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

Phase 1/2a, Dose-Escalation, Safety, Pharmacokinetic, and Preliminary Efficacy Study of Intratumoral Administration of 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.

Study Overview

• Status: Completed
• Conditions: Pancreatic Neoplasms
• Intervention / Treatment: Biological: DTA-H19

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
• Enrollment (Actual): 9
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Israel
  • Jerusalem, Israel
    • Hadassah University Hospital
  • Kfar Saba, Israel
    • Meir Hospital
  • Tel Hashomer, Israel
    • The Chaim Sheba Medical Center
• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201-1595
      • University of Maryland Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

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; Other Names: BC-819

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Anchiano Therapeutics Israel 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

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (ACTUAL): October 1, 2010
• Study Completion (ACTUAL): December 1, 2010

Study Registration Dates

• First Submitted: July 8, 2008
• First Submitted That Met QC Criteria: July 8, 2008
• First Posted (ESTIMATE): July 9, 2008

Study Record Updates

• Last Update Posted (ACTUAL): March 20, 2019
• Last Update Submitted That Met QC Criteria: March 8, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: inodiftagene vixteplasmid; H19 gene, plasmid, diphtheria toxin, pancreatic cancer; BC-819
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: BC-07-05