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

NCT ID: NCT06381154

Last Updated: 2026-01-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

25 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-12-06

Study Completion Date

2029-12-06

Brief Summary

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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.

Detailed Description

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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.

Conditions

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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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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 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, PET/CT and optional PET/MRI on study.

Group Type EXPERIMENTAL

Biopsy

Intervention Type PROCEDURE

Undergo biopsy

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Computed Tomography

Intervention Type PROCEDURE

Undergo CT or PET/CT

Endoscopic Ultrasound

Intervention Type PROCEDURE

Undergo EUS

Fluorouracil

Intervention Type DRUG

Given IV

Irinotecan

Intervention Type DRUG

Given IV

Leucovorin

Intervention Type DRUG

Given IV

Lymph Node Biopsy

Intervention Type PROCEDURE

Undergo lymph node biopsy

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo PET/MRI

Oxaliplatin

Intervention Type DRUG

Given IV

Pembrolizumab

Intervention Type BIOLOGICAL

Given IV

Photodynamic Therapy

Intervention Type DRUG

Undergo intratumoral photoradiation

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET/CT and PET/MRI

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Verteporfin

Intervention Type DRUG

Given IV

Interventions

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Biopsy

Undergo biopsy

Intervention Type PROCEDURE

Biospecimen Collection

Undergo blood sample collection

Intervention Type PROCEDURE

Computed Tomography

Undergo CT or PET/CT

Intervention Type PROCEDURE

Endoscopic Ultrasound

Undergo EUS

Intervention Type PROCEDURE

Fluorouracil

Given IV

Intervention Type DRUG

Irinotecan

Given IV

Intervention Type DRUG

Leucovorin

Given IV

Intervention Type DRUG

Lymph Node Biopsy

Undergo lymph node biopsy

Intervention Type PROCEDURE

Magnetic Resonance Imaging

Undergo PET/MRI

Intervention Type PROCEDURE

Oxaliplatin

Given IV

Intervention Type DRUG

Pembrolizumab

Given IV

Intervention Type BIOLOGICAL

Photodynamic Therapy

Undergo intratumoral photoradiation

Intervention Type DRUG

Positron Emission Tomography

Undergo PET/CT and PET/MRI

Intervention Type PROCEDURE

Questionnaire Administration

Ancillary studies

Intervention Type OTHER

Verteporfin

Given IV

Intervention Type DRUG

Other Intervention Names

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BIOPSY_TYPE Bx Biological Sample Collection Biospecimen Collected Specimen Collection CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized axial tomography (procedure) Computerized Tomography Computerized Tomography (CT) scan CT CT Scan tomography endosonography EUS 5 Fluorouracil 5 Fluorouracilum 5 FU 5-Fluoro-2,4(1H, 3H)-pyrimidinedione 5-Fluorouracil 5-Fluracil 5-Fu 5FU AccuSite Carac Fluoro Uracil Fluouracil Flurablastin Fluracedyl Fluracil Fluril Fluroblastin Ribofluor Ro 2-9757 Ro-2-9757 Folinic acid Biopsy of Lymph Node Magnetic Resonance Magnetic Resonance Imaging (MRI) Magnetic resonance imaging (procedure) Magnetic Resonance Imaging Scan Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance MR MR Imaging MRI MRI Scan MRIs NMR Imaging NMRI Nuclear Magnetic Resonance Imaging sMRI Structural MRI 1-OHP Ai Heng Aiheng Dacotin Dacplat Diaminocyclohexane Oxalatoplatinum Eloxatin Eloxatine JM-83 Oxalatoplatin Oxalatoplatinum RP 54780 RP-54780 SR-96669 Elplat JM83 RP54780 SR96669 BCD-201 Keytruda Lambrolizumab MK-3475 Pembrolizumab Biosimilar BCD-201 SCH 900475 MK3475 GME751 GME 751 Pembrolizumab Biosimilar GME751 Pembrolizumab Biosimilar QL2107 Pembrolizumab Biosimilar RPH-075 Pembrolizumab Biosimilar SB27 PDT Photoradiation Therapy Medical Imaging, Positron Emission Tomography PET PET Scan Positron emission tomography (procedure) Positron Emission Tomography Scan Positron-Emission Tomography PT Benzoporphyrin Derivative Monoacid Ring A BPD-MA Visudyne

Eligibility Criteria

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Inclusion Criteria

* 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)

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Mayo Clinic

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Vinay Chandrasekhara, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic in Rochester

Locations

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Mayo Clinic in Rochester

Rochester, Minnesota, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Clinical Trials Referral Office

Role: CONTACT

855-776-0015

Facility Contacts

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Clinical Trials Referral Office

Role: primary

855-776-0015

Related Links

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Other Identifiers

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NCI-2024-03078

Identifier Type: REGISTRY

Identifier Source: secondary_id

23-009036

Identifier Type: OTHER

Identifier Source: secondary_id

MC230404

Identifier Type: OTHER

Identifier Source: secondary_id

P01CA084203

Identifier Type: NIH

Identifier Source: secondary_id

View Link

MC230404

Identifier Type: -

Identifier Source: org_study_id

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