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Phase 1/2a DTA-H19 in Patients With UnresectablePancreatic Cancer
This study is not yet open for participant recruitment.
Verified by BioCancell Therapeutics Ltd, January 2009
First Received: July 8, 2008   Last Updated: January 18, 2009   History of Changes
Sponsored by: BioCancell Therapeutics Ltd
Information provided by: BioCancell Therapeutics Ltd
ClinicalTrials.gov Identifier: NCT00711997
  Purpose

This study is designed to assess the safety, tolerability, pharmacokinetics (PK) and preliminary efficacy of DTA-H19 administered intratumorally in patients with unresectable, locally advanced pancreatic cancer. Primary Objective: The primary objective is to determine the maximum tolerated dose (MTD) of intratumoral DTA-H19 and identify any dose limiting toxicities (DLTs). Secondary objectives include determining the adverse events (AEs) profile, effects on clinical laboratory analytes, vital signs, PK, tumor response, and possible tumor resectability after 4 intratumoral administrations of DTA-H19.


Condition Intervention Phase
Pancreatic Neoplasms
Biological: DTA-H19
Phase I
Phase II

MedlinePlus related topics: Cancer Pancreatic Cancer
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Open Label, Dose Comparison, Single Group Assignment, Safety/Efficacy Study
Official Title: Phase 1/2a, Dose-Escalation, Safety, Pharmacokinetic, and Preliminary Efficacy Study of Intratumoral Administration of DTA-H19 in Patients With Unresectable Pancreatic Cancer

Further study details as provided by BioCancell Therapeutics Ltd:

Primary Outcome Measures:
  • Tolerability: The primary safety outcome measure is the MTD. To determine the MTD, DLTs will be assessed in each dose cohort [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Tumor response [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • Tumor resectability [ Time Frame: 5 to 6 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 12
Study Start Date: March 2009
Estimated Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: DTA-H19
    Cohort #1: 4 mg DTA-H19 intratumorally 2 times per week for 2 weeks Cohort #2: 8 mg DTA-H19 intratumorally 2 times per week for 2 weeks
Detailed Description:

DTA-H19, is a doubled stranded DNA plasmid that carries the gene for the diphtheria toxn A (DT-A) chain under the regulation of the H19 promoter sequence. This is a Patient-Oriented, Targeted Therapy as DT-A chain expression is triggered by the presence of H19 transcription factors that are upregulated in tumor cells. The selective initiation of toxin expression results in selective tumor cell destruction via inhibition of protein synthesis in the tumor cell, enabling highly targeted cancer treatment.

  Eligibility

Ages Eligible for Study:   18 Years to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Provide written informed consent and be between the ages of 18 and 79, inclusive.
  • Have unresectable, locally advanced adenocarcinoma of the pancreas proven by biopsy or cytology.
  • Have a target tumor ≤ 6 cm in diameter that is accessible for intratumoral administration by PTA or EUS guidance as determined by the radiologist/gastroenterologist performing the PTA/EUS injection.
  • Have a Karnofsky performance status of ≥ 70%.
  • Have a life expectancy of ≥ 3 months.
  • If female and of child-bearing potential, have a negative serum pregnancy test during screening.
  • Agree to use of a barrier method of contraception if sexually active (both men and women) from the time of administration of the first treatment and for at least 8 weeks after treatment.
  • Have serum creatinine < 2.0 mg/dL, AST and ALT ≥ 2.5 x ULN, PT, PPT, and PT/INR within normal limits, absolute neutrophil count (ANC) > 1,500 x 103 cells/mL, platelets ≥ 100,000/mL, and hemoglobin ≥ 10 mg/dL.
  • Have a biopsy specimen that is positive for H19 expression (grade 2 or greater staining determined by a pathologist).
  • Have screening procedures completed within 4 weeks of starting treatment.
  • No other malignancy present that would interfere with the current intervention.
  • No plans to receive concurrent chemotherapy, hormonal therapy, radiotherapy, immunotherapy or any other type of therapy for treatment of cancer while on this protocol.
  • Have measurable disease.

Exclusion Criteria:

  • Have distant metastatic spread (such as liver or lung metastases), peritoneal spread or malignant ascites.
  • Have prior radiation therapy for pancreatic cancer or radiation to the area of the target tumor field.
  • Endocrine tumors or lymphoma of the pancreas.
  • Have clinically significant pancreatitis within 12 weeks of treatment.
  • If female, be breast feeding.
  • Have a medical condition contraindicated for both percutaneous- and endoscopic- guided delivery or any intercurrent medical illness or other medical condition that would in the judgment of the investigator compromise patient safety or the objectives of the study.
  • Have a history of coagulopathy.
  • Have participated in any therapeutic research study within the last 4 weeks.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00711997

Contacts
Contact: Patricia Ohana, Ph.D 972-2-6585457 pohana@biocancell.com
Contact: Ifat Liven, Msc 972-542404165 ifat.liven@biocancell.com

Locations
United States, Maryland
University of Maryland Medical Center
Baltimore, Maryland, United States, 21201-1595
United States, Virginia
Massey Cancer Center, Virginia Commonwealth University
Richmond, Virginia, United States, 23298-0037
Israel
The Chaim Sheba Medical Center
Tel Hashomer, Israel
Sponsors and Collaborators
BioCancell Therapeutics Ltd
Investigators
Principal Investigator: Abraham Czerniak, MD The Chaim Sheba Medical Center
Principal Investigator: John D Roberts, M.D. Massey Cancer Center
Principal Investigator: Nader Hanna, MD, FACS, FICS University of Maryland Medical Center
  More Information

No publications provided

Responsible Party: BioCancell Therapeutics Ltd ( Patricia Ohana Ph.D. )
Study ID Numbers: BC-07-05
Study First Received: July 8, 2008
Last Updated: January 18, 2009
ClinicalTrials.gov Identifier: NCT00711997     History of Changes
Health Authority: United States: Food and Drug Administration;   Israel: Ministry of Health

Keywords provided by BioCancell Therapeutics Ltd:
H19 gene, plasmid, diphtheria toxin, pancreatic cancer

Study placed in the following topic categories:
Digestive System Diseases
Digestive System Neoplasms
Pancreatic Neoplasms
Endocrine System Diseases
Pancreatic Diseases
Gastrointestinal Neoplasms
Endocrinopathy
Diphtheria
Endocrine Gland Neoplasms

Additional relevant MeSH terms:
Neoplasms
Digestive System Diseases
Neoplasms by Site
Digestive System Neoplasms
Pancreatic Neoplasms
Endocrine System Diseases
Pancreatic Diseases
Endocrine Gland Neoplasms

ClinicalTrials.gov processed this record on May 07, 2009