Neoadjuvant CAN-2409 in Combination With Chemoradiation or SBRT for Borderline Resectable Pancreatic Adenocarcinoma

Borderline Resectable Pancreatic Adenocarcinoma Clinical Trial

— PaTK02  

Official title:

Neoadjuvant CAN-2409 Plus Prodrug in Combination With Chemoradiation or Stereotactic Body Radiation Therapy for Borderline Resectable Pancreatic Adenocarcinoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02446093
• Other study ID #: PaTK02
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 2015
• Est. completion date: July 2026

Study information

• Verified date: May 2023
• Source: Candel Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 54
• Est. completion date: July 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Borderline Resectable Pancreatic Adenocarcinoma

Intervention

Biological:
• Aglatimagene besadenovec
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.

Radiation:
• Chemoradiation
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.
• Stereotactic body radiation therapy
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.

Procedure:
• Surgery
Surgical resection should be performed within 8 weeks after completing CR or SBRT.

Locations

Country	Name	City	State
Mexico	Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran	Mexico City
United States	Ohio State University	Columbus	Ohio
United States	Lee Health/Regional Cancer Center	Fort Myers	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Candel Therapeutics, Inc.	Mayo Clinic

Countries where clinical trial is conducted

United States,  Mexico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety grade by CTCAE version 4.0	Frequency of adverse events.	From the time of CAN-2409 administration to 30 days after the last dose of valacyclovir.
Primary	Survival Rate	All eligible subjects will be followed for at least 2 additional years from the completion of primary treatment window.	24 months
Secondary	Overall survival (OS) from time of diagnosis	Time from diagnosis until death from any cause.	60 months
Secondary	Overall survival (OS) from time of study enrollment	Time from enrollment until death from any cause.	60 months
Secondary	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.	60 months
Secondary	Progression free survival (PFS) from time of study enrollment	Time from study enrollment to documented disease progression or death from any cause.	60 months
Secondary	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.	12 weeks
Secondary	Disease free survival (DFS) in subjects with R0 resection	Disease-free survival (DFS) will be measured from R0 resection until first objective documentation of recurrence or death from any cause.	60 months
Secondary	Immunological biomarker characterization in tumor and peripheral blood	Immunophenotyping in the blood and in the tissue.	24 months