search
Back to results

Ultrasound-Guided Photodynamic Therapy With Photofrin & Gemcitabine for Patients With Locally Advanced Pancreatic Cancer

Primary Purpose

Acinar Cell Adenocarcinoma of the Pancreas, Duct Cell Adenocarcinoma of the Pancreas, Stage III Pancreatic Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
porfimer sodium
endoscopic ultrasonography
photodynamic therapy
gemcitabine hydrochloride
Sponsored by
John DeWitt
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acinar Cell Adenocarcinoma of the Pancreas

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Unresectable, locally advanced measurable (at least bidirectional) adenocarcinoma of the pancreas (regardless of site) proven by biopsy or cytology and confirmed by surgical consultation
  • Informed consent and authorization for the release of health information signed by the patient
  • Karnofsky performance status >= 70%
  • Life expectancy >= 3 months
  • Females of childbearing potential and males must use an effective method of contraception

Exclusion Criteria:

  • Metastatic (stage IV) disease (including involvement of the colon, adrenals, or kidney, or radiographic evidence of peritoneal seeding or pulmonary metastases)
  • Previous chemotherapy, radiotherapy of other treatment for PC
  • Gastric or duodenal wall invasion by the primary PC as assessed by CT or MRI and EUS staging
  • Gastric or duodenal ulcer (at least 10 mm in size) within 10 mm of expected endoscopy puncture site(s) for PDT
  • Esophageal or gastric varices
  • Cystic component >= 25% the total volume of the tumor
  • Ascites detected by CT, ultrasound (US) or MRI; (trace ascites will not be an exclusion)
  • Bulky celiac adenopathy (i.e., >= 2.5 cm in diameter)
  • Diagnosis of islet cell tumor, lymphoma, metastatic lesion, acinar cell (or other atypical pathologic malignancy)
  • History of other malignancy in the past 2 years except carcinoma in situ of the cervix or bladder, non-melanomatous skin cancer or localized/early stage prostate cancer
  • Unable to receive or previously intolerant of moderate and/or deep sedation
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >= 3 x upper limit of normal (ULN)
  • Total bilirubin >= 3 x ULN
  • Alkaline phosphatase >= 3 x ULN
  • International normalized ratio (INR) >= 1.5
  • Partial thromboplastin time (PTT) ratio >= 1.5
  • Serum creatinine >= 2.0 mg/dL
  • Hematocrit =< 28% or hemoglobin =< 9 g/dL, but may have red blood cell (RBC) transfusion
  • Platelet count =< 100,000/microliter (uL)
  • Absolute neutrophil count (ANC) =< 1500/uL
  • Clinically significant pancreatitis within 12 weeks of treatment with protocol therapy
  • Contraindication to EUS-guided needle puncture into the pancreas
  • History of coagulopathy or known thrombophilias
  • Use of anticoagulants that cannot be discontinued both 5 days before and 5 days after EUS
  • Clinical evidence of active infection of any type, including hepatitis B or C virus
  • Pregnant or lactating women
  • Experimental medications within the last 4 weeks prior to day 1
  • Any surgery (including diagnostic laparoscopy and/or biliary +/- duodenal palliative bypass for inoperable PC) within the 2 weeks prior to day 1 of study protocol
  • Chronic systemic corticosteroid use at superphysiologic doses (>= 10 mg prednisone per day or equivalent)
  • Inability to avoid exposure of skin or eyes to direct sunlight or bright indoor light for at least 30 days
  • Porphyria
  • Inability to obtain venous access in the antecubital region to administer PHO or sedation for endoscopy procedures
  • Significant concurrent medical or psychiatric illness which, in the opinion of the principal investigator would interfere with trial participation

Sites / Locations

  • IU Simon Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

porfimer sodium, EUS-PDT, gemcitabine

Arm Description

Patients receive porfimer sodium IV over 3-5 minutes on day 1 and undergo endoscopic ultrasonography-photodynamic therapy (EUS-PDT) on days 1, 3, 8, and 21. After completion of EUS-PDT, patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 of courses 1 and 2 and on day 22 of courses 3 and 5. During courses 1-5, treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. After course 5, treatment with gemcitabine hydrochloride repeats every 2 months in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Evaluate the number of subjects with adverse events which occur when up to 3 sites within the pancreas are treated with PDT using a total dose of 50 or 100 J per site
Adverse events will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0 which uses a scale of 1 (mild) to 5 (caused death).

Secondary Outcome Measures

CT- or MRI-detected volume of tumor necrosis
Will be compared using paired t-tests or Wilcoxon rank sum tests as appropriate and changes will be plotted by maximal total energy of treatment to explore for dose-response effects.
Rates of tumor size stabilization or decease by EUS-PDT
Will be compared using paired t-tests or Wilcoxon rank sum tests as appropriate and changes will be plotted by maximal total energy of treatment to explore for dose-response effects.
Objective response rate per RECIST
Surgical downstaging off of abdominal vessels or change in tumor unresectability
Change in CA 19-9 levels
Will be compared using paired t-tests or Wilcoxon rank sum tests as appropriate and changes will be plotted by maximal total energy of treatment to explore for dose-response effects.
Progression-free survival
A Kaplan-Meier plot will be produced.
Overall survival
A Kaplan-Meier plot will be produced.

Full Information

First Posted
January 15, 2013
Last Updated
December 11, 2018
Sponsor
John DeWitt
Collaborators
American Society for Gastrointestinal Endoscopy, Pinnacle Biologics Inc.
search

1. Study Identification

Unique Protocol Identification Number
NCT01770132
Brief Title
Ultrasound-Guided Photodynamic Therapy With Photofrin & Gemcitabine for Patients With Locally Advanced Pancreatic Cancer
Official Title
Open-label, Single-center, Non-randomized, Phase I, Dose-ranging Study of Endoscopic Ultrasound (EUS) Guided Photodynamic Therapy (PDT) With Photofrin® in Locally Advanced Pancreatic Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
December 2018
Overall Recruitment Status
Completed
Study Start Date
April 19, 2013 (Actual)
Primary Completion Date
July 13, 2017 (Actual)
Study Completion Date
October 28, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
John DeWitt
Collaborators
American Society for Gastrointestinal Endoscopy, Pinnacle Biologics Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase I trial studies the side effects and best dose of ultrasound-guided photodynamic therapy with porfimer sodium when given together with gemcitabine hydrochloride in treating patients with locally advanced pancreatic cancer. Photodynamic therapy uses a drug, porfimer sodium, that becomes active when it is exposed to a certain kind of light. When the drug is active, cancer cells are killed. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving photodynamic therapy together with gemcitabine hydrochloride may be effect in patients with pancreatic cancer.
Detailed Description
PRIMARY OBJECTIVES: I. To determine the safety of increasing porfimer sodium (PHO) dose and total energy by endoscopic ultrasound (EUS)-guided photodynamic therapy (PDT) for locally advanced unresectable pancreatic cancer (PC) in humans. SECONDARY OBJECTIVES: I. Quantify computed tomography (CT) detected volume of tumor necrosis produced by EUS-PDT. II. Quantify rates of tumor size stabilization or decrease by EUS PDT and determine objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) criteria. III. Determine surgical downstaging off of abdominal vessels and resectability. IV. Determine changes in serum cancer antigen (CA) 19-9 levels with treatment. V. Evaluate progression-free and overall survival. OUTLINE: This is a dose-escalation study of EUS-PDT with porfimer sodium. Patients receive porfimer sodium intravenously (IV) on day 1 and undergo EUS-PDT on days 1, 3, 8, and 21. After completion of EUS-PDT, patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 of courses 1 and 2 and on day 22 of courses 3 and 5. During courses 1-5, treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. After course 5, treatment with gemcitabine hydrochloride repeats every 2 months in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acinar Cell Adenocarcinoma of the Pancreas, Duct Cell Adenocarcinoma of the Pancreas, Stage III Pancreatic Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
porfimer sodium, EUS-PDT, gemcitabine
Arm Type
Experimental
Arm Description
Patients receive porfimer sodium IV over 3-5 minutes on day 1 and undergo endoscopic ultrasonography-photodynamic therapy (EUS-PDT) on days 1, 3, 8, and 21. After completion of EUS-PDT, patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 of courses 1 and 2 and on day 22 of courses 3 and 5. During courses 1-5, treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. After course 5, treatment with gemcitabine hydrochloride repeats every 2 months in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
porfimer sodium
Other Intervention Name(s)
Photofrin, Photofrin II, Porfimer
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
endoscopic ultrasonography
Other Intervention Name(s)
endoscopic ultrasound, EUS
Intervention Description
Undergo EUS-PDT
Intervention Type
Procedure
Intervention Name(s)
photodynamic therapy
Other Intervention Name(s)
Light Infusion Therapy, PDT, therapy, photodynamic
Intervention Description
Undergo EUS-PDT
Intervention Type
Drug
Intervention Name(s)
gemcitabine hydrochloride
Other Intervention Name(s)
gemcitabine, Gemzar, LY-188011
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Evaluate the number of subjects with adverse events which occur when up to 3 sites within the pancreas are treated with PDT using a total dose of 50 or 100 J per site
Description
Adverse events will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0 which uses a scale of 1 (mild) to 5 (caused death).
Time Frame
Up to 4 years
Secondary Outcome Measure Information:
Title
CT- or MRI-detected volume of tumor necrosis
Description
Will be compared using paired t-tests or Wilcoxon rank sum tests as appropriate and changes will be plotted by maximal total energy of treatment to explore for dose-response effects.
Time Frame
Week 2
Title
Rates of tumor size stabilization or decease by EUS-PDT
Description
Will be compared using paired t-tests or Wilcoxon rank sum tests as appropriate and changes will be plotted by maximal total energy of treatment to explore for dose-response effects.
Time Frame
Up to 4 years
Title
Objective response rate per RECIST
Time Frame
Up to 4 years
Title
Surgical downstaging off of abdominal vessels or change in tumor unresectability
Time Frame
Up to 4 years
Title
Change in CA 19-9 levels
Description
Will be compared using paired t-tests or Wilcoxon rank sum tests as appropriate and changes will be plotted by maximal total energy of treatment to explore for dose-response effects.
Time Frame
Baseline to up to 4 years
Title
Progression-free survival
Description
A Kaplan-Meier plot will be produced.
Time Frame
From the date of initial treatment to the earliest date of disease progression, resection of measurable tumor or death for patients who fail; and to the date of disease evaluation for patients who remain at risk for failure, assessed up to 4 years
Title
Overall survival
Description
A Kaplan-Meier plot will be produced.
Time Frame
From the day of first treatment to the earlier of death (from any cause) and the last date of patient contact, assessed up to 4 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Unresectable, locally advanced measurable (at least bidirectional) adenocarcinoma of the pancreas (regardless of site) proven by biopsy or cytology and confirmed by surgical consultation Informed consent and authorization for the release of health information signed by the patient Karnofsky performance status >= 70% Life expectancy >= 3 months Females of childbearing potential and males must use an effective method of contraception Exclusion Criteria: Metastatic (stage IV) disease (including involvement of the colon, adrenals, or kidney, or radiographic evidence of peritoneal seeding or pulmonary metastases) Previous chemotherapy, radiotherapy of other treatment for PC Gastric or duodenal wall invasion by the primary PC as assessed by CT or MRI and EUS staging Gastric or duodenal ulcer (at least 10 mm in size) within 10 mm of expected endoscopy puncture site(s) for PDT Esophageal or gastric varices Cystic component >= 25% the total volume of the tumor Ascites detected by CT, ultrasound (US) or MRI; (trace ascites will not be an exclusion) Bulky celiac adenopathy (i.e., >= 2.5 cm in diameter) Diagnosis of islet cell tumor, lymphoma, metastatic lesion, acinar cell (or other atypical pathologic malignancy) History of other malignancy in the past 2 years except carcinoma in situ of the cervix or bladder, non-melanomatous skin cancer or localized/early stage prostate cancer Unable to receive or previously intolerant of moderate and/or deep sedation Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >= 3 x upper limit of normal (ULN) Total bilirubin >= 3 x ULN Alkaline phosphatase >= 3 x ULN International normalized ratio (INR) >= 1.5 Partial thromboplastin time (PTT) ratio >= 1.5 Serum creatinine >= 2.0 mg/dL Hematocrit =< 28% or hemoglobin =< 9 g/dL, but may have red blood cell (RBC) transfusion Platelet count =< 100,000/microliter (uL) Absolute neutrophil count (ANC) =< 1500/uL Clinically significant pancreatitis within 12 weeks of treatment with protocol therapy Contraindication to EUS-guided needle puncture into the pancreas History of coagulopathy or known thrombophilias Use of anticoagulants that cannot be discontinued both 5 days before and 5 days after EUS Clinical evidence of active infection of any type, including hepatitis B or C virus Pregnant or lactating women Experimental medications within the last 4 weeks prior to day 1 Any surgery (including diagnostic laparoscopy and/or biliary +/- duodenal palliative bypass for inoperable PC) within the 2 weeks prior to day 1 of study protocol Chronic systemic corticosteroid use at superphysiologic doses (>= 10 mg prednisone per day or equivalent) Inability to avoid exposure of skin or eyes to direct sunlight or bright indoor light for at least 30 days Porphyria Inability to obtain venous access in the antecubital region to administer PHO or sedation for endoscopy procedures Significant concurrent medical or psychiatric illness which, in the opinion of the principal investigator would interfere with trial participation
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John M DeWitt, MD
Organizational Affiliation
Indiana University
Official's Role
Principal Investigator
Facility Information:
Facility Name
IU Simon Cancer Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
30222972
Citation
DeWitt JM, Sandrasegaran K, O'Neil B, House MG, Zyromski NJ, Sehdev A, Perkins SM, Flynn J, McCranor L, Shahda S. Phase 1 study of EUS-guided photodynamic therapy for locally advanced pancreatic cancer. Gastrointest Endosc. 2019 Feb;89(2):390-398. doi: 10.1016/j.gie.2018.09.007. Epub 2018 Sep 14.
Results Reference
derived

Learn more about this trial

Ultrasound-Guided Photodynamic Therapy With Photofrin & Gemcitabine for Patients With Locally Advanced Pancreatic Cancer

We'll reach out to this number within 24 hrs