A Study of Ramucirumab plus Docetaxel in Participants with Urothelial Cancer.
- Conditions
- ocally advanced or unresectable or metastatic urothelial carcinoma whohave had disease progression on or after one prior first-line platinumbasedchemotherapyMedDRA version: 20.0Level: LLTClassification code 10064467Term: Urothelial carcinomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-003655-66-IT
- Lead Sponsor
- ELI LILLY & COMPANY, LILLY CORPORATE CENTER
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 524
1) Histologically or cytologically confirmed, locally advanced orunresectable or metastatic urothelial (transitional cell) carcinoma of the bladder, urethra, ureter, or renal pelvis. Patients with mixed pathology are eligible only if they have predominantly transitional cell tumor based on local pathology review.
2) Demonstrated disease progression while on a platinum-containing regimen in the first-line setting or within 14 months after completing the first-line platinum regimen. Patients who received treatment with one immune checkpoint inhibitor (for example PD-1, PDL1, CTLA4) regimen may have a longer interval since prior platinum-containing therapy (=24 months), as noted in Inclusion Criterion [4].
3) A life expectancy of =3 months, in the judgment of the investigator.
4) The patient has received no more than one prior systemic chemotherapy regimen in the relapsed or metastatic setting. Prior cytotoxic therapy in an adjuvant or neoadjuvant setting is not considered as a prior line of systemic chemotherapy in the relapsed or metastatic setting. Prior treatment with intravesicular chemotherapy, bacillus Calmette-Guérin (BCG), or platinum given as a radiation sensitizing agent will not be considered as a systemic line of treatment. Prior treatment with no more than one prior immune checkpoint inhibitor is permitted and will not be considered as a line of systemic chemotherapy. Patients enrolling after immune checkpoint inhibitor therapy must have demonstrated disease progression while on that therapy or within 24 months after the last dose of that therapy.
5) Measurable disease or nonmeasurable but evaluable disease as defined by Response Evaluation Criteria in Solid Tumors, Version 1.1
6) Resolution, except where otherwise stated in the inclusion criteria, of all clinically significant toxic effects of prior chemotherapy, surgery, or radiotherapy to Grade =1 by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0.
7) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
8) The patient has adequate hematologic function and has not received blood or blood components transfusion within 2 weeks prior to thelaboratory test.
9) Adequate coagulation function as defined by international normalized ratio (INR) =1.5 and a partial thromboplastin time (PTT) =1.5 × upper limit of normal (ULN) if not receiving anticoagulation therapy. Patients on full-dose anticoagulation must be on a stable dose of oral anticoagulant or low molecular weight heparin. If on warfarin, the patient must have an INR =3 and have no active bleeding (defined as within 14 days prior to randomization, excluding trace hematuria) or pathological condition that carries a high risk of bleeding.
10) Adequate hepatic function as defined by bilirubin within normal limits (WNL), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =3.0 × ULN, and alkaline phosphatase (AP) =2.5 × ULN.
11) The patient does not have:• cirrhosis at a level of Child-Pugh B (or worse), or• cirrhosis and a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites resulting from cirrhosis and requiring ongoing treatment with diuretics and/or paracentesis.
12) Adequate renal function as defined by creatinine clearance >30
mL/min either as measured by 24-hour urine collection or as calculated. 13) The patient's urinary protein is =1+ on dipsti
The patient has received more than one prior systemic
chemotherapy regimen for metastatic disease (except as noted in
Inclusion Criterion [4]). A treatment regimen must consist of a
minimum of 2 cycles to be considered as a prior regimen.
1) The patient has received prior systemic taxane therapy for TCC of the bladder, urethra, ureter, or renal pelvis in any setting (neoadjuvant,
adjuvant, metastatic). Prior intravesical taxane therapy is allowed and will not be considered as a prior line of systemic therapy.
2) The patient has received more than one prior antiangiogenic agent
(that is, bevacizumab, sorafenib, sunitinib) for TCC of the urothelium.
3) The patient has received radiation therapy (including full-dose pelvic
radiotherapy) within 4 weeks prior to randomization or has not
recovered from toxic effects of the treatment that was given >4 weeks
prior to randomization. Single fraction radiotherapy for palliative bone
stabilization within 4 weeks prior to randomization is allowed. If any
tumor lesion is administered radiotherapy, then it cannot be considered
for response assessment.
4) The patient has a history of uncontrolled hereditary or acquired
bleeding or thrombotic disorders.
5) The patient has experienced a Grade =3 bleeding event (for ex, via gastric ulcers, gastric varices, rectal bleeding, or gross hematuria) within 3 months prior to randomization. Patients must have
complete resolution of any prior bleeding event prior to randomization.
6) The patient has uncontrolled intercurrent illness, including, but not limited to symptomatic anemia, uncontrolled hypertension (>160 mm Hg
systolic and/or >100 mm Hg diastolic, despite antihypertensive medication), symptomatic congestive heart failure, unstable angina
pectoris, symptomatic or poorly controlled cardiac arrhythmia, psychiatric illness, or any other serious uncontrolled medical disorders in
the opinion of the investigator.
7) The patient has experienced any arterial or venothrombotic or
thromboembolic events, including, but not limited to myocardial
infarction, transient ischemic attack, or cerebrovascular accident, within
6 months prior to randomization.
8) The patient has known untreated brain metastases, uncontrolled
spinal cord compression, or leptomeningeal disease. (Note: A brain
scan via computed tomography [CT] with contrast or magnetic
resonance imaging [MRI] is to be performed only after study eligibility is
confirmed, to detect the presence of intracranial metastasis.)
9) The patient has an ongoing or active infection requiring antibiotic,
antifungal, or antiviral therapy.
10) The patient has known human immunodeficiency virus (HIV)
infection or acquired immunodeficiency syndrome-related illness.
11) The patient has received a prior autologous or allogeneic organ or
tissue transplantation.
12) The patient:
• 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
(IP) or non-approved use of a drug or device, 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 antiangiogenic therapy within 28 days prior to
randomization.
13) The patient has undergone major surgery within 28 days prior to
randomization or subcutaneous venous access device placement within 7
days prior to randomization.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method