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
Condition: Carcinoma of Urinary Tract; Urethral Carcinoma; Carcinoma of Ureter; Carcinoma of Renal Pelvis
MeSH terms: Carcinoma
Intervention: Docetaxel; Ramucirumab DP; Icrucumab
Intervention description: 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; 12 mg/kg I.V. on day 1 and Day 8 of each 21-day cycle
Intervention MeSH terms: Docetaxel; Ramucirumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 148.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Carcinoma, Renal Cell

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.
    

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:

               -  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)