Efficacy And Safety Of BC-819 And Gemcitabine In Patients With Locally Advanced Pancreatic Adenocarcinoma

Study Overview

Efficacy and Safety of BC-819 and Gemcitabine in Patients With Locally Advanced Pancreatic Adenocarcinoma

This is a multicenter, open label, randomized, phase 2b study, designed to evaluate the safety and efficacy of patients with locally advanced pancreatic adenocarcinoma following intratumoral administration of BC-819 and intravenously administered gemcitabine. Intratumoral injections of BC-819 will be performed using endoscopic ultrasound (EUS). Primary Objective: To assess the effect of intratumoral endoscopic ultrasound injection of BC-819 administered with intravenous gemcitabine on progression-free survival. Secondary Objectives: To compare the effects of intratumoral injection of BC-819 administered in combination with intravenous gemcitabine vs. intravenous gemcitabine alone on: Overall survival, Response rate, Resectability of the target tumor lesion, Quality of life, Safety, Serological Tumor Marker: CA 19-9, Duration of response, Failure-free survival

BC-819 (also known as DTA-H19) is a double-stranded DNA plasmid, 4,560 base pairs (bp) in length, carrying the gene for the Diphtheria toxin A (DT-A) chain under the regulation of the H19 promoter. This is a Targeted Cancer Therapy; DT-A chain expression is triggered by the presence of H19 transcription factors that are only up-regulated in tumor cells. The selective initiation of toxin expression results in selective tumor cell destruction via inhibition of protein synthesis selectively in the tumor cell, enabling highly targeted cancer treatment.

Pancreas, Adenocarcinoma

BIOLOGICAL: Biological/Vaccine: BC-819

BC-PAN-02

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 2011-08-08	Results First Submitted 2019-07-31	Last Update Submitted that met QC Criteria 2019-10-14
First Submitted that Met QC Criteria 2011-08-09	Results First Submitted that Met QC Criteria 2019-10-14	Last Update Posted (ACTUAL) 2019-11-01
First Posted (ACTUAL) 2011-08-10	Results First Posted 2019-11-01	Last Verified 2019-10

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:
Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: 8 mg BC-819 and Gemcitabine gemcitabine dose of 1000mg/m2 + 8 mg of BC-819	BIOLOGICAL: Biological/Vaccine: BC-819 Post screening and prior to randomization, all patients will receive gemcitabine by IV infusion at a dose of 1000mg/m2 once weekly for four weeks. They may also enter the study if they received up to 4 doses of gemcitabine before entering the study. In th
EXPERIMENTAL: 12 mg BC-819 and Gemcitabine gemcitabine dose of 1000mg/m2 + 12 mg of BC-819	BIOLOGICAL: Biological/Vaccine: BC-819 Post screening and prior to randomization, all patients will receive gemcitabine by IV infusion at a dose of 1000mg/m2 once weekly for four weeks. They may also enter the study if they received up to 4 doses of gemcitabine before entering the study. In th

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: 8 mg BC-819 and Gemcitabine

gemcitabine dose of 1000mg/m2 + 8 mg of BC-819

BIOLOGICAL: Biological/Vaccine: BC-819

Post screening and prior to randomization, all patients will receive gemcitabine by IV infusion at a dose of 1000mg/m2 once weekly for four weeks. They may also enter the study if they received up to 4 doses of gemcitabine before entering the study. In th

EXPERIMENTAL: 12 mg BC-819 and Gemcitabine

gemcitabine dose of 1000mg/m2 + 12 mg of BC-819

BIOLOGICAL: Biological/Vaccine: BC-819

Post screening and prior to randomization, all patients will receive gemcitabine by IV infusion at a dose of 1000mg/m2 once weekly for four weeks. They may also enter the study if they received up to 4 doses of gemcitabine before entering the study. In th

Primary Outcome Measures	Measure Description	Time Frame
Progression-free Survival (PFS)	To compare the effect of intratumoral endoscopic ultrasound injection of BC-819 administered with intravenous gemcitabine on progression-free survival. PFS was defined as the time from the date of consent until objective tumor progression or death. Median PFS by Kaplan-Meier analysis was used for evaluation. The target tumor lesion was identified and the longest diameter of the target lesion was measured according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines. For disease evaluations after treatment, scans conducted at baseline that were used for tumor measurements were repeated.	24 months

Secondary Outcome Measures	Measure Description	Time Frame
Overall Survival (OS)	OS was calculated from the date of consent until death due to any cause.	24 months
Response Rate of Target Lesion	Response rate will be assessed both for the primary target tumor lesion alone and overall, including development of metastases. Target tumor lesions are identified and the longest diameter of the target lesion is measured by the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines. Complete response: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also show an increase of at least 5 mm. Stable Disease: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.	8 weeks
Resectability of the Target Tumor Lesion	Resectability of the target tumor lesion was determined by CT/MRI as defined in the National Comprehensive Cancer network (NCCN) guidelines. Resectable tumors have no arterial tumor contact (celiac axis [CA], superior mesenteric artery [SMA], or common hepatic artery [CHA]) and no tumor contact with the superior mesenteric vein (SMV) or portal vein (PV) or ≤180° contact without vein contour irregularity. *Not Applicable refers to another clinically significant abnormality that interfered with resectability determination of the target tumor lesion.	an average of 16 weeks
Quality of Life (QoL) Assessed by Karnofsky Performance Status (KPS)	Quality of life will be assessed by the The Karnofsky Performance Status (KPS) Index. KPS scores over time will be compared to those at baseline and changes from baseline will be presented. KPS scores are on a scale (0, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100) of 0 (dead) to 100 (Normal no complaints; no evidence of disease).	Screening, Visit 4 (post gemcitabine induction), Visit 9 (5 weeks), Visit 13 (9 weeks)
Quality of Life Using the Functional Assessment of Cancer Therapy-General (FACT-G) Questionnaire	The FACT-G is a 27-item compilation of general questions divided into 4 primary QoL domains: physical well-being, social/family well-being, emotional well-being and functional well-being. The total FACT-G scores will be summarized by descriptive statistics (e.g., n, mean, median, standard deviation and range). The individual FACT-G score will be presented by frequency and percentage. Scores range from 0-108. High total scores represent better general QoL.	Screening, Visit 4 (post gemcitabine induction), Visit 9 (5 weeks), Visit 13 (9 weeks), every 6 months after Visit 13
Serological Tumor Marker: CA 19-9	Serum was collected for quantitative measurement of CA 19-9.	24 months
Extent of Exposure - Gemcitabine Total Exposure (g)	Measured by the average and median number of exposure of the patients to BC-819 and gemcitabine.	24 months
Extent of Exposure - Gemcitabine Total Number of Treatments	Measured by the average and median number of treatments of the patients to BC-819 and gemcitabine.	24 months
Extent of Exposure - BC-819 Total Exposure (mg)	Measured by the average and median exposure of the patients to BC-819 and gemcitabine.	24 months
Extent of Exposure - BC-819 Total Number of Treatments	Measured by the average and median number of treatments of the patients to BC-819 and gemcitabine.	24 months

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:

Platelet count ≥ 100,000/mm3
Absolute neutrophil count (ANC) ≥ 1500/mm3
Hemoglobin ≥ 10.0 g/dL (may be achieved by transfusion)
Creatinine (≤ 1.5 x ULN)
ALT, AST (≤ 1.5 x ULN)
Total Bilirubin (≤ 1.5 x ULN) 8. Have a target tumor lesion in the pancreas ≤ 6 cm in diameter that is accessible for intratumoral administration by EUS guidance as determined by the physician performing the EUS injection 9. Have a biopsy specimen that is positive for H19 expression (grade 2 or greater staining determined by a pathologist). H19 expression can be determined based on a biopsy specimen collected before study participation, if available. 10. No prior diagnosis of malignancy within 3 years except for curatively treated non-melanoma skin or in situ malignancies 11. Able to comply with the protocol procedures 12. Able and willing to provide written (signed) Informed Consent to participate in the study

Collaborators and Investigators

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

Publications

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