Baltimore, Maryland 21231


RATIONALE: Vaccines made from tumor cells may help the body build an effective immune response to kill tumor cells. Giving vaccine therapy together with chemotherapy may be a more effective treatment for colorectal cancer. PURPOSE: This phase I trial is studying the side effects of vaccine therapy given together with cyclophosphamide in treating patients who have undergone surgery for liver metastases due to metastatic colorectal cancer.

Study summary:

OBJECTIVES: Primary - To evaluate the safety and feasibility of vaccination with two irradiated allogeneic colorectal carcinoma cells administered with GM-K562 cell vaccine in sequence with an immunomodulatory dose of cyclophosphamide. Secondary - To evaluate the feasibility of measuring T-cell responses to Ep-CAM as a potential surrogate target of vaccine-induced immune responses. - To assess efficacy, disease-free, and overall survival in vaccinated patients. OUTLINE: At least 1 month and no more than 3 months after the last course of adjuvant systemic chemotherapy or hepatic metastectomy, patients receive cyclophosphamide IV on day -1 and vaccine therapy comprising allogeneic colorectal carcinoma cells and K562/GM-CSF cells intradermally on day 0. Treatment repeats every month for up to 4 courses in the absence of disease progression or unacceptable toxicity. Blood is collected prior to the first vaccine administration, then one month after each (1st through 4th) immunization for correlative studies. Samples are analyzed by ELISPOT assays on peripheral blood mononuclear cells, for HLA typing and HLA-A2 expression by the standard NIH microlymphocytotoxicity test, for peptides by ELISPOT assays, and for immunologic response by other exploratory assays. After completion of study treatment, patients are followed at 28 days and then periodically thereafter.


DISEASE CHARACTERISTICS: - Histologically confirmed adenocarcinoma of the colon or rectum - Metastatic disease limited to the liver (no extrahepatic metastatic deposits) - Underwent prior complete hepatic metastasectomy and is presently without evidence of cancer (no gross disease following surgery) - No radiographic evidence of colorectal cancer at enrollment - Patients* may receive adjuvant systemic chemotherapy of colorectal cancer including, but not limited to, any of the following: - Combinations of cytotoxics such as fluoropyrimidines (fluorouracil and capecitabine), irinotecan hydrochloride, or oxaliplatin - Biologics with known activity against colorectal cancer such as bevacizumab and cetuximab NOTE: *Patients who are precluded from receiving such therapy secondary to toxicity or who refuse standard chemotherapy are also eligible - Administration of the investigational product needs to be planned for 1-3 months after the last course of chemotherapy or liver resection - At least 1 month and no more than 3 months after the last course of systemic therapy or liver resection - No colorectal cancer involving extrahepatic sites including lungs, bones, CNS, or peritoneum PATIENT CHARACTERISTICS: Inclusion criteria: - ECOG performance status 0-1 - WBC ≥ 3,500/mm^3 - ANC > 1,000/mm^3 - Platelet count > 100,000/mm^3 - Hemoglobin ≥ 9 g/dL - Serum creatinine < 2.0 mg/dL AND creatinine clearance > 60 mL/min - Serum bilirubin < 2.0 mg/dL (serum bilirubin 2.0 is acceptable in the setting of known Gilbert syndrome) - AST and ALT < 3.0 times upper limit of normal (ULN) - Alkaline phosphatase < 4 times ULN - Fertile patients must use effective contraception during and for 28 days after completion of study treatment - Negative pregnancy test - Asthma or chronic obstructive pulmonary disease that does not require daily systemic corticosteroids allowed Exclusion criteria: - Prior or currently active autoimmune disease requiring management with systemic immunosuppression, including, but not limited to, any of the following: - Inflammatory bowel disease - Systemic vasculitis - Scleroderma - Psoriasis - Multiple sclerosis - Hemolytic anemia - Immune-mediated thrombocytopenia, rheumatoid arthritis, systemic lupus erythematosus, Sjögren syndrome, sarcoidosis, or other rheumatologic disease - Active or uncontrolled medical or psychosocial problems that could be complicated by the patient's participation in the study - Evidence of active acute or chronic infection - History of other malignancies within the prior five years (excluding a history of carcinoma in situ of the cervix, superficial nonmelanoma skin cancer, and superficial bladder cancer) - Known or suspected hypersensitivity to sargramostim (GM-CSF), cyclophosphamide, pentastarch, corn, or DMSO PRIOR CONCURRENT THERAPY: - See Disease Characteristics - Recovered from all prior therapy (alopecia allowed) - More than 28 days since prior anticancer therapy, including prior systemic chemotherapy, radiotherapy, or biologic therapy - More than 28 days since prior systemic corticosteroid treatment via the oral, intramuscular, or intravenous routes - Suppositories with a steroid component are not allowed during the 28 days prior to study dosing and for the subsequent 28 days - Steroids administered via the respiratory (intranasal or inhaled) or intraarticular route that are not immunosuppressive are acceptable - Topical steroids of a strength up to 1% allowed - More than 28 days since prior surgery - Minor procedures (dental work or skin biopsy) and biliary stent placement allowed - More than 28 days since other prior anti-cancer vaccine therapy or participation in an investigational new drug trial - Concurrent hormonal therapy, including hormone replacement therapy in postmenopausal women and birth control pills, and supportive therapy with bisphosphonates allowed



Primary Contact:

Principal Investigator
Richard D. Schulick, MD, FACS
Sidney Kimmel Comprehensive Cancer Center

Backup Contact:


Location Contact:

Baltimore, Maryland 21231
United States

Clinical Research Office
Phone: 410-955-8866

Site Status: Recruiting

Data Source:

Date Processed: March 16, 2018

Modifications to this listing: Only selected fields are shown, please use the link below to view all information about this clinical trial.

Click to view Full Listing

If you would like to be contacted by the clinical trial representative please fill out the form below.