Clinical trial NCT02446093: Neoadjuvant CAN-2409 in Combination With Chemoradiation or SBRT for Borderline Resectable Pancreatic Adenocarcinoma
Official title: Neoadjuvant CAN-2409 Plus Prodrug in Combination With Chemoradiation or Stereotactic Body Radiation Therapy for Borderline Resectable Pancreatic Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Borderline Resectable Pancreatic Adenocarcinoma
Keywords: Borderline resectable pancreatic adenocarcinoma
Immunotherapy
Aglatimagene besadenovec
Neoadjuvant
CAN-2409
Lead sponsor: Candel Therapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Mayo Clinic
First posted: 2015-05-18
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Pathological diagnosis of pancreatic adenocarcinoma adequately treated with a FOLFIRINOX based induction chemotherapy for at least 4 months such that they are a candidate for localized therapy with CR or SBRT followed by surgery with or without major vascular resection.
2. Subjects must be deemed to be in adequate health to undergo major surgery (e.g., pancreaticoduodenectomy).
3. Tumor accessible for injection by EUS or CT-guidance, considered potentially resectable at time of diagnosis, and classified as borderline resectable based on central radiologic review of CT scans performed following completion of FOLFIRINOX based induction chemotherapy. Resection may include major vascular resection with reconstruction as needed.

   Criteria for borderline resectable disease status:
   * No distant metastasis or lymph node involvement outside the planned resection field.
   * Venous involvement of the superior mesenteric vein (SMV) or portal view (PV) with distortion or narrowing of the vein or occlusion of the vein with suitable vessel proximal and distal, allowing for safe resection and replacement
   * Gastroduodenal artery encasement up to the hepatic artery with either short segment encasement or direct tumor abutment of the hepatic artery, without extension to the celiac axis
   * Tumor abutment of the superior mesenteric artery (SMA) not to exceed \> 180 degrees of the circumference of the vessel wall
4. Age \> 18 years at the time of consent
5. Performance status ECOG 0 or 1
6. SGOT (AST) \<3x upper limit normal
7. Total bilirubin \<2mg/dl

   * Subjects with biliary obstruction can be enrolled if AST and bilirubin do not meet criteria but must meet the criteria after stenting before starting treatment
8. Creatinine \<2mg/dl
9. Calculated creatinine clearance \> 30ml/min
10. WBC \> 3000/mm\^3
11. Absolute neutrophil count (ANC) \> 1000/mm\^3
12. Platelets \> 100,000/mm\^3
13. Hemoglobin \> 9g/dl
14. Signed, written informed consent

Exclusion Criteria:

1. Primary hepatic dysfunction including known cirrhosis or active hepatitis. Subjects with biliary obstruction must be stented prior to initiating treatment
2. Evidence of clinically significant pancreatitis as determined by the investigator
3. Evidence of significant ascites as determined by investigator
4. Subjects on systemic corticosteroid (\>10 mg prednisone per day or equivalent), systemic immunomodulators, or other systemic immunosuppressive drugs
5. Known to be HIV+
6. Pregnant or breast-feeding. Female subjects of childbearing age must have negative serum or urine pregnancy test within 2 weeks of beginning protocol therapy
7. Other current malignancy (except squamous or basal cell skill cancers)
8. Other serious co-morbid illnesses or compromised organ function
9. Known sensitivity or allergic reactions to acyclovir or valacyclovir

Primary outcomes:
measure: Safety grade by CTCAE version 4.0
timeFrame: From the time of CAN-2409 administration to 30 days after the last dose of valacyclovir.
measure: Survival Rate
timeFrame: 24 months
Secondary outcomes:
measure: Overall survival (OS) from time of diagnosis
timeFrame: 60 months
measure: Overall survival (OS) from time of study enrollment
timeFrame: 60 months
measure: Progression free survival (PFS) from time of diagnosis
timeFrame: 60 months
measure: Progression free survival (PFS) from time of study enrollment
timeFrame: 60 months
measure: Resection rate
timeFrame: 12 weeks
measure: Disease free survival (DFS) in subjects with R0 resection
timeFrame: 60 months
measure: Immunological biomarker characterization in tumor and peripheral blood
timeFrame: 24 months
Other outcomes:
Locations:
city: Fort Myers
country: United States
facility: Lee Health/Regional Cancer Center
state: Florida
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Mexico City
country: Mexico
facility: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Study officials:
References: