A Study of Ramucirumab (LY3009806) Plus Docetaxel in Participants With Urothelial Cancer (RANGE)

Lilly

Status and phase: Completed; Phase 3

Conditions: Urothelial Carcinoma

Treatments: Drug: Docetaxel; Drug: Ramucirumab; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02426125

I4T-MC-JVDC (Other Identifier)

2014-003655-66 (EudraCT Number)

15679

Details and patient eligibility

About

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.

Enrollment: 530 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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530 participants in 2 patient groups, including a placebo group

Ramucirumab + Docetaxel

Experimental group

Description:

Ramucirumab (10 milligram/kilogram \[mg/kg\]) intravenously (IV) plus docetaxel (75 milligram/square meter \[mg/m²\]) IV on day 1 of each 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.

Treatment:

Drug: Docetaxel

Drug: Ramucirumab

Placebo + Docetaxel

Placebo Comparator group

Description:

Placebo IV plus docetaxel (75 mg/m²) IV on day 1 of each 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.

Treatment:

Drug: Placebo

Drug: Docetaxel