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

NCT01413087 | Terminated Phase 2 Results

• 1 other identifier: BC-PAN-02
• Study Type: interventional
• Target: 12
• Locations: 2 countries
• Sites: 9

Brief Summary

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

Conditions

Pancreas, Adenocarcinoma

Keywords

Pancreatic cancer; Gemcitabine; BC-819; Adenocarcinoma; Resectable; H19 gene; DTA-H19; BioCancell; inodiftagene vixteplasmid

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• Overall Survival (OS)

  24 months

• Response Rate of Target Lesion

  8 weeks

• Resectability of the Target Tumor Lesion

  an average of 16 weeks

• Quality of Life (QoL) Assessed by Karnofsky Performance Status (KPS)

  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

  Screening, Visit 4 (post gemcitabine induction), Visit 9 (5 weeks), Visit 13 (9 weeks), every 6 months after Visit 13

Study Arms (2)

8 mg BC-819 and Gemcitabine

EXPERIMENTAL

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

Biological: Biological/Vaccine: BC-819

12 mg BC-819 and Gemcitabine

EXPERIMENTAL

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

Biological: Biological/Vaccine: BC-819

Interventions

Biological/Vaccine: BC-819 BIOLOGICAL

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 this case, they will be randomized immediately provided there is no evidence of disease progression. After randomization patients will receive 6 weekly IV infusions of gemcitabine at a dose of 1000mg/m2 + 7 intratumoral injections of BC-819 (8 mg or 12 mg according to allocations by randomization)

Also known as: DTA-H19, inodiftagene vixteplasmid

12 mg BC-819 and Gemcitabine; 8 mg BC-819 and Gemcitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females \> 18 years of age
• If female, must not be pregnant or nursing; women of child-bearing potential must practice a medically approved method of contraception
• If male, must practice a medically approved method of contraception if have a partner of childbearing potential
• Histologically or cytologically confirmed adenocarcinoma of the exocrine pancreas
• Locally advanced pancreatic cancer (LAPC) that is clinically unresectable as defined in the NCCN Guidelines
• Karnofsky performance status (KPS) ≥ 70% at baseline
• Adequate hematological, renal, and hepatic function
• 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)
• 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
• 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.

You may not qualify if:

• Have distant metastatic spread (such as liver or lung metastases), peritoneal spread or malignant ascites. Regional lymph node involvement may be considered in accordance with the PI's judgment
• Received any prior therapy for the treatment of pancreatic malignancy (including chemotherapy, immunotherapy, vaccines, monoclonal antibodies, major surgery, or irradiation, whether conventional or investigational, other than up to4 single doses of gemcitabine chemotherapy.Patients who received prior gemcitabine will only be eligible, if they enter the study without evidence of disease progression.
• Known human immunodeficiency virus (HIV) or hepatitis C virus (HCV) or hepatitis B virus (HBV) infection
• Have clinically significant pancreatitis within 12 weeks of treatment
• Have a clinical history of significant coagulopathy
• Have a medical condition contraindicated for endoscopic-guided delivery and/or for IV administration of Gemcitabine 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 participated in any experimental therapeutic research study with an unapproved drug within 4 weeks of the screening visit
• Patients who require ongoing anticoagulation for pre-existing conditions, e.g., thrombophlebitis, pulmonary embolus or atrial fibrillation

Sponsors & Collaborators

• Anchiano Therapeutics Israel Ltd.: lead

Study Sites (9)

Winthrop University Hospital

Mineola, New York, 11501, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Joe Arrington Cancer Research & Treatment Center

Lubbock, Texas, 79410, United States

Location

Carmel Medical Center

Haifa, Israel

Location

Rambam Medical Center

Haifa, Israel

Location

Hadassah Medical Organization

Jerusalem, Israel

Location

Meir Medical Center

Kfar Saba, Israel

Location

Galil Maaravi

Nahariya, Israel

Location

Tel Aviv Medical Center

Tel Aviv, Israel

Location

MeSH Terms

Conditions

Adenocarcinoma; Pancreatic Neoplasms

Interventions

Biological Products

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Complex Mixtures

Results Point of Contact

• Title: Dr. David Kerstein
• Organization: Anchiano Therapeutics Israel Ltd.

david.kerstein@anchiano.com

857-259-4626

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2011
• First Posted: August 10, 2011
• Study Start: September 1, 2011
• Primary Completion: January 1, 2013
• Study Completion: May 1, 2014
• Last Updated: November 1, 2019
• Results First Posted: November 1, 2019

Record last verified: 2019-10

Locations

US (3); IL (6)