A Study of Ramucirumab in Participants With Metastatic Renal Cell Carcinoma

Study Overview
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Brief Summary
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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.

Detailed Description
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The Primary objective is to determine the best objective response rate (ORR) of ramucirumab when administered to participants with metastatic renal cell carcinoma (RCC) whose disease has progressed during therapy with a tyrosine kinase inhibitor (TKI, sunitinib and/or sorafenib) or who have developed intolerance to these agents.

Official Title
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Phase II Single Arm Study of IMC-1121B in Patients With Metastatic Renal Cell Carcinoma With Disease Progression on or Intolerance to Tyrosine Kinase Inhibitor Therapy

Conditions
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Metastatic Renal Cell Carcinoma

Intervention / Treatment
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* Biological: Ramucirumab


Participation Criteria
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Eligibility Criteria
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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

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ramucirumab<br>Intravenous infusion at 8 milligrams per kilogram (mg/kg) on day 1 of every 14-day cycle. | Biological: Ramucirumab<br>* 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.<br>* Other names: LY3009806;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Objective Response (Objective Response Rate) | The percentage of participants with a best overall response of confirmed complete response (CR) or partial response (PR) as classified according to Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. CR is the disappearance of all target and non-target lesions and normalization of tumor marker levels. PR is having at least a 30% decrease in the sum of the longest diameter of target lesions without new lesions and progression of non-target lesions. The percentage of participants with objective response=(number of participants whose best overall response during therapy is CR or PR/number of participants treated)*100. | First dose to date of objective progressive disease or death due to any cause (up to 34 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival | Progression-free survival (PFS) is measured from the date of the first dose to the first documented date of disease progression as classified according to Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria or death from any cause. Disease progression is having at least a 20% increase in the sum of the longest diameter of target lesions and/or unequivocal progression of a non-target lesion and/or detection of a new lesion. Data for participants whose disease does not progress or for whom no post-baseline assessment is made are censored at the day of their last tumor assessment. Data for participants whose disease does not progress who are subsequently lost to follow-up are also censored at the day of their last tumor assessment. | First dose to measured progressive disease or death due to any cause (up to 34 months) | 
| Percentage of Participants Showing Disease Control at Week 12 | Participants who were alive and did not experience disease progression were considered to have disease control at 12 weeks. Disease control was based on lack of disease progression using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. According to RECIST criteria, disease progression was having at least a 20% increase in the sum of the longest diameter of target lesions and/or unequivocal progression of non-target lesion and/or detection of new lesion. Participants whose disease progression was symptomatic were not considered to have disease control. The percentage of participants showing disease control=(number of participants who did not have disease or symptomatic progression at Week 12/number of participants treated)*100. | Week 12 [Cycle 6 (1 cycle=14 days)] | 
| Percentage of Participants With Objective Response (Objective Response Rate) at 12 Weeks | The percentage of participants with a confirmed best overall response of complete response (CR) or partial response (PR) at Week 12, as classified according to Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. CR is the disappearance of all target and non-target lesions and the normalization of tumor marker levels. PR is having at least a 30% decrease in the sum of the longest diameter of target lesions without new lesions and progression of non-target lesions. The percentage of participants with objective response=(number of participants whose best overall response achieved at 12 weeks was CR or PR/number of participants treated)*100. | Week 12 [Cycle 6 (1 cycle=14 days)] | 
| Median Duration of Overall Response | Duration of response is the interval from the date of initial documented response [confirmed complete response (CR) or partial response (PR)] to the first documented date of disease progression as classified according to Response Evaluation Criteria In Solid Tumors (RECIST version 1.0) criteria, or initiation of other (or additional) antitumor therapy is first reported, or death due to any cause. CR is the disappearance of all target and non-target lesions and the normalization of tumor marker levels. PR is having at least a 30% decrease in the sum of the longest diameter of target lesions without new lesions and progression of non-target lesions. Disease progression is having at least a 20% increase in the sum of the longest diameter of target lesions and/or unequivocal progression of a non-target lesion and/or detection of a new lesion. Data from participants who did not relapse were censored on the day of their last tumor assessment. | Time of first response (CR or PR) to disease progression, initiation of other (or additional) antitumor therapy, or death due to any cause (up to 34 months) | 
| Minimum Concentration (Cmin) of Ramucirumab |  | Immediately prior to the Week 32 infusion treatment [Cycle 16 (1 cycle=14 days)] | 
| Maximum Concentration (Cmax) of Ramucirumab |  | 1 hour after the end of the Week 32 infusion treatment [Cycle 16 (1 cycle=14 days)] | 
| Summary Listing of Participants Reporting Drug-Related Treatment-Emergent Adverse Events | Data presented are the number of participants who experienced treatment-emergent adverse events (TEAE), serious adverse events (SAE), Grade 3 or 4 TEAE, or adverse events (AE) leading to discontinuation of treatment that were considered to be related to ramucirumab. A summary of SAEs and other nonserious AEs, regardless of causality, is located in the Reported Adverse Events section. | First dose to study completion (up to 34 months) plus 30-day safety follow-up |