A Phase 1b Trial in Patients With Renal Cell Cancer
Condition: Metastatic Renal Cell Cancer
MeSH terms: Carcinoma, Renal Cell
Intervention: Drug: LY573636-sodium; Sunitinib
Intervention description: Participant specific dose based on height, weight and gender to target a specific exposure range, administered intravenously on Day 4 of a 42-day (6-week) cycle.
Dose will be escalated to reach the maximum tolerated dose (MTD). A cohort of participants enrolled after MTD will receive albumin-tailored doses.
Participants may continue on treatment until clinical or objective disease progression.; 37.5 or 50 milligrams (mg), administered orally, daily for a 42-day (6-week) cycle.
Participants may continue on treatment until clinical or objective disease progression.
Intervention MeSH terms: Sunitinib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to determine a safe dose of LY573636-sodium to be given in
      combination with sunitinib to patients with metastatic Renal Cell Carcinoma (RCC) and to
      determine any side effects that may be associated with LY573636-sodium and sunitinib
      combination in this patient population. The tumor response rate will also be assessed.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participants must have a histologically confirmed diagnosis of metastatic Renal Cell
             Carcinoma (RCC)

          -  Participants must have received no prior treatment with a cytotoxic-based chemotherapy
             regimen

          -  Participants must have measurable disease as defined by the Response Evaluation
             Criteria in Solid Tumors (RECIST) guidelines

          -  Have adequate hematologic, hepatic and renal function

          -  Have a serum albumin level greater than equal to 3.0 grams/Liter (g/L)

          -  Participants with reproductive potential should use medically approved contraceptive
             precautions during the trial and for 6 months following the last dose of study drug

          -  Exhibit participant compliance and geographic proximity that allow for adequate
             follow-up

          -  Have given written informed consent approved by Lilly and the ethical review board
             (ERB)/institutional review board (IRB) governing the site

          -  Have discontinued all previous therapies for cancer, including chemotherapy,
             radiotherapy, cancer-related hormonal therapy, or other investigational therapy, for
             at least 4 weeks (6 weeks for mitomycin-C or nitrosoureas) prior to study enrollment
             and recovered from the acute effects of therapy (except alopecia). Participants who
             have received whole-brain radiation must wait 90 days before starting study therapy

        Exclusion Criteria:

          -  Have received treatment within the last 30 days with a drug that has not received
             regulatory approval for any indication at the time of study entry

          -  Have received a prior cytotoxic chemotherapy-based systemic therapy for metastatic RCC

          -  Have had any of the following within 12 months prior to study drug administration:
             myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass
             graft, congestive heart failure (CHF), cerebrovascular accident, transient ischemic
             attack, or pulmonary embolism

          -  Ongoing cardiac arrhythmias greater than New York Health Association Class II
             (Protocol Attachment JZAI.4), atrial fibrillation of any grade, or prolongation of the
             QTc interval to greater than 450 milliseconds (msec) for males or greater than 470
             msec for females

          -  Have uncontrolled hypertension [greater than 150/100 millimeters of mercury (mm Hg)
             despite optimal medical therapy], or history of poor compliance with antihypertensive
             treatment

          -  Participants with documented central nervous system or leptomeningeal metastasis
             (brain metastasis) at the time of study entry. Participants with signs or symptoms of
             neurological compromise should have appropriate radiographic imaging performed before
             study entry

          -  Participants with serious concomitant OR pre-existing disorders, including active
             bacterial, fungal, or viral infection, incompatible with the study (at the discretion
             of the investigator)

          -  Participants receiving warfarin therapy for treatment of venous thrombosis or other
             prothrombotic conditions

          -  Participants with a second primary malignancy that could affect interpretation of the
             results. NOTE: Participants with adequately treated carcinoma of the skin (excluding
             melanoma) and participants with a prior history of malignancy who have been
             disease-free for greater than 2 years are eligible

          -  Participants who have previously completed or withdrawn from this study or any other
             study investigating LY573636

          -  Participants who have previously received sunitinib

          -  Participants who are unable to swallow capsules

          -  Participants who require concomitant use of potent Cytochrome P450 3A4 (CYP3A4)
             inducers or inhibitors

          -  Women who are pregnant or lactating