A Study of LY2510924 and Sunitinib in Patients With Metastatic Renal Cell Carcinoma
Condition: Metastatic Clear Cell Renal Cell Carcinoma
MeSH terms: Carcinoma; Carcinoma, Renal Cell
Intervention: LY2510924; Sunitinib
Intervention description: Administered subcutaneously; Administered orally
Intervention MeSH terms: Sunitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 110.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Cancer; Tumor; Metastasis

Summary:

      To compare the progression free survival of LY2510924 plus sunitinib therapy versus sunitinib
      in the first-line setting for patients with metastatic clear-cell renal cell carcinoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Evidence of histologically confirmed renal cell carcinoma (RCC) with metastases with a
             component of clear (conventional) cell histology

          -  A diagnosis of metastatic renal cell carcinoma (RCC) and have not received prior
             treatment with systemic (adjuvant or neoadjuvant) therapy for renal cell carcinoma
             (RCC) (including targeted therapy such as tyrosine kinase inhibitors or bevacizumab,
             immunotherapy, chemotherapy, hormonal, or investigational therapy)

          -  Evidence of measurable disease as defined by Response Evaluation Criteria in Solid
             Tumors (RECIST) version 1.1. Computed tomography (CT) or magnetic resonance imaging
             (MRI) should be performed within 4 weeks prior to study entry

          -  Participants who have or have not had their primary tumor removed by nephrectomy are
             allowed. Participants who have not had a nephrectomy should not be considered to need
             a nephrectomy as part of their overall therapy at the time of enrollment

          -  Performance status score of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
             scale

          -  Adequate bone marrow, liver, and renal function, as assessed by the following
             laboratory requirements, to be conducted within seven days prior to treatment: (upper
             limit of normal/lower limit of normal [ULN/LLN])

               -  hemoglobin (greater than) >8.0 g/dL (grams per deciliter)

               -  absolute neutrophil count (ANC) (greater than or equal to) ≥1.5 × 10^9/L (liter)

               -  platelet count (greater than or equal to) ≥100 × 10^9/L (liter)

               -  total bilirubin (less than or equal to) ≤ 1.5 × ULN (upper limit of normal)

               -  serum creatinine (less than or equal to) ≤2 × ULN (upper limit of normal)

               -  alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (less than or
                  equal to) ≤2.5 × ULN (upper limits of normal) [or (less than or equal to) ≤5 ×
                  ULN (upper limits of normal) for patients with liver involvement of their cancer]

               -  Prothrombin Time (PT) or International Normalized Ratio (INR) and activated
                  Partial Thromboplastin Time (aPTT) (less than or equal to) ≤1.5 x ULN (upper
                  limit of normal)

          -  For women: Must be surgically sterile (surgical procedure: bilateral tubal ligation,
             hysterectomy, bilateral oophorectomy), post-menopausal (at least 12 consecutive months
             of amenorrhea), or have a negative pregnancy test. Women of childbearing potential
             should be compliant with a medically approved contraceptive regimen (intrauterine
             device [IUD], birth control pills, or barrier device) during and for 3 months after
             the treatment period; must have a negative serum pregnancy test within 7 days before
             study enrollment, and must not be breastfeeding

          -  For men: Must be surgically sterile or compliant with a contraceptive regimen during
             and for 3 months after the treatment period

          -  Estimated life expectancy of at least 12 weeks

          -  Provide written informed consent/assent prior to any study-specific procedures

          -  No prior malignancies with the exception of stage 1 cancers definitively treated,
             carcinoma in situ (any primary site), treated non-melanoma skin cancer, superficial
             bladder tumors (Ta, Tis, and T1) or any cancer curatively treated 5 or more years
             prior to study entry

          -  Capable and willing to learn to self-administer LY2510924, or have a caregiver who is
             willing to learn and able to administer LY2510924 by subcutaneous (SC) injection and
             are able to swallow tablets

          -  Left ventricular ejection fraction (LVEF) greater than or equal to LLN as defined by
             the institution performing the scan, as assessed by Multiple Gated Acquisition (MUGA)
             scan, or from echocardiogram to be performed within 28 days prior to start of
             treatment

        Exclusion Criteria:

          -  Received prior treatment with sunitinib or LY2510924

          -  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

          -  History of active cardiovascular disease within the previous 12 months, including any
             of the following:

               -  Myocardial infarction

               -  Unstable angina

               -  Coronary artery/peripheral artery bypass graft

               -  Congestive heart failure

               -  Malignant hypertension

               -  Cerebrovascular accident or transient ischemic attack

               -  Symptomatic cardiac arrhythmias (Patients with chronic, stable, rate- controlled
                  atrial fibrillation are eligible)

          -  Exhibit uncontrolled hypertension ( [greater than] >150/100 [millimeters of mercury]
             mm/Hg despite optimal medical therapy), or history of poor compliance with
             antihypertensive treatment

          -  Evidence of bleeding diathesis, National Cancer Institute (NCI) Common Terminology
             Criteria for Adverse Events (CTCAE) Grade 3 hemorrhage (less than) <4 weeks of
             starting the study treatment, coagulopathy, or thromboembolic event

          -  Significant surgery (less than) <4 weeks of starting study treatment or a minor
             surgical procedure (less than) < 7 days prior to study treatment (Placement of a
             portacath or other venous access device does not require a waiting period)

          -  Suffer from medical, psychological, or social conditions that may interfere with the
             patient's participation in the study or evaluation of the study results

          -  Known or suspected allergy to any agent given in association with this trial

          -  Prior palliative radiotherapy to metastatic lesion(s) is/are permitted, provided there
             is at least 1 measurable lesion that has not been irradiated. Radiotherapy must have
             been completed (greater than) >2 weeks prior to starting study treatment, and
             radiation-related side effects must have resolved

          -  Pregnant or lactating women

          -  Impairment of the gastrointestinal (GI) function or GI disease that may significantly
             alter the absorption of sunitinib

          -  Current or recent (within 10 days of first dose of study treatment) daily use of
             aspirin ( [greater than] >325 [milligram] mg/day )

          -  Serious nonhealing wounds, acute or nonhealing ulcers, or bone fractures