A Study of LY2510924 and Sunitinib in Patients With Metastatic Renal Cell Carcinoma

Study Overview
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Brief Summary
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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.

Official Title
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Randomized, Multicenter, Open-label, Active-Controlled, Phase 2 Study of LY2510924 and Sunitinib Versus Sunitinib in Patients With Metastatic Renal Cell Carcinoma

Conditions
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Metastatic Clear Cell Renal Cell Carcinoma

Intervention / Treatment
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* Drug: LY2510924
* Drug: Sunitinib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY2510924 + Sunitinib<br>LY2510924: 20 milligram administered subcutaneously once daily, given every day of the 6 week cycle. Sunitinib: 50 milligram administered orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment. Treatment cycles will continue until disease progression, unacceptable toxicity, or another withdrawal criterion is met. | Drug: LY2510924<br>* Administered subcutaneously<br>Drug: Sunitinib<br>* Administered orally<br>|
| Active Comparator: Sunitinib<br>50 milligram administered orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment. Treatment cycles will continue until disease progression, unacceptable toxicity, or another withdrawal criterion is met. | Drug: Sunitinib<br>* Administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | PFS is defined as the time from date of study Randomization to the first date of objectively determined progressive disease(PD) or death from any cause defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.0).PD was defined as at least a 20% increase in the sum of the diameters of target lesions,taking as reference the smallest sum on study(including the baseline sum if that is the smallest).In addition to the relative increase of 20%,the sum must also demonstrate an absolute increase of at least 5 mm.The appearance of one or more new lesions was also considered PD.For participants still alive at the time of analysis and without evidence of tumor progression,PFS would be censored at the date of the most recent objective progression-free observation.For participants who receive subsequent anticancer therapy prior to objective disease progression or death,PFS was censored at the date of the last objective progression-free observation prior to the date of subsequent therapy. | Randomization to Measured Progressive Disease or Date of Death From Any Cause (Up to 67 Months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate[ORR]) | ORR is defined as the number of participants with a best response of CR and PR defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) criteria. CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Tumor marker results must have normalized. PR is defined as at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.The appearance of one or more new lesions is also considered progression. | Baseline to Date of Tumor Response or Measured Progressive Disease or Date of Death from any Cause ((Up to 67 Months) | 
| Overall Survival (OS) | OS is defined as the time from the date of study randomization to the date of death from any cause. For participants who were still alive as of the data cut-off date, OS time will be censored on the date of the participant's last contact (last contact for participants in post-discontinuation = last known alive date in mortality status). | Randomization to Date of Death from Any Cause (Up to 67 Months) | 
| Duration of Overall Response (DOR) | DOR was defined as the time from first objective status assessment of CR or PR to the first time of progression or death as a result of any cause. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) criteria. CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Tumor marker results must have normalized. PR is defined as at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD)is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. | Date of First Response to Date of Progressive Disease (Up to 67 Months) | 
| Duration of Complete Response | Duration of complete response is defined as the time from the date when the measurement criteria are met for complete response until the date of first observation of objective disease progression (taking as reference for PD the smallest measurements recorded since the treatment started). CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Tumor marker results must have normalized. Progressive Disease (PD)is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. | Date of Complete Response to the Date of Progressive Disease (Up to 67 Months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, Tumor, Metastasis