Photoradiation With Verteporfin To Facilitate Immunologic Activity Of Pembrolizumab In Unresectable, Locally Advanced Or Metastatic Pancreatic Cancer

Study Overview

Photoradiation With Verteporfin to Facilitate Immunologic Activity of Pembrolizumab in Unresectable, Locally Advanced or Metastatic Pancreatic Cancer

This phase II trial tests how well photoradiation with verteporfin and pembrolizumab plus standard of care chemotherapy works in treating patients with pancreatic cancer that cannot be removed by surgery (unresectable), that has spread to nearby tissue or lymph nodes (locally advanced) or to other places in the body (metastatic). Photoradiation uses light activated drugs, such as verteporfin, that become active when exposed to light. These activated drugs may kill tumor cells. Vertoporfin may also increase tumor response to immunotherapy. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as modified fluorouracil, leucovorin, irinotecan, and oxaliplatin (mFOLFIRINOX), work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Photoradiation with verteporfin and pembrolizumab plus standard of care chemotherapy may kill more tumor cells in patients with unresectable, locally advanced or metastatic pancreatic cancer.

PRIMARY OBJECTIVE: I. To evaluate overall response rate (ORR) per immune-mediated Response Evaluation Criteria in Solid Tumors (iRECIST) criteria in pancreatic cancer patients treated with the combination photodynamic priming (PDP) and pembrolizumab. SECONDARY OBJECTIVES: I. To evaluate ORR by 1st vs. 2nd line therapy. II. To evaluate duration of response (DOR) per iRECIST criteria in patients treated with the combination of PDP and pembrolizumab. III. To evaluate progression-free survival (PFS) per iRECIST criteria in patients treated with the combination of PDP and pembrolizumab. IV. To evaluate overall survival (OS) in patients treated with the combination of PDP and pembrolizumab. V. To evaluate toxicity profile per Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 as assessed by treating clinicians of the combination of PDP and pembrolizumab. OTHER OBJECTIVES: I. To evaluate the local and systemic immune response by evaluation of tumor directed cytotoxic lymphocytes within the primary and metastatic tumor sites using endoscopic ultrasound (EUS) guided fine needle aspiration before and after PDP. II. To evaluate the biomarkers generated by the lymphocyte cytotoxicity assays using harvested lymphocytes from these sites. III. To evaluate systemically circulating tumor directed cytotoxic lymphocyte sub-populations before and after PDP. IV. To evaluate quality of life using Quality of Life Questionnaire-Pancreatic Cancer 26 (QLQ PAN26), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). OUTLINE: Patients receive verteporfin intravenously (IV) and undergo a biopsy and intratumoral photoradiation over 60-90 minutes using EUS or computed tomography (CT) guidance on day 0. Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 6 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients also receive standard of care oxaliplatin IV over 2-6 hours, leucovorin IV over 15 minutes - 2 hours, irinotecan IV over 90 minutes, and fluorouracil IV on days 3, 15 and 29 of cycle 1 only, then on days 1, 15, and 29 of remaining cycles. Cycles repeat every 42 days for up to 6 months in the absence of disease progression or unacceptable toxicity. Patients may optionally undergo lymph node biopsy on day 2 or 3 of cycle 1. Additionally, patients undergo blood sample collection, CT, positron emission tomography (PET)/CT and optional PET/magnetic resonance imaging (MRI) on study. After completion of study treatment, patients are followed up at 30 and 90 days and every 3 months to progression then every 6 months for up to 3 years after registration.

Locally Advanced Pancreatic Adenocarcinoma
Metastatic Pancreatic Adenocarcinoma
Stage II Pancreatic Cancer AJCC v8
Stage III Pancreatic Cancer AJCC v8
Stage IV Pancreatic Cancer AJCC v8
Unresectable Pancreatic Adenocarcinoma

PROCEDURE: Biopsy
PROCEDURE: Biospecimen Collection
PROCEDURE: Computed Tomography
PROCEDURE: Endoscopic Ultrasound
DRUG: Fluorouracil
DRUG: Irinotecan
DRUG: Leucovorin
PROCEDURE: Lymph Node Biopsy
PROCEDURE: Magnetic Resonance Imaging
DRUG: Oxaliplatin
BIOLOGICAL: Pembrolizumab
DRUG: Photodynamic Therapy
PROCEDURE: Positron Emission Tomography
OTHER: Questionnaire Administration
DRUG: Verteporfin

MC230404
NCI-2024-03078 (REGISTRY Identifier) (REGISTRY: CTRP (Clinical Trial Reporting Program))
23-009036 (OTHER Identifier) (OTHER: Mayo Clinic Institutional Review Board)
MC230404 (OTHER Identifier) (OTHER: Mayo Clinic)
P01CA084203 (U.S. NIH Grant/Contract)

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	Results Reporting Dates	Study Record Updates
First Submitted 2024-04-19	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-08-27
First Submitted that Met QC Criteria 2024-04-19	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2025-09-03
First Posted (ESTIMATED) 2024-04-24	Results First Posted N/A	Last Verified 2025-08

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Treatment (verteportin, photoradiation, pembrolizumab) Patients receive verteporfin IV and undergo a biopsy and intratumoral photoradiation over 60-90 minutes using EUS or CT guidance on day 0. Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 6 weeks for up to 1 year in the	PROCEDURE: Biopsy Undergo biopsy PROCEDURE: Biospecimen Collection Undergo blood sample collection PROCEDURE: Computed Tomography Undergo CT or PET/CT PROCEDURE: Endoscopic Ultrasound Undergo EUS DRUG: Fluorouracil Given IV DRUG: Irinotecan Given IV DRUG: Leucovorin Given IV PROCEDURE: Lymph Node Biopsy Undergo lymph node biopsy PROCEDURE: Magnetic Resonance Imaging Undergo PET/MRI DRUG: Oxaliplatin Given IV BIOLOGICAL: Pembrolizumab Given IV DRUG: Photodynamic Therapy Undergo intratumoral photoradiation PROCEDURE: Positron Emission Tomography Undergo PET/CT and PET/MRI OTHER: Questionnaire Administration Ancillary studies DRUG: Verteporfin Given IV

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Treatment (verteportin, photoradiation, pembrolizumab)

Patients receive verteporfin IV and undergo a biopsy and intratumoral photoradiation over 60-90 minutes using EUS or CT guidance on day 0. Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 6 weeks for up to 1 year in the

PROCEDURE: Biopsy

Undergo biopsy

PROCEDURE: Biospecimen Collection

Undergo blood sample collection

PROCEDURE: Computed Tomography

Undergo CT or PET/CT

PROCEDURE: Endoscopic Ultrasound

Undergo EUS

DRUG: Fluorouracil

Given IV

DRUG: Irinotecan

Given IV

DRUG: Leucovorin

Given IV

PROCEDURE: Lymph Node Biopsy

Undergo lymph node biopsy

PROCEDURE: Magnetic Resonance Imaging

Undergo PET/MRI

DRUG: Oxaliplatin

Given IV

BIOLOGICAL: Pembrolizumab

Given IV

DRUG: Photodynamic Therapy

Undergo intratumoral photoradiation

PROCEDURE: Positron Emission Tomography

Undergo PET/CT and PET/MRI

OTHER: Questionnaire Administration

Ancillary studies

DRUG: Verteporfin

Given IV

Primary Outcome Measures	Measure Description	Time Frame
Overall response rate (ORR)	ORR is defined as the proportion of patients who achieve complete response (CR) or partial response (PR) per immune-modified Response Evaluation Criteria in Solid Tumors (iRECIST) during protocol treatment among evaluable patients.	Up to 2 years

Secondary Outcome Measures	Measure Description	Time Frame
ORR by 1st versus 2nd line therapy	ORR will be reported separately for 1st versus 2nd line therapy groups.	Up to 2 years
Duration of response (DOR)	DOR is defined as the time from the date of first documented CR or PR to the date of first documented disease progression per iRECIST or death due to all causes, whichever occurs first.	Up to 5 years
Progression-free survival (PFS)	PFS is defined as the time from the date of registration to the date of first documented disease progression per iRECIST or death due to all causes, whichever occurs first.	Up to 5 years
Overall survival (OS)	OS is defined as the time from the date of registration to the date of death due to all causes, whichever occurs first.	Up to 5 years
Incidence of adverse events (AEs)	AEs will be graded using the Common Terminology Criteria for Adverse Events version 5.0. AEs and the maximum grade for each type of AE will be summarized for each patient. Frequency tables will be reviewed to determine patterns.	Up to 90 days after last dose of study drug (treatment cycles are usually 29 days)

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Clinical Trials Referral Office

Phone Number: 855-776-0015

Email: mayocliniccancerstudies@mayo.edu

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:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Age ≥ 18 years
Primary tumor histologically or cytologically confirmed (previously biopsied) meta-static, unresectable, or locally advanced pancreatic ductal adenocarcinoma (PDAC), including malignant transformation of a mucinous tumor [intraductal papillary-mucinous neoplasm (IPMN) or mucinous cystic neoplasm (MCN)]

NOTE: Primary tumor in pancreas must still be present to be eligible.
Prior treatment for this pancreatic tumor is allowed as follows:

Up to one line (≤1 regimen) of prior therapy is allowed
No prior treatment with FOLFIRINOX
Measurable disease as defined by iRECIST. NOTE: Tumor lesions in previously irradiated area are considered measurable if previous evidence of progression has been found in these lesions
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
Hemoglobin ≥ 9.0 g/dL (obtained ≤ 15 days prior to registration)
White blood cell (WBC) ≥ 2500/mm^3 (obtained ≤ 15 days prior to registration)
Absolute neutrophil count (ANC) ≥ 1500/mm^3 (obtained ≤ 15 days prior to registration)
Platelet count ≥ 100,000/mm^3 (obtained ≤ 15 days prior to registration)
Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (obtained ≤ 15 days prior to registration)
Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 3 x ULN ( ≥ 5 x ULN for patients with liver involvement) (obtained ≤ 15 days prior to registration)
Prothrombin time (PT) / international normalized ratio (INR) / activated partial thromboplastin time (aPTT) ≤ x ULN (obtained ≤ 15 days prior to registration) OR if patient is receiving anticoagulant therapy then INR or aPTT is within target range of therapy
Creatinine ≤ 1.5 x ULN (obtained ≤ 15 days prior to registration) OR calculated creatinine clearance ≥ 50 ml/min using the Cockcroft-Gault formula
Negative pregnancy test done ≤ 8 days prior to registration, for persons of childbearing potential only
Provide written informed consent
Ability to complete questionnaire(s) by themselves or with assistance
Willingness to provide mandatory blood specimens for correlative research
Willingness to provide mandatory tissue specimens for correlative research
Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)

Any of the following because this study involves an investigational agent, the genotoxic, mutagenic, and teratogenic effects of which on the developing fetus and newborn are unknown:

Pregnant persons
Nursing persons
Persons of childbearing potential and persons able to father a child who are unwilling to employ adequate contraception
Histology or cytology of pancreatic tumor other than adenocarcinoma
Prior treatment:

Received more than one regimen of treatment for pancreatic cancer
Received prior treatment with FOLFIRINOX
History of immunodeficiency illness or immune suppressive medication including systemic steroid therapy or any other form of immunosuppressive therapy ≤ 7 days prior to registration
Failure to recover from acute, reversible effects of prior therapy regardless of interval since last treatment.

EXCEPTION: Grade 1 peripheral (sensory) neuropathy that has been stable for at least 3 months since completion of prior treatment
Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
Known history of human immunodeficiency virus (HIV) infection
Concurrent active hepatitis B (defined as hepatitis B surface antigen [HBsAg] positive and/or detectable hepatitis B virus [HBV] deoxyribonucleic acid [DNA]) and hepatitis C virus (defined as anti-hepatitis C virus [HCV] antibody [Ab] positive and detectable HCV ribonucleic acid [RNA]) infection

EXCEPTIONS:

For patients with evidence of hepatitis B virus (HBV) infection (HBsAg positive), patients must have completed at least 4 weeks of HBV antiviral therapy and the HBV viral load must be undetectable at the time of registration
Patients with a history of hepatitis C virus (HCV) are eligible if they have an undetectable HCV viral load. Patients must have completed curative anti-viral treatment ≥ 4 weeks prior to registration
NOTE: Patients without symptoms or prior history do not require testing prior to registration
History of unstable angina, new onset angina ≤ 3 months prior to registration, myocardial infarction ≤ 6 months prior to registration, or current congestive heart failure New York Heart Association class III or higher
Uncontrolled intercurrent illness including, but not limited to:

Ongoing or active infection
Current diagnosis or previous history of immune-related (non-infectious) pneumonitis or interstitial lung disease that requires or required steroids
Active autoimmune disease that has required systemic treatment ≤ 2 years prior to registration (i.e., with the use of disease-modifying agents, cortico-steroids, or immunosuppressive drugs) NOTE: Replacement therapy (thyroxine, insulin, or physiologic corticosteroid replacement therapy) is allowed
Any condition requiring systemic treatment with either corticosteroids ( > 10 mg daily prednisone equivalents) or other immunosuppressive medications. NOTE: Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
Symptomatic congestive heart failure
Unstable angina pectoris
Cardiac arrhythmia
Or psychiatric illness/social situations that would limit compliance with study requirements
Other active concurrent malignancy

EXCEPTIONS: Non-melanotic skin cancer, carcinoma-in-situ of the cervix, papillary thyroid cancer, or other in situ cancer that has undergone potentially curative therapy
Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

National Cancer Institute (NCI)

Investigators

PRINCIPAL_INVESTIGATOR: Vinay Chandrasekhara, MD, Mayo Clinic in Rochester

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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