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

Sponsor

John DeWitt (Other)

Overall Status

Completed

CT.gov ID

NCT01770132

Collaborator

American Society for Gastrointestinal Endoscopy (Other), Pinnacle Biologics Inc. (Industry)

Enrollment

Location

Arm

66.3

Actual Duration (Months)

0.2

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	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

Detailed Description

PRIMARY OBJECTIVES:

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:

Quantify computed tomography (CT) detected volume of tumor necrosis produced by EUS-PDT.
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.
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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

12 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (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

Actual Study Start Date :

Apr 19, 2013

Actual Primary Completion Date :

Jul 13, 2017

Actual Study Completion Date :

Oct 28, 2018

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

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 [Up to 4 years]
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 [Week 2]
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 [Up to 4 years]
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 [Up to 4 years]
Surgical downstaging off of abdominal vessels or change in tumor unresectability [Up to 4 years]
Change in CA 19-9 levels [Baseline to up to 4 years]
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 [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]
A Kaplan-Meier plot will be produced.
Overall survival [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]
A Kaplan-Meier plot will be produced.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts 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