Photoradiation With Verteporfin to Facilitate Immunologic Activity of Pembrolizumab in Unresectable, Locally Advanced or Metastatic Pancreatic Cancer
MC230404 Photodynamic Priming to Facilitate Immunologic Activity of Anti-PD1 in Patients With Pancreatic Cancer
Study Overview
Status
Conditions
Intervention / Treatment
- Other: Questionnaire Administration
- Biological: Pembrolizumab
- Procedure: Biospecimen Collection
- Procedure: Biopsy
- Drug: Fluorouracil
- Drug: Leucovorin
- Drug: Oxaliplatin
- Drug: Irinotecan
- Procedure: Magnetic Resonance Imaging
- Procedure: Lymph Node Biopsy
- Drug: Verteporfin
- Procedure: Computed Tomography
- Procedure: Endoscopic Ultrasound
- Drug: Photodynamic Therapy
- Procedure: Positron Emission Tomography
Detailed Description
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Minnesota
-
Rochester, Minnesota, United States, 55905
- Mayo Clinic in Rochester
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
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 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.
|
Ancillary studies
Given IV
Other Names:
Undergo blood sample collection
Other Names:
Undergo biopsy
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given IV
Undergo PET/MRI
Other Names:
Undergo lymph node biopsy
Other Names:
Given IV
Other Names:
Undergo CT or PET/CT
Other Names:
Undergo EUS
Other Names:
Undergo intratumoral photoradiation
Other Names:
Undergo PET/CT and PET/MRI
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Overall response rate (ORR)
Time Frame: Up to 2 years
|
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
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Incidence of adverse events (AEs)
Time Frame: Up to 90 days after last dose of study drug (treatment cycles are usually 29 days)
|
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)
|
|
ORR by 1st versus 2nd line therapy
Time Frame: Up to 2 years
|
ORR will be reported separately for 1st versus 2nd line therapy groups.
|
Up to 2 years
|
|
Duration of response (DOR)
Time Frame: Up to 5 years
|
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)
Time Frame: Up to 5 years
|
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)
Time Frame: Up to 5 years
|
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
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Vinay Chandrasekhara, MD, Mayo Clinic in Rochester
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Endocrine System Diseases
- Neoplasms by Site
- Neoplasms
- Digestive System Neoplasms
- Digestive System Diseases
- Endocrine Gland Neoplasms
- Pancreatic Diseases
- Pancreatic Neoplasms
- Organic Chemicals
- Heterocyclic Compounds, 1-Ring
- Heterocyclic Compounds
- Heterocyclic Compounds, 2-Ring
- Heterocyclic Compounds, Fused-Ring
- Investigative Techniques
- Therapeutics
- Clinical Laboratory Techniques
- Diagnostic Techniques and Procedures
- Diagnosis
- Surgical Procedures, Operative
- Drug Therapy
- Minimally Invasive Surgical Procedures
- Azoles
- Cytological Techniques
- Cytodiagnosis
- Camptothecin
- Alkaloids
- Polycyclic Compounds
- Enzymes and Coenzymes
- Coordination Complexes
- Pyrimidines
- Diagnostic Techniques, Surgical
- Diagnostic Imaging
- Chemistry Techniques, Analytical
- Spectrum Analysis
- Formyltetrahydrofolates
- Tetrahydrofolates
- Folic Acid
- Pterins
- Pteridines
- Uracil
- Pyrimidinones
- Heterocyclic Compounds, 4 or More Rings
- Pyrroles
- Coenzymes
- Macrocyclic Compounds
- Combined Modality Therapy
- Lymph Node Excision
- Ultrasonography
- Biopsy, Fine-Needle
- Biopsy, Needle
- Image-Guided Biopsy
- Ultrasonography, Interventional
- Porphyrins
- Tetrapyrroles
- Verteporfin
- Oxaliplatin
- Irinotecan
- Fluorouracil
- Leucovorin
- Biopsy
- Specimen Handling
- pembrolizumab
- Magnetic Resonance Spectroscopy
- dehydroftorafur
- Sentinel Lymph Node Biopsy
- 1-phenyl-3,3-dimethyltriazene
- Phototherapy
- Endoscopic Ultrasound-Guided Fine Needle Aspiration
- Photochemotherapy
Other Study ID Numbers
- MC230404 (Mayo Clinic)
- P01CA084203 (U.S. NIH Grant/Contract)
- 23-009036 (Other Identifier: Mayo Clinic Institutional Review Board)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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