| Study Summary: |
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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.
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| Criteria: |
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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
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