A Study of Ramucirumab in Participants With Metastatic Renal Cell Carcinoma
Condition: Metastatic Renal Cell Carcinoma
MeSH terms: Carcinoma; Carcinoma, Renal Cell
Intervention: Ramucirumab
Intervention description: Ramucirumab is an injectable solution administered as an intravenous infusion over 1 hour at a dose of 8 mg/kg day 1 of every 14-day cycle.
Intervention MeSH terms: Ramucirumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 39.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to determine whether ramucirumab is effective treatment in
      participants with metastatic renal cell carcinoma who have developed progressive disease or
      become intolerant to tyrosine kinase inhibitor therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  The participant has histologically or cytologically confirmed clear cell RCC

          -  The participant is ≥ 18 years of age

          -  The participant has an Eastern Cooperative Oncology Group performance status (ECOG PS)
             of 0-1 or Karnofsky Performance Status (KPS) ≥ 80%

          -  The participant has had a prior nephrectomy (as therapy for RCC)

          -  The participant has metastatic RCC

          -  The participant has a life expectancy of > 3 months

          -  The participant has measurable disease as defined by Response Evaluation Criteria in
             Solid Tumors (RECIST)

          -  The participant has received prior therapy with a TKI (sunitinib and/or sorafenib)
             with either disease progression on TKI therapy (progression within 60 days of the last
             dose of TKI) or intolerance to TKI (unable to continue therapy because of
             side-effects). A participant with progression during a protracted treatment break is
             not eligible unless the participant has had progression or intolerance as defined
             above

          -  The participant has resolution of all clinically significant toxic effects of prior
             cancer therapy to grade ≤ 1 by the National Cancer Institute Common Terminology
             Criteria for Adverse Events, version 3.0 (NCI-CTCAE)

          -  The participant has adequate hematological functions [absolute neutrophil count (ANC)
             ≥ 1500 cells per milliliter (cells/mL), hemoglobin ≥ 9 grams per deciliter (g/dL) and
             platelets ≥ 100,000 cells/mL]

          -  The participant has adequate hepatic function [bilirubin within normal limits (WNL),
             aspartate transaminase (AST) and/or alanine transaminase (ALT) ≤ 2.5 times the upper
             limit of normal (ULN), or ≤ 5.0 times the ULN if the transaminase elevation is due to
             liver metastases]

          -  The participant has normal renal function or mild renal dysfunction [creatinine ≤ 2.2
             milligrams per deciliter (mg/dL)]

          -  The participant's urinary protein ≤ 1+ on dipstick or routine urinalysis [(UA); if
             urine dipstick or routine analysis is ≥ 2+, a 24-hour urine for protein must
             demonstrate < 1000 (milligrams) mg of protein in 24 hours to allow participation in
             the study]

          -  The participant must have adequate coagulation function as defined by International
             Normalized Ratio (INR) ≤ 1.8 and a partial thromboplastin time (PTT) ≤ 1.5 X ULN.
             Participants on full-dose anticoagulation must be on a stable dose of oral
             anticoagulant or low molecular weight (LMW) heparin and if on warfarin must have a INR
             between 2 and 3 and have no active bleeding or pathological condition that carries a
             high risk of bleeding (for example, tumor involving major vessels or known varices)

          -  The participant is able to provide informed written consent

          -  The participant , if sexually active, is postmenopausal (last menstrual period > 2
             years prior to study), surgically sterile, or is using effective method of
             contraception in the opinion of the investigator

          -  The participant , if female, must have a negative serum pregnancy test upon entry into
             this study

          -  The participant has a normal thyroid stimulating hormone (TSH) value. Participants
             with an abnormal TSH may be eligible provided they meet all other eligibility criteria
             and have ECOG performance status 0-1. Participants with an abnormal TSH value require
             a full thyroid evaluation prior to enrollment. Endocrinology consultation may be
             performed at the discretion of the investigator

          -  The participant has serum calcium within normal limits

        Exclusion Criteria:

          -  The participant has received prior treatment with bevacizumab

          -  The participant has known brain or leptomeningeal metastases

          -  The participant has received >2 prior cytotoxic chemotherapy regimens for RCC

          -  The participant has received antitumor therapy (biologic agents, major surgery, or
             investigational agent) within 28 days prior to enrollment on study. The participant
             has received radiation therapy within 14 days prior to enrollment on study.
             Participants with metastasis in weight bearing bones at high risk for pathologic
             fracture may participate provided that appropriate surgical intervention and/or
             radiation therapy is undertaken and completed at least 28 days prior to enrollment

          -  The participant has received > 1 prior bio-immunotherapy regimens (defined as either
             interleukin-2 or interferon alpha given as monotherapy, concurrently, or sequentially
             as planned)

          -  The participant has a concurrent active malignancy other than adequately treated
             non-melanomatous skin cancer or other non-invasive carcinoma or in situ neoplasm. A
             participant with previous history of malignancy is eligible, provided that he/she has
             been disease free for > 3 years

          -  The participant has a nonhealing wound or ulcer

          -  The participant has a known alcohol or drug dependency

          -  The participant is pregnant or breastfeeding

          -  The participant has a coexisting medical or psychiatric problem of sufficient severity
             to limit compliance with the study and/or increase the risks associated with study
             participation or study drug administration or interfere with the interpretation of
             study results

          -  The participant has an ongoing or active infection, 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 participant has known human immunodeficiency virus infection or acquired
             immunodeficiency syndrome-related illness