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

Study Overview

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

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.

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.

Pancreatic Neoplasms

BIOLOGICAL: DTA-H19

BC-07-05

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2008-07-08	Results First Submitted 2012-08-14	Last Update Submitted that met QC Criteria 2019-03-08
First Submitted that Met QC Criteria 2008-07-08	Results First Submitted that Met QC Criteria 2013-09-29	Last Update Posted (ACTUAL) 2019-03-20
First Posted (ACTUAL) 2008-07-09	Results First Posted 2013-12-02	Last Verified 2019-03

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/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

Participant Group/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

Primary Outcome Measures	Measure Description	Time Frame
Maximal Tolerated Dose (MTD) & Dose Limiting Toxicity (DLT) of Intratumoral Injections of BC-819	If 2 patients in any cohort experience DLTs, then the next lower dose will be considered the MTD if there is a lower dose cohort. A DLT is defined as grade 3 or greater toxicity judged to be at least possibly related to the investigational products.	Week 4

Secondary Outcome Measures	Measure Description	Time Frame
Tumor Response	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	4 weeks
Tumor Resectability	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.	5 to 6 weeks

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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.

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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Abraham Czerniak, MD, The Chaim Sheba Medical Center

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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Clinical Trial Record