Primary Outcome Measure:
- Number of participants with adverse events [ Time Frame: up to 24 weeks ] [ Designated as safety issue: Yes ]
Our primary objective is to test whether our combined immunotherapy regimen (αDC1 vaccines + CKM) is safe and whether it can prolong time-to-progression (TTP) in patients with peritoneal surface malignancies after optimal CRS + HIPEC with standard of care chemotherapy.
- Time to disease progression [ Time Frame: 9 to 18 months ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- How long participants live after surgery [ Time Frame: 5 years ] [ Designated as safety issue: No ]
estimate overall survival (OS)
- Changes in the immune system [ Time Frame: Approximately at weeks 0, 1, 4, 20, 23, and 27 ] [ Designated as safety issue: No ]
TTP will be correlated with the development of positive DTH reaction to autologous tumor cell lysates, and may also be correlated with the changes in the blood samples and available DTH biopsies of the treated subjects.
Eligibility Criteria
- Inclusion Criteria:
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- Patients with histologically confirmed peritoneal surface malignancies, including malignant peritoneal mesothelioma and peritoneal carcinomatosis (PC) from presumed appendiceal and colorectal primary tumors. Most patients will have received extensive prior treatments, due to the recurrent nature of PC. Prior therapies involve previous CRS, local and systemic chemotherapy, and their different numbers. None of these prior treatments disqualifies the patient from receiving the protocol-mandated experimental treatment.
- Patients must be deemed able to undergo optimal cytoreductive surgery (CRS) defined as CC-score of 0 or 1 based on imaging.
Cytoreduction is defined as the burden of residual disease nodules left at the end of surgery (CC-0: no visible disease; CC-1: residual tumor nodules ≤ 2.5 mm in size; CC-2: residual tumor nodules 2.5 mm – 2.5 cm in size; CC-3: residual tumor nodules > 2.5 cm in size).
- Patients may be enrolled in the study regardless of prior chemotherapy regimens
- An ECOG performance status of 0, 1 or 2
- Age equal to 18 years or older
- Patients must be able to understand and be willing to sign a written informed consent document
- Able to swallow pills
- Must have normal organ and marrow function as defined below:
Platelet ≥ 75,000/µL Hemoglobin ≥ 9.0 g/dL Hematocrit ≥ 27.0% Absolute Neutrophil Count (ANC) ≥ 1500/µL WBC >2000/mm3 Creatinine < 1.5 x institutional upper limit of normal (ULN), OR Creatinine clearance ≥ 50 mL/min/1.73 m2 for patients with creatinine levels greater than 1.5 x ULN Total bilirubin ≤ 1.5 x ULN AST(SGOT) and ALT(SGPT) ≤ 2.5 X ULN
- Exclusion Criteria:
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- Patients on systemic immunosuppressive agents, including steroids. Patients who are able to be removed from immunosuppressives at least 3 weeks prior to the first vaccine will be considered eligible.
- Patients with active autoimmune disease or history of transplantation. Patients with indolent or chronic autoimmune disease not requiring steroid treatment are considered eligible.
- Patients who are pregnant or nursing
- Patients experiencing a cardiac events (acute coronary syndrome, myocardial infarction, or ischemia) within the 3 months prior to accrual
- Patients with a New York Heart Association classification of III or IV
- Prior allergic reaction or hypersensitivity to sulfonamides, celecoxib, or NSAIDs
