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An Open-label, Multicenter, Randomized Phase II Study Evaluating the Safety and Efficacy of Docetaxel in Combination With IMC 1121B or IMC 18F1 or Without Investigational Therapy as Second line Therapy in Patients With Metastatic Transitional Cell Carcinoma of the Bladder, Urethra, Ureter, or Renal Pelvis Following Disease Progression on First-line Platinum-based Therapy

Conditions

Bladder | Kidney | Other Urinary

Trial Phase

Phase II

Trial Purpose and Description

Trial Purpose

To evaluate the progression-free survival (PFS) in patients with metastatic transitional cell carcinoma (TCC) when treated with docetaxel monotherapy or docetaxel in combination with either the monoclonal antibody ramucirumab (IMC-1121B) drug product (hereafter referred to as ramucirumab DP) or IMC-18F1.


Participation Guidelines

Age:
18 Years and older
Gender:
Both

Eligibility Criteria

Inclusion Criteria:

  • The patient has histologically or cytologically confirmed TCC of the bladder, urethra, ureter, or renal pelvis (mixed histology allowed provided the predominant histology is TCC).
  • The patient has locally advanced or metastatic and unresectable TCC of the bladder, urethra, ureter, or renal pelvis.
  • The patient has received treatment with a platinum-containing regimen.
  • The patient had disease progression within 12 months after receiving the last dose of a platinum-containing regimen in the neoadjuvant or adjuvant setting, and/or the patient 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.
  • The patient has a life expectancy of &ge 3 months.
  • The patient has received no more than 2 prior systemic chemotherapy regimens in any setting.
  • The patient has measurable or nonmeasurable disease (based on Response Evaluation Criteria in Solid Tumors, Version 1.1 [RECIST v 1.1] guidance).
  • The patient has resolution to Grade &le 1 by National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v 4.0) of all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy except where otherwise stated in the inclusion criteria.
  • The patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
  • The patient has adequate hematologic function as defined by absolute neutrophil count (ANC) > 1500 cells/uL, hemoglobin > 9 g/dL, and platelets > 100,000 cells/uL and has not received blood or blood components transfusion for &ge 2 weeks prior to the laboratory test.
  • The patient has adequate coagulation function as defined by international normalized ratio (INR) &le 1.5 and a partial thromboplastin time (PTT) &le 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 &le3 and have no active bleeding (defined as within 14 days prior to randomization) or pathological condition that carries a high risk of bleeding (eg, tumor involving major vessels or known varices).
  • The patient has adequate renal function as defined by creatinine clearance > 40 mL/min measured either by 24-hour urine collection or calculated by the Cockcroft-Gault equation.

  • The patient&rsquos urinary protein is &le1+ on dipstick or routine urinalysis if urine protein &ge2+, a 24-hour urine collection must demonstrate < 1000 mg of protein in 24 hours to allow participation in the study.

  • The patient, if female, is surgically sterile, postmenopausal, or compliant with a highly effective contraceptive method during and for 12 weeks after the treatment period (oral hormonal contraception alone is not considered highly reliable and must be used in combination with a barrier method). If male, the patient is surgically sterile or compliant with a contraceptive regimen during and for 12 weeks after the treatment period.

  • The patient is able to provide signed informed consent and is amenable to compliance with protocol schedules and testing.

  • The patient is > 18 years of age.

Exclusion Criteria:

  • The patient has received more than one prior systemic treatment regimen for metastatic disease.
  • The patient has received prior systemic taxane therapy (except for prior paclitaxel therapy, which is allowed) for TCC of the bladder, urethra, ureter, or renal pelvis in any setting (neoadjuvant, adjuvant, metastatic). Prior intravesical taxane therapy is allowed.
  • The patient has received more than one prior antiangiogenic agent (ie, bevacizumab, sorafenib, sunitinib) for TCC of the bladder, urethra, ureter, or renal pelvis.
  • The patient has received radiation therapy (including full-dose pelvic radiotherapy) within 4 weeks prior to randomization.
  • The patient has a history of uncontrolled hereditary or acquired bleeding or thrombotic disorders.
  • The patient has experienced a Grade &ge 3 bleeding event (eg, via gastric ulcers, gastric varices, or gross hematuria) within 3 months prior to randomization.
  • The patient 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 in the opinion of the investigator.
  • The patient 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.

  • The patient has known brain metastases, uncontrolled spinal cord compression, or leptomeningeal disease.

  • The patient has an ongoing or active infection requiring parenteral antibiotic, antifungal, or antiviral therapy.

  • The patient has known human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness.

  • The patient has received a prior autologous or allogeneic organ or tissue transplantation.
  • The patient has undergone major surgery within 28 days prior to randomization, or subcutaneous venous access device placement within 7 days prior to randomization.

  • The patient has had a serious nonhealing wound, ulcer, or bone fracture within 28 days prior to randomization.

  • The patient has an elective or planned major surgery to be performed during the course of the trial.

  • The patient is pregnant (confirmed within 7 days prior to randomization by serum beta human chorionic gonadotropin [&beta-hCG] pregnancy test) or lactating.

  • The patient has a concurrent active malignancy other than adequately treated nonmelanomatous skin cancer, curatively treated cervical carcinoma in situ, other noninvasive carcinoma or in situ neoplasm, or prostate cancer with an undetectable prostatespecific antigen (PSA) and no current treatment with hormone therapy. A patient with previous history of malignancy is eligible, provided that he/she has been disease-free for > 2 years.

  • The patient has an acute/subacute bowel obstruction or history of chronic diarrhea requiring ongoing medical intervention.

  • The patient has a history gastrointestinal perforation and/or fistula within 6 months prior to randomization.

  • The patient has active diverticulitis.

  • The patient has a known hypersensitivity to docetaxel or other drugs formulated with polysorbate 80.

  • The patient has a known hypersensitivity to agents of similar biologic composition as ramucirumab DP, IMC-18F1, or other agents that specifically target VEGF.

Sponsor:
Imclone Systems, Inc.
Dates:
03/19/2013
Last Updated:
Study HIC#:
1211011153