The purpose of this study is to characterize the safety, preliminary efficacy, and immune biologic activity of CAN-2409 + prodrug (valacyclovir or acyclovir) in subjects with borderline resectable pancreatic cancer who are being treated with neoadjuvant chemoradiation (CR) or stereotactic body radiation therapy (SBRT). The Standard of Care (SOC) Control arm will be used as a benchmark for informal comparisons of efficacy, safety, and biomarkers.
Study design is an open-label Phase 2 trial that randomizes subjects with borderline resectable pancreatic adenocarcinoma to received SOC with (Test arm) or without (Control arm) the addition of CAN-2409 + prodrug (2:1 randomization, Test: Control), beginning after completion of at least 4 months (8 cycles) of a FOLFIRINOX based induction therapy. Confirmation of borderline resectable status will be based on central radiologic review following completion of FOLFIRINOX based induction regimen. Upon enrollment, eligible subjects will receive three courses of CAN-2409 + prodrug, the first course starting prior to CR or SBRT, the second course concurrent with CR or just following completion of SBRT, and the third at time of resection. Up to 2 additional courses are allowed at the time of disease recurrence.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
54
Three courses of CAN-2409 + prodrug (valacylovir or acyclovir) will be delivered and timed with different phases of therapy: 1) after induction chemotherapy 2) during CR or post-SBRT, and 3) at time of surgery. Up to 2 additional courses of CAN-2409 + prodrug, if feasible, for subjects with disease progression or metastases.
CR will start not more than 2 months after completion of induction chemotherapy. The chemotherapy component of CR may be selected as per institutional standard of care (SOC) and protocols for administration, and may include capecitabine, 5-FU, or gemcitabine. Radiation should consist of a total dose of 45-54 Gy in 1.8-2.0 Gy fractions concurrent with chemotherapy over 3-5.5 weeks.
Lee Health/Regional Cancer Center
Fort Myers, Florida, United States
Ohio State University
Columbus, Ohio, United States
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Mexico City, Mexico
Safety grade by CTCAE version 4.0
Frequency of adverse events.
Time frame: From the time of CAN-2409 administration to 30 days after the last dose of valacyclovir.
Survival Rate
All eligible subjects will be followed for at least 2 additional years from the completion of primary treatment window.
Time frame: 24 months
Overall survival (OS) from time of diagnosis
Time from diagnosis until death from any cause.
Time frame: 60 months
Overall survival (OS) from time of study enrollment
Time from enrollment until death from any cause.
Time frame: 60 months
Progression free survival (PFS) from time of diagnosis
Time from diagnosis until first objective documentation of progression (local or distant) or death from any cause.
Time frame: 60 months
Progression free survival (PFS) from time of study enrollment
Time from study enrollment to documented disease progression or death from any cause.
Time frame: 60 months
Resection rate
Subjects will be considered to have R0 resection if all lesions are removed with negative microscopic surgical margins. Subjects will be considered to have R1 resection if all lesions are removed with any positive microscopic surgical margins.
Time frame: 12 weeks
Disease free survival (DFS) in subjects with R0 resection
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SBRT should start no more than 2 months after completion of induction chemotherapy. For SBRT, the radiation should consist of a total dose of 25-50 Gy in divided fractions over 1-2 weeks.
Surgical resection should be performed within 8 weeks after completing CR or SBRT.
Disease-free survival (DFS) will be measured from R0 resection until first objective documentation of recurrence or death from any cause.
Time frame: 60 months
Immunological biomarker characterization in tumor and peripheral blood
Immunophenotyping in the blood and in the tissue.
Time frame: 24 months