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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

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ClinicalTrials.gov Identifier: NCT01282463
Recruitment Status : Completed
First Posted : January 25, 2011
Results First Posted : July 2, 2019
Last Update Posted : September 9, 2019
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Tracking Information
First Submitted Date  ICMJE January 21, 2011
First Posted Date  ICMJE January 25, 2011
Results First Submitted Date  ICMJE June 13, 2019
Results First Posted Date  ICMJE July 2, 2019
Last Update Posted Date September 9, 2019
Study Start Date  ICMJE April 2011
Actual Primary Completion Date February 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 13, 2019)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: January 21, 2011)
Progression-Free Survival (PFS) [ Time Frame: 26 Months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 13, 2019)
  • Percentage of Participants Achieving Objective Response Rate (ORR) [ Time Frame: Randomization to Measured PD (Up to 40 Months) ]
    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.
  • Duration of Response [ Time Frame: First Criteria Met for CR or PR to Measured PD or Death From Any Cause (Up to 40 Months) ]
    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.
  • Number of Participants With Adverse Events (AEs) [ Time Frame: Up To 41.7 Months ]
    A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.
  • Pharmacokinetics (PK) Maximum Concentration (Cmax) Ramucirumab [ Time Frame: 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: Minimum Concentration (Cmin) Ramucirumab [ Time Frame: 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 ]
  • PK: Cmax Icrucumab [ Time Frame: Cycle 1:Predose,1 hr post-EOI, 48hr, 72hr Post-EOI; Cycle 3:Predose,EOI,1.5hr,24hr,48hr,72hr,168hr Post EOI ]
  • PK: Cmin Icrucumab [ Time Frame: Cycle 2:Predose,1hr post-EOI;Cycle 3:Predose,EOI,1.5hr,24hr,48hr,72hr,168hr Post EOI ]
  • Number of Participants With Serum Anti-Ramucirumab Antibody Assessment [ Time Frame: 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 ]
    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.
  • Number of Participants With Serum Anti-Icrucumab Antibody Assessment [ Time Frame: Cycle 1 Day 1 and Day 8 Predose and 1hr Post Dose ]
    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.
  • Pharmacodynamics (PD): Change in Circulating Levels of Placental Growth Factor (PlGF) [ Time Frame: 40 months ]
  • PD: Change in Circulating Levels of Vascular Endothelial Growth Factor-A (VEGF-A) [ Time Frame: 40 months ]
  • PD: Change in Circulating Levels of Vascular Endothelial Growth Factor-B (VEGF-B) [ Time Frame: 40 months ]
  • PD: Change in Circulating Levels of Soluble Vascular Endothelial Growth Factor-1 (VEGFR-1) [ Time Frame: 40 months ]
  • PD: Change in Circulating Levels of Soluble Vascular Endothelial Growth Factor-2 (VEGFR-2) [ Time Frame: 40 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: January 21, 2011)
  • Objective response rate (ORR) [ Time Frame: 26 Months ]
  • Duration of response [ Time Frame: 26 Months ]
  • Number of Participants With Adverse Events (AEs) [ Time Frame: 26 Months ]
  • Maximum concentration (Cmax) [ Time Frame: 26 Months ]
  • Minimum concentration (Cmin) [ Time Frame: 26 Months ]
  • Change in circulating levels of placental growth factor (PIGF) [ Time Frame: 26 Months ]
  • Change in circulating levels of vascular endothelial growth factor-A (VEGF-A) [ Time Frame: 26 Months ]
  • Change in circulating levels of vascular endothelial growth factor-B (VEGF-B) [ Time Frame: 26 Months ]
  • Change in circulating levels of soluble vascular endothelial growth factor-1 (VEGFR-1) [ Time Frame: 26 Months ]
  • Change in circulating levels of soluble vascular endothelial growth factor-2 (VEGFR-2) [ Time Frame: 26 Months ]
  • Serum Anti-Ramucirumab Antibody Assessment [ Time Frame: 26 Months ]
  • Serum Anti-18F1 Antibody Assessment [ Time Frame: 26 Months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Carcinoma of Urinary Tract
  • Urethral Carcinoma
  • Carcinoma of Ureter
  • Carcinoma of Renal Pelvis
Intervention  ICMJE
  • Drug: Docetaxel
    Docetaxel: 75 milligram/square meter (mg/m2) on Day 1 of each 21-day cycle
  • Biological: Ramucirumab DP
    Ramucirumab (DP): 10 milligram/kilogram (mg/kg) intravenous (IV) on day 1 of each 21-day cycle
    Other Names:
    • IMC-1121B
    • LY3009806
  • Biological: Icrucumab
    12 mg/kg I.V. on day 1 and Day 8 of each 21-day cycle
    Other Names:
    • IMC-18F1
    • LY3012212
Study Arms  ICMJE
  • Active Comparator: Docetaxel
    Cycles repeat every 3 weeks until disease Progression, unacceptable toxicity, or withdrawal.
    Intervention: Drug: Docetaxel
  • Experimental: Docetaxel + Ramucirumab DP
    Cycles repeat every 3 weeks until disease Progression, unacceptable toxicity, or withdrawal.
    Interventions:
    • Drug: Docetaxel
    • Biological: Ramucirumab DP
  • Experimental: Docetaxel + Icrucumab
    Cycles repeat every 3 weeks until disease Progression, unacceptable toxicity, or withdrawal.
    Interventions:
    • Drug: Docetaxel
    • Biological: Icrucumab
Publications * Petrylak DP, Tagawa ST, Kohli M, Eisen A, Canil C, Sridhar SS, Spira A, Yu EY, Burke JM, Shaffer D, Pan CX, Kim JJ, Aragon-Ching JB, Quinn DI, Vogelzang NJ, Tang S, Zhang H, Cavanaugh CT, Gao L, Kauh JS, Walgren RA, Chi KN. Docetaxel As Monotherapy or Combined With Ramucirumab or Icrucumab in Second-Line Treatment for Locally Advanced or Metastatic Urothelial Carcinoma: An Open-Label, Three-Arm, Randomized Controlled Phase II Trial. J Clin Oncol. 2016 May 1;34(13):1500-9. doi: 10.1200/JCO.2015.65.0218. Epub 2016 Feb 29.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 22, 2015)
148
Original Estimated Enrollment  ICMJE
 (submitted: January 21, 2011)
138
Actual Study Completion Date  ICMJE March 2015
Actual Primary Completion Date February 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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:

    • cirrhosis at a level of Child-Pugh B (or worse)
    • cirrhosis (any degree) and a history of hepatic encephalopathy or ascites resulting from cirrhosis and requiring ongoing treatment with diuretics and/or paracentesis
  • If female, is surgically sterile, postmenopausal, or compliant with a highly effective contraceptive method during and for 12 weeks after the treatment period
  • If male, the patient is surgically sterile or compliant with a contraceptive regimen during and for 12 weeks after the treatment period

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
  • Has known human immunodeficiency virus infection or acquired immunodeficiency syndrome
  • Has received a prior autologous or allogeneic organ or tissue transplantation
  • Received chemotherapy within 21 days prior to randomization; and/or is currently enrolled in, or discontinued within 21 days prior to randomization from, a clinical trial involving an investigational product or unapproved use of a drug or device (other than the study drug[s] used in this study), or is concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study; and/or was treated with anti-angiogenic therapy within 28 days prior to randomization
  • Has undergone major surgery within 28 days prior to randomization, or subcutaneous venous access device placement within 7 days prior to randomization
  • Has had a serious nonhealing wound, ulcer, or bone fracture within 28 days prior to randomization
  • Has an elective or planned major surgery to be performed during the course of the trial
  • Is pregnant or lactating
  • Has a concurrent active malignancy other than adequately treated non-melanomatous skin cancer, curatively treated cervical carcinoma in-situ, other noninvasive carcinoma or in-situ neoplasm, or prostate cancer with an undetectable prostate specific antigen (PSA) and no current treatment with hormone therapy
  • Has an acute/subacute bowel obstruction or history of chronic diarrhea requiring ongoing medical intervention
  • History of gastrointestinal perforation and/or fistula within 6 months prior to randomization
  • Has active diverticulitis
  • Known hypersensitivity to docetaxel or other drugs formulated with polysorbate 80
  • Known hypersensitivity to agents of similar biologic composition as ramucirumab DP, IMC-18F1, or other agents that specifically target vascular endothelial growth factor receptor (VEGF)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01282463
Other Study ID Numbers  ICMJE 13943
CP20-0902 ( Other Identifier: ImClone Systems )
I4Y-IE-JCDC ( Other Identifier: Eli Lilly and Company )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: 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.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
URL: https://vivli.org/
Responsible Party Eli Lilly and Company
Study Sponsor  ICMJE Eli Lilly and Company
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: 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) Eli Lilly and Company
PRS Account Eli Lilly and Company
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP