Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Symptoms and General Pathology

Rare Diseases

Carcinoma

Urinary Bladder Neoplasms

Carcinoma, Renal Cell

Carcinoma, Transitional Cell

Disease Progression

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Transitional Cell Carcinoma

Urethral Cancer

Antineoplastic Agents

All Drugs and Chemicals

Docetaxel

Ramucirumab

Tubulin Modulators

Antimitotic Agents

Angiogenesis Inhibitors

Growth Inhibitors

Cycles repeat every 3 weeks until disease Progression, unacceptable toxicity, or withdrawal.

Docetaxel: 75 milligram/square meter (mg/m2) on Day 1 of each 21-day cycle

Ramucirumab (DP): 10 milligram/kilogram (mg/kg) intravenous (IV) on day 1 of each 21-day cycle

Ramucirumab DP

12 mg/kg I.V. on day 1 and Day 8 of each 21-day cycle

Icrucumab

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

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.

Study of Ramucirumab or Icrucumab (IMC-18F1) With Docetaxel or Docetaxel Alone as Second-Line Therapy in Participants With Bladder,Urethra, Ureter, or Renal Pelvis Carcinoma

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

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

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.

Participants achieved an objective response if they had a best overall response of partial response (PR) or complete response (CR). According to RECIST v1.1, PR was defined as at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph node), taking as reference the baseline sum diameter; CR was the disappearance of all non-nodal target lesions, with the short axes of any target lymph node reduced to \<10 mm, the disappearance of all nontarget lesions, and the normalization of tumor marker levels \[if tumor markers were initially above the upper limit of normal (ULN)\]. The percentage of participants who achieved an objective response=(number of participants with CR or PR)/(number of participants assessed)\*100.

The duration of response was measured from the time measurement criteria were first met for a CR or PR (whichever was first recorded) until the first date of objectively documented progressive disease (taking as a reference for progressive disease the smallest measurement recorded since randomization) or the date of death, whichever occurred first. Data for participants who did not relapse or die were censored at the day of their last adequate tumor assessment. Duration of response was estimated by the Kaplan-Meier method.

A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.

Number of participants with at least one positive titer treatment emergent antibody positive neutralizing antibody detecting. A sample will be considered positive for anti-Ramucirumab antibodies if it exhibits a post-baseline antibody level exceeding the normal anti-Ramucirumab antibody level seen in healthy untreated individuals.

A sample will be considered positive for anti-Icrucumab antibodies if it exhibits a post-baseline antibody level exceeding the normal anti-IMC-Icrucumab antibody level seen in healthy untreated individuals.

Eli Lilly and Company

All randomized participants who received at least one dose of study drug.

Cycles repeat every 3 weeks until disease Progression, unacceptable toxicity, or withdrawal.

Docetaxel: Docetaxel: 75 mg/m2 on Day 1 of each 21-day cycle

Cycles repeat every 3 weeks until disease Progression, unacceptable toxicity, or withdrawal.

Docetaxel: Docetaxel: 75 mg/m2 on Day 1 of each 21-day cycle

Ramucirumab DP: Ramucirumab (DP): 10 mg/kg IV on day 1 of each 21-day cycle

Docetaxel + Ramucirumab DP

Cycles repeat every 3 weeks until disease Progression, unacceptable toxicity, or withdrawal.

Docetaxel: Docetaxel: 75 mg/m2 on Day 1 of each 21-day cycle

Icrucumab: 12 mg/kg IV on day 1 and Day 8 of each 21-day cycle

Docetaxel + Icrucumab

Cycles repeat every 3 weeks until disease Progression, unacceptable toxicity, or withdrawal.

Docetaxel: 75 mg/m2 on Day 1 of each 21-day cycle

Cycles repeat every 3 weeks until disease Progression, unacceptable toxicity, or withdrawal.

Docetaxel: 75 mg/m2 on Day 1 of each 21-day cycle

Ramucirumab (DP): 10 mg/kg IV on day 1 of each 21-day cycle

Cycles repeat every 3 weeks until disease Progression, unacceptable toxicity, or withdrawal.

Docetaxel: 75 mg/m2 on Day 1 of each 21-day cycle

Icrucumab: 12 mg/kg IV on day 1 and Day 8 of each 21-day cycle

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Canada

United States

Region of Enrollment

All randomized participants who received at least 1 dose of study drug.

Chief Medical Officer

All randomized participants who received at least one dose of study drug. Participants censored: docetaxel arm = 40; docetaxel and ramucirumab arm = 34; docetaxel and Icrucumab arm = 41.

Progression-Free Survival (PFS)

All randomized participants who received one dose of study drug.

Percentage of Participants Achieving Objective Response Rate (ORR)

All randomized participants received one dose of study drug and had CR or PR.

Duration of Response

Any AE

Any SAE

Number of Participants With Adverse Events (AEs)

Cycle 1

Cycle 2

Cycle 3

Cycle 4

Cycle 6

All randomized participants who received at least one dose of study drug and had evaluable PK data for Ramucirumab and there was no PK data for Docetaxel arm.

Pharmacokinetics (PK) Maximum Concentration (Cmax) Ramucirumab

PK: Minimum Concentration (Cmin) Ramucirumab

Cycle 1 Cmax

Cycle 3 Cmax

Cycles repeat every 3 weeks until disease Progression, unacceptable toxicity, or withdrawal.

Docetaxel: 75 mg/m2 on Day 1 of each 21-day cycle

Icrucumab: 12 mg/kg IV on Day 1 and Day 8 of each 21-day cycle

All randomized participants who received at least one dose of study drug and had evaluable PK data for Icrucumab and there was no PK data for Docetaxel arm.

PK: Cmax Icrucumab

Day 1 Cycle 2

Day 1 Cycle 3

PK: Cmin Icrucumab

All randomized participants who received at least one dose of study drug and had baseline and post baseline anti-ramucirumab antibodies.

Number of Participants With Serum Anti-Ramucirumab Antibody Assessment

Zero participants analyzed. Data not collected.

Number of Participants With Serum Anti-Icrucumab Antibody Assessment

Pharmacodynamics (PD): Change in Circulating Levels of Placental Growth Factor (PlGF)

PD: Change in Circulating Levels of Vascular Endothelial Growth Factor-A (VEGF-A)

Cycles repeat every 3 weeks until disease Progression, unacceptable toxicity, or withdrawal.

Docetaxel: Docetaxel: 75 milligram/square meter (mg/m2) on Day 1 of each 21-day cycle

PD: Change in Circulating Levels of Vascular Endothelial Growth Factor-B (VEGF-B)

PD: Change in Circulating Levels of Soluble Vascular Endothelial Growth Factor-1 (VEGFR-1)

PD: Change in Circulating Levels of Soluble Vascular Endothelial Growth Factor-2 (VEGFR-2)

Cycles repeat every 3 weeks until disease Progression, unacceptable toxicity, or withdrawal.

Docetaxel: 75 milligram/square meter (mg/m2) on Day 1 of each 21-day cycle

Spots Global Cancer Trial Database for carcinoma of ureter