Colon Cancer Clinical Trial
VX15/2503 and Immunotherapy in Resectable Pancreatic and Colorectal Cancer
This randomized phase I trial studies how well anti-semaphorin 4D (anti-SEMA4D) monoclonal antibody VX15/2503 with or without ipilimumab or nivolumab work in treating patients with stage I-III pancreatic cancer that can be removed by surgery or stage IV colorectal cancer that has spread to the liver and can be removed by surgery. Monoclonal antibodies, such as anti-SEMA4D monoclonal antibody VX15/2503, ipilimumab, and nivolumab, may interfere with the ability of tumor cells to grow and spread.
To evaluate the effect of the anti-SEMA4D monoclonal antibody VX15/2503 (VX15/2503) alone and VX15/2503 in combination with immune checkpoint inhibitors, ipilimumab or nivolumab, on the immune profile in the tumor microenvironment and in peripheral blood.
To extend the previously reported safety profile of single agent VX15/2503 to the combination of VX15/2503 and immune checkpoint inhibitors, ipilimumab or nivolumab, in patients with pancreatic and colorectal cancer.
Patients are randomized to 1 of 4 arms.
ARM I: Patients undergo surgery.
ARM II: Patients receive anti-SEMA4D monoclonal antibody VX15/2503 intravenously (IV) over 60 minutes on day 1. Patients then proceed to surgery 22-36 days after drug administration.
ARM III: Patients receive anti-SEMA4D monoclonal antibody VX15/2503 IV over 60 minutes and ipilimumab IV over 90 minutes on day 1. Patients then proceed to surgery 22-36 days after drug administration.
ARM IV: Patients receive anti-SEMA4D monoclonal antibody VX15/2503 IV over 60 minutes and nivolumab IV over 60 minutes on day 1. Patients then proceed to surgery 22-36 days after drug administration.
After completion of study treatment, patients are followed up at 90 days and then every 12 weeks thereafter.
For patients with pancreatic cancer:
Stage I-III cytologically or histologically-proven pancreatic adenocarcinoma
Cancer confirmed to be surgically resectable, with surgery evaluation with planned resection
Patients may have prior neoadjuvant chemotherapy, but no neoadjuvant chemoradiation
No cancer chemotherapy treatment 2 weeks prior to day 2 of treatment
For patients with metastatic colorectal cancer:
Stage IV histologically-proven colorectal adenocarcinoma
Liver metastasis confirmed to be surgically resectable, with surgery evaluation and planned resection; may have minimal extrahepatic disease that is determined to be resectable
Tumor must be confirmed to be microsatellite stable (MSS); if not already reported at a Clinical Laboratory Improvement Act (CLIA)-certified laboratory, we will be able to perform this at Emory University
No prior immunotherapy
No cancer chemotherapy treatment 2 weeks prior to day 1 of treatment
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Absolute neutrophil count â‰¥ 1,500 cells/ÂµL
Platelets â‰¥ 100,000/ÂµL
Hemoglobin â‰¥ 9.0 g/dL (may receive packed red blood cell [prbc] transfusion)
Total bilirubin â‰¤ 1.5 x the upper limit of normal (ULN)
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) â‰¤ 2.5 x ULN
Albumin â‰¥ 3.0 g/dL
Serum creatinine â‰¤ 1.5 x ULN
Calculated creatinine clearance of â‰¥ 50 mL/min
International normalized ratio (INR) â‰¤ 1.5; anticoagulation is allowed only with low molecular weight heparin (LMWH); patient receiving LMW heparin on stable therapeutic dose for more than 2 weeks or with factor Xa level < 1.1 U/mL are allowed on the trial
Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
Ability to understand and willingness to sign a written informed consent document
Female subjects of childbearing potential must agree to use adequate contraception (e.g., hormonal or barrier method of birth control; abstinence) for the duration of study treatment and 3 months after completion
Male subjects must agree to use adequate contraception (e.g., condoms; abstinence) for the duration of study treatment and 3 months after completion
Female subjects of childbearing age must have a negative serum pregnancy test at study entry
Poor venous access for study drug administration
Determined not to be a surgical candidate due to medical co-morbidities
Treatment with chronic immunosuppressants (e.g., cyclosporine following transplantation)
Prior organ allograft or allogeneic bone marrow transplantation
Subjects with any active autoimmune disease or history of known or suspected autoimmune disease except for subjects with vitiligo, resolved childhood asthma/atopy, type I diabetes mellitus, residual hypothyroidism, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration; inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
Women who are pregnant or lactating
Uncontrolled intercurrent illness including, but not limited to, human immunodeficiency virus (HIV)-positive subjects receiving combination antiretroviral therapy, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association [NYHA] class III or IV), unstable angina pectoris, ventricular arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Other medications, or severe acute/chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study
Clinical evidence of bleeding diathesis or coagulopathy
Patients with prior malignancies, including pelvic cancer, are eligible if they have been disease free for > 5 years; patients with prior in situ carcinomas are eligible provided there was complete removal
Active bacterial or fungal infections requiring systemic treatment within 7 days of treatment
Use of other investigational drugs (drugs not marked for any indication) within 28 days or at least 5 half-lives (whichever is longer) before study drug administration
History of severe hypersensitivity reactions to other monoclonal antibodies
Non-oncology vaccines within 28 days prior to or after any dose of ipilimumab
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There are 4 Locations for this study
Atlanta Georgia, 30308, United States
Atlanta Georgia, 30322, United States
Atlanta Georgia, 30342, United States
Rochester New York, 14642, United States
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