Trial Title:
Photoradiation With Verteporfin to Facilitate Immunologic Activity of Pembrolizumab in Unresectable, Locally Advanced or Metastatic Pancreatic Cancer
NCT ID:
NCT06381154
Condition:
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
Conditions: Official terms:
Adenocarcinoma
Pancreatic Neoplasms
Leucovorin
Pembrolizumab
Oxaliplatin
Fluorouracil
Irinotecan
Verteporfin
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biopsy
Description:
Undergo biopsy
Arm group label:
Treatment (verteportin, photoradiation, pembrolizumab)
Other name:
BIOPSY_TYPE
Other name:
Bx
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Treatment (verteportin, photoradiation, pembrolizumab)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT or PET/CT
Arm group label:
Treatment (verteportin, photoradiation, pembrolizumab)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
Computerized Tomography (CT) scan
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Procedure
Intervention name:
Endoscopic Ultrasound
Description:
Undergo EUS
Arm group label:
Treatment (verteportin, photoradiation, pembrolizumab)
Other name:
endosonography
Other name:
EUS
Intervention type:
Drug
Intervention name:
Fluorouracil
Description:
Given IV
Arm group label:
Treatment (verteportin, photoradiation, pembrolizumab)
Other name:
5 Fluorouracil
Other name:
5 Fluorouracilum
Other name:
5 FU
Other name:
5-Fluoro-2,4(1H, 3H)-pyrimidinedione
Other name:
5-Fluorouracil
Other name:
5-Fluracil
Other name:
5-Fu
Other name:
5FU
Other name:
AccuSite
Other name:
Carac
Other name:
Fluoro Uracil
Other name:
Fluouracil
Other name:
Flurablastin
Other name:
Fluracedyl
Other name:
Fluracil
Other name:
Fluril
Other name:
Fluroblastin
Other name:
Ribofluor
Other name:
Ro 2-9757
Other name:
Ro-2-9757
Intervention type:
Drug
Intervention name:
Irinotecan
Description:
Given IV
Arm group label:
Treatment (verteportin, photoradiation, pembrolizumab)
Intervention type:
Drug
Intervention name:
Leucovorin
Description:
Given IV
Arm group label:
Treatment (verteportin, photoradiation, pembrolizumab)
Other name:
Folinic acid
Intervention type:
Procedure
Intervention name:
Lymph Node Biopsy
Description:
Undergo lymph node biopsy
Arm group label:
Treatment (verteportin, photoradiation, pembrolizumab)
Other name:
Biopsy of Lymph Node
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo PET/MRI
Arm group label:
Treatment (verteportin, photoradiation, pembrolizumab)
Other name:
Magnetic Resonance
Other name:
Magnetic Resonance Imaging (MRI)
Other name:
Magnetic resonance imaging (procedure)
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
MRIs
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Other name:
sMRI
Other name:
Structural MRI
Intervention type:
Drug
Intervention name:
Oxaliplatin
Description:
Given IV
Arm group label:
Treatment (verteportin, photoradiation, pembrolizumab)
Other name:
1-OHP
Other name:
Ai Heng
Other name:
Aiheng
Other name:
Dacotin
Other name:
Dacplat
Other name:
Diaminocyclohexane Oxalatoplatinum
Other name:
Eloxatin
Other name:
Eloxatine
Other name:
JM-83
Other name:
Oxalatoplatin
Other name:
Oxalatoplatinum
Other name:
RP 54780
Other name:
RP-54780
Other name:
SR-96669
Intervention type:
Biological
Intervention name:
Pembrolizumab
Description:
Given IV
Arm group label:
Treatment (verteportin, photoradiation, pembrolizumab)
Other name:
BCD-201
Other name:
Keytruda
Other name:
Lambrolizumab
Other name:
MK-3475
Other name:
Pembrolizumab Biosimilar BCD-201
Other name:
SCH 900475
Intervention type:
Drug
Intervention name:
Photodynamic Therapy
Description:
Undergo intratumoral photoradiation
Arm group label:
Treatment (verteportin, photoradiation, pembrolizumab)
Other name:
PDT
Other name:
Photoradiation Therapy
Intervention type:
Procedure
Intervention name:
Positron Emission Tomography
Description:
Undergo PET/CT and PET/MRI
Arm group label:
Treatment (verteportin, photoradiation, pembrolizumab)
Other name:
Medical Imaging, Positron Emission Tomography
Other name:
PET
Other name:
PET Scan
Other name:
Positron emission tomography (procedure)
Other name:
Positron Emission Tomography Scan
Other name:
Positron-Emission Tomography
Other name:
proton magnetic resonance spectroscopic imaging
Other name:
PT
Intervention type:
Other
Intervention name:
Questionnaire Administration
Description:
Ancillary studies
Arm group label:
Treatment (verteportin, photoradiation, pembrolizumab)
Intervention type:
Drug
Intervention name:
Verteporfin
Description:
Given IV
Arm group label:
Treatment (verteportin, photoradiation, pembrolizumab)
Other name:
Benzoporphyrin Derivative Monoacid Ring A
Other name:
BPD-MA
Other name:
Visudyne
Summary:
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:
PRIMARY OBJECTIVE:
I. To evaluate overall response rate (ORR) per immune-mediated Response Evaluation
Criteria in Solid Tumors (iRECIST) criteria in patients with unresectable pancreatic
ductal adenocarcinoma (PDAC) who have failed first line treatment treated with the
combination photodynamic priming (PDP) and pembrolizumab.
SECONDARY OBJECTIVES:
I. To evaluate duration of response (DOR) per iRECIST criteria in patients treated with
the combination of PDP and pembrolizumab.
II. To evaluate progression-free survival (PFS) per iRECIST criteria in patients treated
with the combination of PDP and pembrolizumab.
III. To evaluate overall survival (OS) in patients treated with the combination of PDP
and pembrolizumab.
IV. 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.
Criteria for eligibility:
Criteria:
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)]
- 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
- 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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Mayo Clinic in Rochester
Address:
City:
Rochester
Zip:
55905
Country:
United States
Contact:
Last name:
Clinical Trials Referral Office
Phone:
855-776-0015
Email:
mayocliniccancerstudies@mayo.edu
Investigator:
Last name:
Vinay Chandrasekhara, M.D.
Email:
Principal Investigator
Start date:
October 30, 2024
Completion date:
October 4, 2029
Lead sponsor:
Agency:
Mayo Clinic
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
Mayo Clinic
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06381154
https://www.mayo.edu/research/clinical-trials
