A Study of Ramucirumab (LY3009806) Plus Docetaxel in Participants With Urothelial Cancer
Condition: Urothelial Carcinoma
MeSH terms: Carcinoma; Carcinoma, Transitional Cell
Intervention: Ramucirumab; Docetaxel; Placebo
Intervention description: Administered IV; Administered IV; Administered IV
Intervention MeSH terms: Docetaxel; Ramucirumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 530.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: carcinoma of the bladder; carcinoma of the urethra; carcinoma the of ureter; carcinoma of the renal pelvis; transitional cell carcinoma; transitional cell tumor; RANGE; bladder cancer

Summary:

      The main purpose of this study is to evaluate the safety and efficacy of the study drug
      ramucirumab in combination with docetaxel in participants with urothelial cancer who failed
      prior platinum-based therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Have histologically or cytologically confirmed, locally advanced or unresectable or
             metastatic urothelial (transitional cell) carcinoma of the bladder, urethra, ureter,
             or renal pelvis.

          -  Had disease progression while on a platinum containing regimen in the first-line
             setting or within 14 months after completing the first-line platinum regimen.
             Participants who received treatment with one immune checkpoint inhibitor regimen are
             eligible (for example Programmed death 1 (PD-1), Programmed death-ligand 1 (PDL1), or
             CTLA4) and may have a longer interval since prior platinum-containing therapy (≤24
             months).

          -  Have a life expectancy of ≥3 months.

          -  Have received no more than one prior systemic chemotherapy regimen in the relapsed or
             metastatic setting. Prior treatment with no more than one prior immune checkpoint
             inhibitor is permitted and will not be considered as a line of systemic chemotherapy.

          -  Have measurable disease or nonmeasurable but evaluable disease as defined by Response
             Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1).

          -  Have an Eastern Cooperative Oncology Group (ECOG) of 0 or 1.

          -  Have adequate hematologic function.

          -  Have adequate coagulation function.

          -  Have adequate hepatic function.

          -  The participant does not have:

               -  cirrhosis at a level of Child-Pugh B (or worse)

               -  cirrhosis (any degree) and a history of hepatic encephalopathy or clinically
                  meaningful ascites resulting from cirrhosis

          -  Have adequate renal function as defined by creatinine clearance >30
             milliliters/minute.

          -  Have urinary protein ≤1+ on dipstick or routine urinalysis.

          -  The participant is willing to provide blood, urine, and tissue samples for research
             purposes.

        Exclusion Criteria:

          -  Have received more than one prior systemic chemotherapy regimen for metastatic
             disease.

          -  Have received prior systemic taxane therapy for transitional cell carcinoma (TCC) of
             the bladder, urethra, ureter, or renal pelvis in any setting (neoadjuvant, adjuvant,
             metastatic).

          -  Have received more than one prior antiangiogenic agent (that is, bevacizumab,
             sorafenib, sunitinib) for TCC of the urothelium.

          -  Have received radiation therapy within 4 weeks (≤4 weeks) prior to randomization or
             has not recovered from toxic effects of the treatment that was given >4 weeks prior to
             randomization.

          -  Have a history of uncontrolled hereditary or acquired bleeding or thrombotic
             disorders.

          -  Have experienced a Grade ≥3 bleeding event within 3 months (≤3 months) prior to
             randomization.

          -  Have 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, or any other serious uncontrolled medical disorders.

          -  Have experienced any arterial or venothrombotic or thromboembolic events, including,
             but not limited to myocardial infarction, transient ischemic attack, or
             cerebrovascular accident, within 6 months (≤6 months) prior to randomization.

          -  Have known untreated brain metastases, uncontrolled spinal cord compression, or
             leptomeningeal disease.

          -  Have human immunodeficiency virus (HIV) infection or acquired immunodeficiency
             syndrome-related illness.

          -  Have undergone major surgery within 28 days (≤28 days) prior to randomization or
             subcutaneous venous access device placement within 7 days (≤7 days) prior to
             randomization.

          -  The participant is pregnant prior to randomization or lactating.

          -  Have a concurrent malignancy or had another malignancy within 5 years (≤5 years) of
             study enrollment.