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

NCT02446093 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: PaTK02
• Study Type: interventional
• Target: 54
• Locations: 2 countries
• Sites: 3

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.

Conditions

Borderline Resectable Pancreatic Adenocarcinoma

Keywords

Borderline resectable pancreatic adenocarcinoma; Immunotherapy; Aglatimagene besadenovec; Neoadjuvant; CAN-2409

Outcome Measures

Primary Outcomes (2)

• 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.

• Survival Rate

  All eligible subjects will be followed for at least 2 additional years from the completion of primary treatment window.

  24 months

Secondary Outcomes (7)

• Overall survival (OS) from time of diagnosis

  60 months

• Overall survival (OS) from time of study enrollment

  60 months

• Progression free survival (PFS) from time of diagnosis

  60 months

• Progression free survival (PFS) from time of study enrollment

  60 months

• Resection rate

  12 weeks

Study Arms (2)

Test Arm

EXPERIMENTAL

CAN-2409 + prodrug (valacylovir or acyclovir) in combination with neoadjuvant chemoradiation or SBRT + Surgery

Biological: Aglatimagene besadenovec; Radiation: Chemoradiation; Radiation: Stereotactic body radiation therapy; Procedure: Surgery

Control Arm

ACTIVE COMPARATOR

Neoadjuvant chemoradiation or SBRT + Surgery

Radiation: Chemoradiation; Radiation: Stereotactic body radiation therapy; Procedure: Surgery

Interventions

Aglatimagene besadenovec BIOLOGICAL

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.

Also known as: CAN-2409, AdV-tk

Test Arm

Chemoradiation RADIATION

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.

Control Arm; Test Arm

Stereotactic body radiation therapy RADIATION

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.

Control Arm; Test Arm

Surgery PROCEDURE

Surgical resection should be performed within 8 weeks after completing CR or SBRT.

Control Arm; Test Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Subjects must be deemed to be in adequate health to undergo major surgery (e.g., pancreaticoduodenectomy).
• 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
• Age \> 18 years at the time of consent
• Performance status ECOG 0 or 1
• SGOT (AST) \<3x upper limit normal
• 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
• Creatinine \<2mg/dl
• Calculated creatinine clearance \> 30ml/min

You may not qualify if:

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

Sponsors & Collaborators

• Candel Therapeutics, Inc.: lead
• Mayo Clinic: collaborator

Study Sites (3)

Lee Health/Regional Cancer Center

Fort Myers, Florida, 33905, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Mexico City, 14080, Mexico

Location

MeSH Terms

Interventions

Chemoradiotherapy; Radiosurgery; Surgical Procedures, Operative

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Drug Therapy; Radiotherapy; Stereotaxic Techniques; Neurosurgical Procedures; Investigative Techniques

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2015
• First Posted: May 18, 2015
• Study Start: October 1, 2015
• Primary Completion: December 1, 2025
• Study Completion (Estimated): July 1, 2026
• Last Updated: January 8, 2024

Record last verified: 2023-05

Locations

US (2); ME (1)