Type-1-polarized Dendritic Cell Vaccine, Interferon Alpha-2b, Rintatolimod, and Celecoxib in Treating Patients with Chemo-refractory Metastatic Colorectal Cancer
- Be able to understand and be willing to sign a written informed consent document
- Be HLA-A2 positive
- Have mCRC that has been treated with currently approved standard therapies, including fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-vascular endothelial growth factor (VEGF) therapy, and, if Kirsten rat sarcoma viral oncogene homolog (KRAS) wild type, an anti-epidermal growth factor receptor (EGFR) therapy
- Have at least 1 of the tumor sites that must be amenable to core needle biopsy and this may not be the site of disease used to measure antitumor response
- Have measurable disease based on immune-related response criteria (irRC)
- Performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1
- Platelet >= 75,000/µL
- Hemoglobin >= 9.0 g/dL
- Absolute neutrophil count (ANC) >= 1500/µL
- Creatinine < 1.5 x institutional upper limit of normal (ULN) OR creatinine clearance (CrCl) >= 50 mL/min/1.73 m^2 for subjects with creatinine levels greater than 1.5 x ULN
- Total bilirubin =< 1.5 X institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal (ULN) OR =< 5 x ULN for subjects with liver metastases
- Serum amylase and lipase within normal limits
- Is currently treated with systemic immunosuppressive agents, including steroids, are ineligible until 3 weeks after removal from immunosuppressive treatment
- Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 4 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to a previously administered agent
- Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- Has active autoimmune disease or history of transplantation
- Is a woman of child bearing potential (WOCBP) who are pregnant or nursing
- Has a history of cardiac event(s) (acute coronary syndrome, myocardial infarction, or ischemia) within 3 months of signing consent; subjects with a New York Heart Association classification of III or IV
- Has a history of upper gastrointestinal ulceration, upper gastrointestinal bleeding, or upper gastrointestinal perforation within the past 3 years; subjects with ulceration, bleeding or perforation in the lower bowel are not excluded
- Has prior allergic reaction or hypersensitivity to celecoxib, or nonsteroidal anti-inflammatory drugs (NSAIDs)
- Has an active infection requiring systemic therapy
- Has significant ascites or pleural effusion requiring drainage for symptom relief
- Has known active hepatitis B or hepatitis C infection
- Has history of asthma, or other allergic-type reactions after taking aspirin or other NSAIDs
- Has known serious hypersensitivity reactions to peg-interferon alfa-2b or interferon alfa-2b
- Has autoimmune hepatitis
- Has hepatic decompensation (Child-Pugh score > 6; = class B and C)
I. To establish whether the combination of peptide-loaded autologous alpha dendritic cell (DC)1 vaccines and tumor-selective chemokine modulation with interferon (IFN) alpha, rintatolimod, and celecoxib improves the overall survival (OS) in histocompatibility antigen (HLA)-A2+ subjects with chemo-refractory metastatic colorectal cancer (mCRC) compared to the historical control of the best supportive care.
I. To estimate the immune-related objective response rate (irORR) and the immune-related progression-free survival (irPFS) in HLA-A2+ subjects with chemo-refractory mCRC treated with the combination of peptide-loaded autologous alpha DC1 vaccines and tumor-selective chemokine modulation with celecoxib, IFN alpha and rintatolimod.
II. To estimate the changes of cluster of differentiation (CD)8+ tumor infiltrating lymphocytes (CTLs) in paired tumor tissues collected at pre- and post-treatment.
III. To estimate the changes of tumor microenvironment in paired tumor tissues collected at pre- and post-treatment.
Patients receive celecoxib orally (PO) once daily (QD), recombinant interferon alfa-2b (IFN alpha-2b) intravenously (IV) over 20 minutes, and rintatolimod IV over 120 to 150 minutes on days 1-3. Beginning course 2, patients also receive alpha-type-1-polarized dendritic cell vaccine (alpha DC1) intranodally (IN) and intradermally (ID) on day 1. Courses repeat every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for up to 3 years.
Trial Phase Phase II
Trial Type Treatment
University of Pittsburgh Cancer Institute (UPCI)
James Jinhak Lee
- Primary ID UPCI 15-023
- Secondary IDs NCI-2016-00923
- Clinicaltrials.gov ID NCT02615574