectively determined PD who were alive at the end of the follow-up period (or lost to follow-up) were censored on the date of the participant's last complete radiographic tumor assessment; if no baseline or post-baseline radiologic assessment was available, the participant was censored at the date of randomization.
Secondary Outcomes
- Duration of Response(First Criteria Met for CR or PR to Measured PD or Death From Any Cause (Up to 40 Months))
- PK: Cmin Icrucumab(Cycle 2:Predose,1hr post-EOI;Cycle 3:Predose,EOI,1.5hr,24hr,48hr,72hr,168hr Post EOI)
- Number of Participants With Serum Anti-Icrucumab Antibody Assessment(Cycle 1 Day 1 and Day 8 Predose and 1hr Post Dose)
- PD: Change in Circulating Levels of Vascular Endothelial Growth Factor-B (VEGF-B)(40 months)
- PD: Change in Circulating Levels of Soluble Vascular Endothelial Growth Factor-2 (VEGFR-2)(40 months)
- Pharmacokinetics (PK) Maximum Concentration (Cmax) Ramucirumab(Cycle 1:Predose,1 hour(hr) post End of Infusion (EOI),48hr,72hr,168hr,336hr post-EOI;Cycle2:Predose,1hr post-EOI; Cycle3:Predose,1hr,48hr,72hr,168hr,336hr post-EOI; Cycle4:Predose,1hr post-EOI;Cycle6 and every other cycle thereafter:Predose,1hr Post EOI)
- PK: Cmax Icrucumab(Cycle 1:Predose,1 hr post-EOI, 48hr, 72hr Post-EOI; Cycle 3:Predose,EOI,1.5hr,24hr,48hr,72hr,168hr Post EOI)
- Pharmacodynamics (PD): Change in Circulating Levels of Placental Growth Factor (PlGF)(40 months)
- Number of Participants With Adverse Events (AEs)(Up To 41.7 Months)
- PK: Minimum Concentration (Cmin) Ramucirumab(Cycle 2:Predose,1hr post-EOI;Cycle3:Predose,1hr,48hr,72hr,168hr,336hr, post-EOI;Cycle4:Predose,1hr post-EOI;Cycle6:Predose,1hr Post EOI)
- Percentage of Participants Achieving Objective Response Rate (ORR)(Randomization to Measured PD (Up to 40 Months))
- Number of Participants With Serum Anti-Ramucirumab Antibody Assessment(Cycle 1:Predose,EOI,1hr,48hr,72hr,168hr,336 hr post-EOI:Cycle 2:Predose,1hr post-EOI;Cycle 3:Predose,1hr,48hr,72hr,168hr,336hr post-EOI;Cycle 4:Predose,1hr post-EOI;Cycle 6:Predose,1hr post-EOI)
- PD: Change in Circulating Levels of Vascular Endothelial Growth Factor-A (VEGF-A)(40 months)
- PD: Change in Circulating Levels of Soluble Vascular Endothelial Growth Factor-1 (VEGFR-1)(40 months)