Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Indiana University
Sponsor:
Collaborators:
American Society for Gastrointestinal Endoscopy
Pinnacle Biologics Inc.
Information provided by (Responsible Party):
Indiana University
ClinicalTrials.gov Identifier:
NCT01770132
First received: January 15, 2013
Last updated: May 30, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Acinar Cell Adenocarcinoma of the Pancreas
Duct Cell Adenocarcinoma of the Pancreas
Stage III Pancreatic Cancer
Drug: porfimer sodium
Procedure: endoscopic ultrasonography
Procedure: photodynamic therapy
Drug: gemcitabine hydrochloride
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Indiana University:

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 [ Time Frame: Up to 4 years ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Week 2 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
  • Surgical downstaging off of abdominal vessels or change in tumor unresectability [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
  • Change in CA 19-9 levels [ Time Frame: Baseline to up to 4 years ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    A Kaplan-Meier plot will be produced.

  • Overall survival [ 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 ] [ Designated as safety issue: No ]
    A Kaplan-Meier plot will be produced.


Estimated Enrollment: 12
Study Start Date: April 2013
Estimated Study Completion Date: January 2018
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: porfimer sodium, EUS-PDT, gemcitabine
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.
Drug: porfimer sodium
Given IV
Other Names:
  • Photofrin
  • Photofrin II
  • Porfimer
Procedure: endoscopic ultrasonography
Undergo EUS-PDT
Other Names:
  • endoscopic ultrasound
  • EUS
Procedure: photodynamic therapy
Undergo EUS-PDT
Other Names:
  • Light Infusion Therapy
  • PDT
  • therapy, photodynamic
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • gemcitabine
  • Gemzar
  • LY-188011

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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01770132

Contacts
Contact: Janet R Flynn, BSN 317-274-0972 janflynn@iupui.edu
Contact: John M DeWitt, MD 317-944-1113 jodewitt@iupui.edu

Locations
United States, Indiana
IU Simon Cancer Center Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Janet R Flynn, BSN    317-274-0972    janflynn@iupui.edu   
Principal Investigator: John M DeWitt, MD         
Sponsors and Collaborators
Indiana University
American Society for Gastrointestinal Endoscopy
Pinnacle Biologics Inc.
Investigators
Principal Investigator: John M DeWitt, MD Indiana University
  More Information

No publications provided

Responsible Party: Indiana University
ClinicalTrials.gov Identifier: NCT01770132     History of Changes
Other Study ID Numbers: IUCRO-0319, 1207009096
Study First Received: January 15, 2013
Last Updated: May 30, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration
United States: Data and Safety Monitoring Board

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Endocrine Gland Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Pancreatic Diseases
Adenocarcinoma
Carcinoma, Acinar Cell
Carcinoma
Digestive System Diseases
Endocrine System Diseases
Dihematoporphyrin Ether
Gemcitabine
Hematoporphyrin Derivative
Trioxsalen
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Dermatologic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Photosensitizing Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 27, 2014