Pancreas, AdenocarcinomaPhase 2LAPC-BC-819NCT01413087
Efficacy and Safety of BC-819 and Gemcitabine in Patients With Locally Advanced Pancreatic Adenocarcinoma
A Phase 2 study testing Biological/Vaccine: BC-819 in people with Pancreas, Adenocarcinoma, run by Anchiano Therapeutics Israel Ltd. at 9 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreas, Adenocarcinoma
- What is being tested?
- Biological/Vaccine: BC-819
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 9 sitesin 2 countries
- Study dates
- Sep 2011to May 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 18Show fewer
- 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.
- No prior diagnosis of malignancy within 3 years except for curatively treated non-melanoma skin or in situ malignancies
- Able to comply with the protocol procedures
- Able and willing to provide written (signed) Informed Consent to participate in the study
Who cannot join
- 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
Trial locations and contacts
9 sites in 2 countries.
9 sites in 2 countries
Israel6 sites
Carmel Medical Center
Haifa
Rambam Medical Center
Haifa
Hadassah Medical Organization
Jerusalem
Meir Medical Center
Kfar Saba
Galil Maaravi
Nahariya
Tel Aviv Medical Center
Tel Aviv
United States3 sites
Joe Arrington Cancer Research & Treatment Center
Lubbock, Texas, 79410
Winthrop University Hospital
Mineola, New York, 11501
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
About this study
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
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.
Read more
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
Read the 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.
- Conditions
- Pancreas, Adenocarcinoma
- Being tested
- Biological/Vaccine: BC-819
- Keywords
- Pancreatic cancer, Gemcitabine, BC-819, Adenocarcinoma, Resectable, H19 gene, DTA-H19, BioCancell, inodiftagene vixteplasmid
- Medical subject headings
- Adenocarcinoma, Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biological/Vaccine: BC-819Biological
Also called DTA-H19, inodiftagene vixteplasmid
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)
| Study group | Role | What they receive |
|---|---|---|
| 8 mg BC-819 and Gemcitabine | Experimental | gemcitabine dose of 1000mg/m2 + 8 mg of BC-819 Receives: Biological: Biological/Vaccine: BC-819 |
| 12 mg BC-819 and Gemcitabine | Experimental | gemcitabine dose of 1000mg/m2 + 12 mg of BC-819 Receives: Biological: Biological/Vaccine: BC-819 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 24 months
Secondary outcomes (10)
Overall Survival (OS)
OS was calculated from the date of consent until death due to any cause.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2011 (estimated)
- Study startSep 2011
- Primary completionJan 2013
- Study completionMay 2014
Why it stopped: Due to Sponsor's decision, only 12 patients were randomized \& completed study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Pancreas, AdenocarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Anchiano Therapeutics Israel Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01413087
- Sponsor's protocol ID
- BC-PAN-02
- Acronym
- LAPC-BC-819
- Status last verified
- Oct 2019
- First submitted
- 8 Aug 2011
- Last updated
- 1 Nov 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01413087
- Acronym / sponsor ID
- LAPC-BC-819 / BC-PAN-02
- Conditions
- Pancreas, Adenocarcinoma
- Keywords
- Pancreatic cancer, Gemcitabine, BC-819, Adenocarcinoma, Resectable, H19 gene, DTA-H19, BioCancell
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to Sponsor's decision, only 12 patients were randomized \& completed study.
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Anchiano Therapeutics Israel Ltd.Industry (pharma, biotech, devices)
- Study start
- Sep 2011 (actual)
- Primary completion
- Jan 2013 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 10 Aug 2011 (estimated)
- Results
- Posted 1 Nov 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 8 mg BC-819 and Gemcitabine | Experimental | Biological: Biological/Vaccine: BC-819gemcitabine dose of 1000mg/m2 + 8 mg of BC-819 |
| 12 mg BC-819 and Gemcitabine | Experimental | Biological: Biological/Vaccine: BC-819gemcitabine dose of 1000mg/m2 + 12 mg of BC-819 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Biological/Vaccine: BC-819Also: DTA-H19, inodiftagene vixteplasmidPost 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) | Biological | 12 mg BC-819 and Gemcitabine, 8 mg BC-819 and Gemcitabine |
Primary outcome
Progression-free Survival (PFS)
Time frame: 24 months
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.
10 secondary outcomes
Overall Survival (OS)
Time frame: 24 months
Response Rate of Target Lesion
Time frame: 8 weeks
Resectability of the Target Tumor Lesion
Time frame: an average of 16 weeks
Quality of Life (QoL) Assessed by Karnofsky Performance Status (KPS)
Time frame: 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
Time frame: 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
Time frame: 24 months
Extent of Exposure - Gemcitabine Total Exposure (g)
Time frame: 24 months
Extent of Exposure - Gemcitabine Total Number of Treatments
Time frame: 24 months
Extent of Exposure - BC-819 Total Exposure (mg)
Time frame: 24 months
Extent of Exposure - BC-819 Total Number of Treatments
Time frame: 24 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
9 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Biological/Vaccine: BC-819 in people with Pancreas, Adenocarcinoma, run by Anchiano Therapeutics Israel Ltd. at 9 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 1 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Israel, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free Survival (PFS) (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2019.