SGI-110 in Combination With an Allogeneic Colon Cancer Cell Vaccine (GVAX) and Cyclophosphamide (CY) in Metastatic Colorectal Cancer (mCRC)

Study Overview
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Brief Summary
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This study will be looking at whether CY/GVAX in combination with SGI-110 is effective (recruits CD45RO+ T cells to the tumor which may be a marker of anti-tumor activity) and safe in patients with metastatic colon or rectum cancers.

Official Title
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A Pilot Study of SGI-110 in Combination With an Allogeneic Colon Cancer Cell Vaccine (GVAX) and Cyclophosphamide (CY) in Metastatic Colorectal Cancer (mCRC) as Maintenance Therapy

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: CY
* Biological: GVAX
* Drug: SGI-110


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented cancer of the colon or rectum who have received and are stable on first or second-line therapy regimens for metastatic colorectal cancer Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1 Adequate organ function as defined by study-specified laboratory tests Must use acceptable form of birth control through the study and for 28 days after final dose of study drug Signed informed consent form Willing and able to comply with study procedures Exclusion Criteria: Currently have or have history of certain study-specified heart, liver, kidney, lung, neurological, immune or other medical conditions Systemically active steroid use Another investigational product within 28 days prior to receiving study drug Major surgery or significant traumatic injury (or unhealed surgical wounds) occurring within 28 days prior to receiving study drug Chemotherapy, radiation, hormonal, or biological cancer therapy within 28 days prior to receiving study drug Pregnant or lactating Unwilling or unable to comply with study procedures

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: Cohort 1:CY/GVAX concurrently with SGI-110<br>During each of the four cycles, Cyclophosphamide (CY) is administered on Day 1 at 200 mg/m2, the colon cancer tumor vaccine (GVAX) is administered on Day 2 at 5E8 colon cancer cells + 5E7 Granulocyte macrophage-colony stimulating factor (GM-CSF) secreting cells, and SGI-110 is administered on Days 1-5 at 60 mg/m2. Each cycle is 28 days. Enrollment will begin first in Cohort 1 and 2. If a response to the treatment is seen in Cohorts 1 and 2, enrollment in Cohort 3 and 4 will begin. | Drug: CY<br>* CY is administered intravenously at 200 mg/m2<br>* Other names: Cyclophosphamide, Cytoxan;Biological: GVAX<br>* GVAX is administered intradermally at 5E8 colon cancer cells + 5E7 GM-CSF secreting cells<br>* Other names: Colon cancer tumor vaccine;Drug: SGI-110<br>* SGI-110 is administered subcutaneously at 60 mg/m2<br>|
| Experimental: Cohort 2: CY/GVAX after SGI-110<br>During each of the four cycles, SGI-110 is administered on Days 1-5 at 60 mg/m2, Cyclophosphamide (CY) is administered on Day 8 at 200 mg/m2, and the colon cancer tumor vaccine (GVAX) is administered on Day 9 at 5E8 colon cancer cells + 5E7 GM-CSF secreting cells. Each cycle is 28 days. Enrollment will begin first in Cohort 1 and 2. If a response to the treatment is seen in Cohorts 1 and 2, enrollment in Cohort 3 and 4 will begin. | Drug: CY<br>* CY is administered intravenously at 200 mg/m2<br>* Other names: Cyclophosphamide, Cytoxan;Biological: GVAX<br>* GVAX is administered intradermally at 5E8 colon cancer cells + 5E7 GM-CSF secreting cells<br>* Other names: Colon cancer tumor vaccine;Drug: SGI-110<br>* SGI-110 is administered subcutaneously at 60 mg/m2<br>|
| Experimental: Cohort 3: CY/GVAX<br>During each of the four cycles, Cyclophosphamide (CY) is administered on Day 1 at 200 mg/m2 and the colon cancer tumor vaccine (GVAX) is administered on Day 2 at 5E8 colon cancer cells + 5E7 GM-CSF secreting cells. Each cycle is 28 days. Enrollment will begin first in Cohort 1 and 2. If a response to the treatment is seen in Cohorts 1 and 2, enrollment in Cohort 3 and 4 will begin. | Drug: CY<br>* CY is administered intravenously at 200 mg/m2<br>* Other names: Cyclophosphamide, Cytoxan;Biological: GVAX<br>* GVAX is administered intradermally at 5E8 colon cancer cells + 5E7 GM-CSF secreting cells<br>* Other names: Colon cancer tumor vaccine;|
| Experimental: Cohort 4: SGI-110<br>During each of the four cycles, SGI-110 is administered on Days 1-5 at 60 mg/m2. Each cycle is 28 days. Enrollment will begin first in Cohort 1 and 2. If a response to the treatment is seen in Cohorts 1 and 2, enrollment in Cohort 3 and 4 will begin. | Drug: SGI-110<br>* SGI-110 is administered subcutaneously at 60 mg/m2<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in CD45RO+ tumor infiltrating lymphocytes (TILs) measured by immunohistochemistry in pre and post-treatment tumor biopsies from patients with metastatic colorectal cancer |  | 4 years | 
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability |  | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) |  | 4 years | 
| Time To Progression (TTP) |  | 4 years | 
| Progression Free Survival (PFS) |  | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Colorectal Neoplasms, Intestinal Neoplasms, Gastrointestinal Neoplasms, Digestive System Neoplasms, Neoplasms by Site, Neoplasms, Digestive System Diseases, Gastrointestinal Diseases, Colonic Diseases, Intestinal Diseases, Rectal Diseases