Phase 1/2a DTA-H19 in Patients With Unresectable Pancreatic Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00711997
Recruitment Status : Completed
First Posted : July 9, 2008
Results First Posted : December 2, 2013
Last Update Posted : December 2, 2013
Information provided by (Responsible Party):
BioCancell Ltd.

Brief Summary:

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 or disease Intervention/treatment Phase
Pancreatic Neoplasms Biological: DTA-H19 Phase 1 Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : August 2009
Actual Primary Completion Date : October 2010
Actual Study Completion Date : December 2010

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: BC-819
Intratumoral administration of BC-819
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
Other Name: BC-819

Primary Outcome Measures :
  1. Maximal Tolerated Dose (MTD) & Dose Limiting Toxicity (DLT) of Intratumoral Injections of BC-819 [ Time Frame: Week 4 ]
    Number of Participants Reaching Maximal Tolerated Dose (MTD)

Secondary Outcome Measures :
  1. Tumor Response [ Time Frame: 4 weeks ]
    Tumor response and progression were defined in accordance with RECIST v. 1.0 and assessed by radiological examination 2 weeks after the end of treatment

  2. Tumor Resectability [ Time Frame: 5 to 6 weeks ]
    The number of subjects in each cohort whose tumor was resectable at the end of the study was to be presented for the ITT and the per-protocol population.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 79 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 (defined as direct extension to the superior mesenteric artery and/or celiac axis with loss of a clear plane between tumor and these arterial structures, or loss of patent superior mesenteric-portal vein confluence). Patients who have been surgically explored and deemed unresectable on that basis are eligible, provided other entry criteria are met. Patients having potentially resectable regional lymph node involvement may be included.
  • 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.
  • Commit to refrain from any concurrent chemotherapy, hormonal therapy, radiotherapy, immunotherapy or any other type of therapy for treatment of cancer while on this protocol, therefore any standard treatment should be postponed while on study.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00711997

United States, Maryland
University of Maryland Medical Center
Baltimore, Maryland, United States, 21201-1595
Hadassah University Hospital
Jerusalem, Israel
Meir Hospital
Kfar Saba, Israel
The Chaim Sheba Medical Center
Tel Hashomer, Israel
Sponsors and Collaborators
BioCancell Ltd.
Principal Investigator: Abraham Czerniak, MD The Chaim Sheba Medical Center
Principal Investigator: Nader Hanna, MD, FACS University of Maryland
Principal Investigator: Fred Konikoff, MD Meir Medical Center
Principal Investigator: Ayala Hubert, MD Hadassah University Hospital

Responsible Party: BioCancell Ltd. Identifier: NCT00711997     History of Changes
Other Study ID Numbers: BC-07-05
First Posted: July 9, 2008    Key Record Dates
Results First Posted: December 2, 2013
Last Update Posted: December 2, 2013
Last Verified: September 2013

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

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