PD-1 Alone or With Dendritic Cell/Renal Cell Carcinoma Fusion Cell Vaccine

Study Overview
=================
Brief Summary
-----------------
CT-011 is an investigational monoclonal antibody. Monoclonal antibodies are a type of drug that are known to target specific cells (in this case, cells in the immune system) The DC RCC Vaccine is agent that tries to help the immune system to recognize and fight against cancer cells. The purpose of this research study is to determine the safety of CT-011 alone, and in combination with the Dendritic Cell Renal Cell Carcinoma (DC RCC) vaccine. The investigators are also trying to find out what effect the combination has on the disease, and on your immune system.

Detailed Description
-----------------
This study is divided into 2 groups. The first 22 subjects will be in Group 1 and will receive CT-011 only. The next 22 subjects will be in Group 2 and will receive CT-011 and the DC RCC vaccine. Group 1: Subjects in this cohort are not required to have tumor resection (nephrectomy) to participate in this study. For subjects who are undergoing nephrectomy and for subjects undergoing resection for another metastasis, infusions of CT-011 will begin 21 to 35 days post-surgery. Subjects will receive 4 cycles of CT-011 therapy. Each cycle consists of a dose of CT-011 given on days 1, 14, and 28 intravenously. For subjects who are not undergoing nephrectomy for standard of care therapy, infusions of CT-011 will begin 21 to 28 days following registration on the study. Subjects will receive a total of four cycles of CT-011 therapy. Each cycle consists of a dose of CT-011 given on days 1, 14, and 28 intravenously. Group 2: Subjects in this cohort will have chosen to undergo a debulking nephrectomy (surgery to remove a tumor of the kidney, but not all of the cancer cells in your body) as a standard treatment for kidney cancer or have tumor lesions that are accessible (may be removed without major surgery) and are being removed to treat or diagnose their cancer. All subjects in this group will receive infusions of CT-011 21 to 35 days following tumor resection. Subjects will receive a total of 4 cycles of CT-011 therapy. Each cycle consists of a dose of CT-011 given on days 1, 14, and 28. In addition they will receive a vaccination of the DC RCC vaccine on day 8 of each cycle.

Official Title
-----------------
Phase II Study of PD-1 Blockade Alone or In Conjunction With the Dendritic Cell (DC)/Renal Cell Carcinoma (RCC) Fusion Cell Vaccination

Conditions
-----------------
Renal Cell Carcinoma

Intervention / Treatment
-----------------
* Drug: CT-011
* Biological: DC/RCC fusion vaccine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Stage IV renal cancer Measurable disease Life expectancy > 3 months Adequate organ and marrow function Exclusion Criteria: Clinical evidence of central nervous system (CNS) disease. Subjects with a history of treated brain metastasis must be stable with no evidence of disease for 3 months Clinically significant autoimmune disease HIV+ Serious intercurrent illness such as infection requiring intravenous (IV) antibiotics, or significant cardiac disease characterized by significant arrhythmia, uncontrolled hypertension, unstable ischemic coronary disease or congestive heart failure Pregnant or lactating History of clinically significant venous thromboembolism (For Cohort 2)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CT-011<br>CT-011 3 mg/kg for 4 cycles of 6 weeks | Drug: CT-011<br>* CT-011 at 3 mg/kg IV for 4 cycles of 6 weeks<br>|
| Active Comparator: CT-011 with DC/RCC fusion vaccine<br>CT-011 with DC/RCC fusion vaccine for subjects undergoing nephrectomy, resection of tumor tissue, or aspiration of malignant effusion | Drug: CT-011<br>* CT-011 at 3 mg/kg IV for 4 cycles of 6 weeks<br>Biological: DC/RCC fusion vaccine<br>* Vaccination once per cycle on Day 8 of treatment cycles 2-4<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events | Assessment of toxicity associated with treating patients with metastatic RCC with CT-011 alone or CT-011 in conjunction with DC/RCC. Toxicity was assessed and classified according to CTCAE Version 4.0. | 2 years | 
| Number of Participants With PR or CR at 2 Years | To evaluate the complete and partial response rate following completing 4 cycles of CT-011 alone or CT-011 in conjunction with DC/RCC fusion vaccine. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, (with an absolute increase of at least 5 mm), or the appearance of new lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunologic Response | To evaluate immunologic response directed against RCC and tumor specific antigens following therapy with CT-011 alone or CT-011 in conjunction with DC/RCC fusion vaccine. Immunologic response will be characterized as peak response post-therapy and ongoing response at 3 and 6 months following treatment. | 2 years | 
| Effect on Circulating Regulatory T Cells | To evaluate the effect of CT-011 alone or in conjunction with DC/RCC fusions on circulating regulatory T cells and PD-1 expression by circulating and bone marrow derived T cells. | 2 years | 
| Number of Participants Who Survived at 2 Years | To evaluate overall survival following treatment with CT-011 alone or CT-011 in conjunction with DC/RCC fusion vaccine. | 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Kidney, Metastatic, Stage IV