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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
BioCancell Ltd.
ClinicalTrials.gov Identifier:
NCT01413087
First received: August 8, 2011
Last updated: August 9, 2012
Last verified: May 2012
  Purpose

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


Condition Intervention Phase
Pancreas, Adenocarcinoma
Biological: Biological/Vaccine: BC-819
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multi-Center, Open-Label, Randomized, Phase 2b Study to Evaluate the Efficacy and Safety of BC-819 and Gemcitabine in Patients With Locally Advanced Pancreatic Adenocarcinoma

Resource links provided by NLM:


Further study details as provided by BioCancell Ltd.:

Primary Outcome Measures:
  • To compare the effect of intratumoral endoscopic ultrasound injection of BC-819 administered with intravenous gemcitabine on progression-free survival. [ Time Frame: an average of 16 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • overall survival (OS) [ Time Frame: an average of 1 year ] [ Designated as safety issue: No ]
  • Response rate [ Time Frame: an average of 12 weeks ] [ Designated as safety issue: No ]
    Response rate will be assessed both for the primary target tumor lesion alone and overall, including development of metastases

  • Resectability of the target tumor lesion [ Time Frame: an average of 16 weeks ] [ Designated as safety issue: No ]
  • Quality of Life [ Time Frame: an average of 1 year ] [ Designated as safety issue: No ]
    QoL will be measured by Karnofsky Performance Status and using the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire

  • Serological Tumor Marker: CA 19-9 [ Time Frame: Every 4-5 weeks, for an average of 16 weeks ] [ Designated as safety issue: No ]
  • Duration of response [ Time Frame: an average of 24 weeks ] [ Designated as safety issue: No ]
  • Safety [ Time Frame: an average of 16 weeks ] [ Designated as safety issue: Yes ]
    Incidence and severity of adverse events and changes in clinical laboratory values

  • Failure-free survival [ Time Frame: an average of 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 70
Study Start Date: September 2011
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BC-819 and Gemcitabine 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 this case, they will be randomized immediately provided there is no evidence of disease progression.

After randomization patients will receive gemcitabine at a dose of 1000mg/m2 + 8 mg doses of BC-819 or gemcitabine at a dose of 1000mg/m2 + 12 mg doses of BC-819

Other Name: DTA-H19

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Males or females > 18 years of age
  2. If female, must not be pregnant or nursing; women of child-bearing potential must practice a medically approved method of contraception
  3. If male, must practice a medically approved method of contraception if have a partner of childbearing potential
  4. Histologically or cytologically confirmed adenocarcinoma of the exocrine pancreas
  5. Locally advanced pancreatic cancer (LAPC) that is clinically unresectable as defined in the NCCN Guidelines
  6. Karnofsky performance status (KPS) ≥ 70% at baseline
  7. 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)
  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

Exclusion Criteria:

  1. 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
  2. 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.
  3. Known human immunodeficiency virus (HIV) or hepatitis C virus (HCV) or hepatitis B virus (HBV) infection
  4. Have clinically significant pancreatitis within 12 weeks of treatment
  5. Have a clinical history of significant coagulopathy
  6. 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
  7. Have participated in any experimental therapeutic research study with an unapproved drug within 4 weeks of the screening visit
  8. Patients who require ongoing anticoagulation for pre-existing conditions, e.g., thrombophlebitis, pulmonary embolus or atrial fibrillation
  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: NCT01413087

Locations
United States, New York
Winthrop University Hospital
Mineola, New York, United States, 11501
United States, Pennsylvania
Thomas Jefferson University
Philadelphia, Pennsylvania, United States
United States, Texas
Joe Arrington Cancer Research & Treatment Center
Lubbock, Texas, United States, 79410
Israel
Carmel Medical Center
Haifa, Israel
Rambam Medical Center
Haifa, Israel
Hadassah Medical Organization
Jerusalem, Israel
Meir Medical Center
Kfar Saba, Israel
Galil Maaravi
Nahariya, Israel
Tel Aviv Medical Center
Tel Aviv, Israel
Sponsors and Collaborators
BioCancell Ltd.
  More Information

No publications provided

Responsible Party: BioCancell Ltd.
ClinicalTrials.gov Identifier: NCT01413087     History of Changes
Other Study ID Numbers: BC-PAN-02
Study First Received: August 8, 2011
Last Updated: August 9, 2012
Health Authority: United States: Food and Drug Administration
Israel: Ministry of Health

Keywords provided by BioCancell Ltd.:
Pancreatic cancer
Gemcitabine
BC-819
Adenocarcinoma
Resectable
H19 gene
DTA-H19
BioCancell

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gemcitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on July 31, 2014