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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
BioCancell Ltd.
ClinicalTrials.gov Identifier:
NCT00711997
First received: July 8, 2008
Last updated: September 29, 2013
Last verified: September 2013
  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 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by BioCancell Ltd.:

Primary Outcome Measures:
  • Maximal Tolerated Dose (MTD) & Dose Limiting Toxicity (DLT) of Intratumoral Injections of BC-819 [ Time Frame: Week 4 ] [ Designated as safety issue: Yes ]
    Number of Participants Reaching Maximal Tolerated Dose (MTD)


Secondary Outcome Measures:
  • Tumor Response [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    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

  • Tumor Resectability [ Time Frame: 5 to 6 weeks ] [ Designated as safety issue: No ]
    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.


Enrollment: 9
Study Start Date: August 2009
Study Completion Date: December 2010
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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 (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.
  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: NCT00711997

Locations
United States, Maryland
University of Maryland Medical Center
Baltimore, Maryland, United States, 21201-1595
Israel
Hadassah University Hospital
Jerusalem, Israel
Meir Hospital
Kfar Saba, Israel
The Chaim Sheba Medical Center
Tel Hashomer, Israel
Sponsors and Collaborators
BioCancell Ltd.
Investigators
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
  More Information

No publications provided

Responsible Party: BioCancell Ltd.
ClinicalTrials.gov Identifier: NCT00711997     History of Changes
Other Study ID Numbers: BC-07-05
Study First Received: July 8, 2008
Results First Received: August 14, 2012
Last Updated: September 29, 2013
Health Authority: United States: Food and Drug Administration
Israel: Ministry of Health

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

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

ClinicalTrials.gov processed this record on August 19, 2014