RECRUITING

Intra-tumoral Mitazalimab (CD40 Antibody) With Irreversible Electroporation (IRE) in Locally Advanced Pancreas Cancer

Conditions

Pancreatic Cancer Irreversible electroporation (IRE)NanoKnife immunotherapy CD40 Locally advanced pancreatic cancer

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is a phase I study of an agonistic CD40 antibody (mitazalimab) injected intratumorally at the time of surgical IRE in patients with locally advanced pancreatic cancer. Intratumoral delivery has potential to be more effective than systemic (intravenous) delivery while decreasing the systemic side effects of immunotherapy. We hypothesize that local delivery of mitazalimab at the time of IRE in patients with locally advanced pancreatic cancer will be safe, augment the immune effects of IRE, and decrease the risk of recurrence.

Official Title

Phase 1 Clinical Trial of Intra-tumoral Mitazalimab (CD40 Antibody) With Irreversible Electroporation (IRE) in Locally Advanced Pancreas Cancer

Quick Facts

Study Start:2024-06-25

Study Completion:2029-08

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06205849

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Provision of signed and dated informed consent form * Stated willingness to comply with all study procedures and availability for the duration of the study * Histologically/cytologically-confirmed pancreatic ductal adenocarcinoma (PDAC) * Persons, aged \> 18 years of age, as PDAC is extremely rare in pediatric populations. * Locally advanced disease that is not amenable to surgical resection. Locally advanced PDAC cases will be identified per the definition developed by the Alliance for Clinical Trials in Oncology\[53\]. Per this definition, locally advanced PDAC is defined as presence of any one or more of the following on CT: * Occlusion of the superior mesenteric vein (SMV) and/or portal vein (PV) that is not amenable to resection and venous reconstruction * Interface between tumor and hepatic artery that is not amenable to resection and reconstruction * Interface between the tumor and superior mesenteric artery (SMA) measuring \> 180º of the circumference of the vessel wall * Interface between the tumor and celiac axis measuring \> 180º of the circumference of the vessel wall that is not amenable to resection * ECOG Performance Status of 0-2 * Have adequate organ function per criteria below: * Absolute neutrophil count (ANC) ≥ 1.5x109/L * Platelets ≥ 100x109/L * Hemoglobin ≥9 g/dL * Serum creatinine ≤1.5 x ULN OR creatinine clearance ≥40 mL/min (as calculated by Modified Cockcroft-Gault formula) * Serum total bilirubin ≤ 1.5 X ULN * AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN * A minimum of 4 months of FOLFIRINOX-based systemic chemotherapy * High quality imaging triphasic CT scan contrast-enhanced dynamic MRI of abdomen and either contrast-enhanced or non-contrast CT of chest and pelvis that demonstrate no evidence of metastatic disease within 30 days of enrollment * FDG-PET imaging (skullbase-midthigh) at any timepoint between diagnosis and study intervention to determine whether tumor is PET-avid and evaluate for extra-pancreatic metastatic disease, as suggested by NCCN guidelines for high-risk patients. * Tumor amenable to "in situ" (complete) ablation with maximum primary tumor dimension \< 4.0 cm * For participants able to become pregnant: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method until the study intervention and for an additional 1 month after the study intervention. * For participants able to cause a pregnancy: use of condoms or other methods to ensure effective contraception with partner for 1 month after study intervention.	* Pregnancy or lactation * Known allergic reactions to components of the mitazalimab solution (L-Histidine, trehalose, or polysorbate 20) * Fever \> 38 degrees C within 14 days of study intervention * Treatment with another investigational drug or other intervention within 30 days of enrollment * Prior treatment with a CD40 antibody * History of severe auto-immune disease * The presence of metal fiducials or embolization coils within the tumor. * Prior receipt of radiation therapy to the pancreas * The presence of implanted metallic cardiac stimulation devices within the chest * Uncontrolled cardiac arrhythmias that prevent synchronization of pulse delivery with the refractory period of the cardiac cycle * Immunosuppressive doses of systemic medications, such as corticosteroids or absorbed topical corticosteroids (doses \> 10 mg/day prednisone or equivalent) must be discontinued at least 2 weeks (14 days) before study treatment administration. Physiologic doses of corticosteroids (≤ 10 mg/day of prednisone or its equivalent) or short pulses of corticosteroids (≤ 3 days) may be permitted. * Any medical condition that precludes major abdominal surgery under general anesthesia * Presence of distant metastatic disease (including positive peritoneal cytology) on staging laparoscopy and/or exploratory laparotomy at any timepoint.

Inclusion Criteria

Exclusion Criteria

* Provision of signed and dated informed consent form
* Stated willingness to comply with all study procedures and availability for the duration of the study
* Histologically/cytologically-confirmed pancreatic ductal adenocarcinoma (PDAC)
* Persons, aged \> 18 years of age, as PDAC is extremely rare in pediatric populations.
* Locally advanced disease that is not amenable to surgical resection. Locally advanced PDAC cases will be identified per the definition developed by the Alliance for Clinical Trials in Oncology\[53\]. Per this definition, locally advanced PDAC is defined as presence of any one or more of the following on CT:
* Occlusion of the superior mesenteric vein (SMV) and/or portal vein (PV) that is not amenable to resection and venous reconstruction
* Interface between tumor and hepatic artery that is not amenable to resection and reconstruction
* Interface between the tumor and superior mesenteric artery (SMA) measuring \> 180º of the circumference of the vessel wall
* Interface between the tumor and celiac axis measuring \> 180º of the circumference of the vessel wall that is not amenable to resection
* ECOG Performance Status of 0-2
* Have adequate organ function per criteria below:
* Absolute neutrophil count (ANC) ≥ 1.5x109/L
* Platelets ≥ 100x109/L
* Hemoglobin ≥9 g/dL
* Serum creatinine ≤1.5 x ULN OR creatinine clearance ≥40 mL/min (as calculated by Modified Cockcroft-Gault formula)
* Serum total bilirubin ≤ 1.5 X ULN
* AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN
* A minimum of 4 months of FOLFIRINOX-based systemic chemotherapy
* High quality imaging triphasic CT scan contrast-enhanced dynamic MRI of abdomen and either contrast-enhanced or non-contrast CT of chest and pelvis that demonstrate no evidence of metastatic disease within 30 days of enrollment
* FDG-PET imaging (skullbase-midthigh) at any timepoint between diagnosis and study intervention to determine whether tumor is PET-avid and evaluate for extra-pancreatic metastatic disease, as suggested by NCCN guidelines for high-risk patients.
* Tumor amenable to "in situ" (complete) ablation with maximum primary tumor dimension \< 4.0 cm
* For participants able to become pregnant: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method until the study intervention and for an additional 1 month after the study intervention.
* For participants able to cause a pregnancy: use of condoms or other methods to ensure effective contraception with partner for 1 month after study intervention.

* Pregnancy or lactation
* Known allergic reactions to components of the mitazalimab solution (L-Histidine, trehalose, or polysorbate 20)
* Fever \> 38 degrees C within 14 days of study intervention
* Treatment with another investigational drug or other intervention within 30 days of enrollment
* Prior treatment with a CD40 antibody
* History of severe auto-immune disease
* The presence of metal fiducials or embolization coils within the tumor.
* Prior receipt of radiation therapy to the pancreas
* The presence of implanted metallic cardiac stimulation devices within the chest
* Uncontrolled cardiac arrhythmias that prevent synchronization of pulse delivery with the refractory period of the cardiac cycle
* Immunosuppressive doses of systemic medications, such as corticosteroids or absorbed topical corticosteroids (doses \> 10 mg/day prednisone or equivalent) must be discontinued at least 2 weeks (14 days) before study treatment administration. Physiologic doses of corticosteroids (≤ 10 mg/day of prednisone or its equivalent) or short pulses of corticosteroids (≤ 3 days) may be permitted.
* Any medical condition that precludes major abdominal surgery under general anesthesia
* Presence of distant metastatic disease (including positive peritoneal cytology) on staging laparoscopy and/or exploratory laparotomy at any timepoint.

Contacts and Locations

Study Contact

Shakeela Dad

CONTACT

858-822-5376

sdad@health.ucsd.edu

Principal Investigator

Rebekah R White, MD

PRINCIPAL_INVESTIGATOR

University of California, San Diego

Study Locations (Sites)

UCSD Moores Cancer Center

La Jolla, California, 92093

United States

Collaborators and Investigators

Sponsor: University of California, San Diego

Rebekah R White, MD, PRINCIPAL_INVESTIGATOR, University of California, San Diego

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-06-25

Study Completion Date2029-08

Study Record Updates

Study Start Date2024-06-25

Study Completion Date2029-08

Terms related to this study

Keywords Provided by Researchers

Irreversible electroporation (IRE)
NanoKnife
immunotherapy
CD40
Locally advanced pancreatic cancer

Additional Relevant MeSH Terms

Pancreatic Cancer