Advanced Pancreatic CancerPhase 1NCT01764477
Safety and Efficacy Study of PRI-724 Plus Gemcitabine in Subjects With Advanced or Metastatic Pancreatic Adenocarcinoma
A Phase 1 study testing PRI-724 in people with Advanced Pancreatic Cancer and Metastatic Pancreatic Cancer, run by Prism Pharma Co., Ltd. at 5 sites in United States.
Trial summary
Laboratory studies suggest that the study drug may stop cancer cells from growing by affecting an interaction between proteins in the cells referred to as cAMP-response element-binding protein and ß-catenin. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Pancreatic Cancer, Metastatic Pancreatic Cancer, Pancreatic Adenocarcinoma
- What is being tested?
- PRI-724
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 5 sitesUnited States
- Study dates
- Apr 2013to Oct 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Male or female patients, > 18 years of age.
- Patients with a documented (histologically- or cytologically-proven) epithelial cell/adenocarcinoma of the pancreas that is relapsed, locally advanced, or metastatic.
- Patients with measurable or evaluable disease according to the response evaluation criteria in solid tumors
- Patients eligible for second-line therapy after failing first-line therapy with the regimen FOLFIRINOX.
- Patients with a malignancy that is currently not amenable to surgical intervention, due to either medical contraindications or non-resectability of the tumor.
- Patients with a Karnofsky Performance Status of 70% to 100% (or equivalent, Eastern Cooperative Oncology Group [ECOG] performance status of 0 or 1); Performance Status Evaluation), and an anticipated life expectancy of ≥ 3 months.
- Patients, both male and female, who are either not of childbearing potential or who agree to use a medically effective method of contraception during the study and for 3 months after the last dose of study drug.
- Patients with the ability to understand and give written informed consent for participation in this trial, including all evaluations and procedures as specified by this protocol.
Who cannot join
- Women who are pregnant or lactating. Women of child-bearing potential (WOCBP) and fertile men with a WOCBP partner, not using adequate birth control.
- Patients with islet cell tumors or other non-epithelial cell malignancies of the pancreas.
- Patients with known CNS (or leptomeningeal) metastases not controlled by prior surgery or radiotherapy, or patients with symptoms suggesting CNS involvement for which treatment is required.
- Patients with an active second malignancy within the last 2 years with the exception of:
- Treated, non-melanoma skin cancers
- Treated CIS of the breast or cervix
Show all 36Show fewer
- Controlled, superficial bladder carcinoma
- T1a or b prostate carcinoma involving < 5% of resected tissue and PSA within normal limits (WNL) since resection
- Patients with any of the following hematologic abnormalities at baseline:
- Hemoglobin < 9.0 g/dL
- Absolute neutrophil count (ANC) < 1,500 per mm3
- Platelet count < 100,000 per mm3
- Patients with any of the following serum chemistry abnormalities at baseline:
- Total bilirubin > 1.5× the ULN for the institution, unless considered due to Gilbert's Syndrome
- AST or ALT > 3× the ULN for the institution (> 5× ULN if due to hepatic involvement by tumor)
- Serum albumin < 2.5 g/dL
- Serum creatinine > 1.5× ULN (or a calculated creatinine clearance < 60 mL/min/1.73 m2)
- Patients with a significant cardiovascular disease or condition, including:
- Congestive heart failure (CHF) currently requiring therapy
- Need for anti-arrhythmic therapy for a ventricular arrhythmias
- Severe conduction disturbances
- Angina pectoris requiring therapy
- Left ventricular ejection fraction (LVEF) < 50% by MUGA or echocardiogram
- QTcF interval > 450 msec (males) or > 470 msec (females)
- Uncontrolled hypertension (per Investigator's discretion)
- Class III or IV cardiovascular disease according to the New York Heart Association's (NYHA) Functional Criteria.
- Myocardial infarction (MI) within 6 months prior to first study drug administration
- Patients with known osteopenia or osteoporosis.
- Patients with a known or suspected hypersensitivity to either gemcitabine or any of the components of PRI-724.
- Patients with a history of human immunodeficiency virus (HIV) or active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).
- Patients with any other serious/active/uncontrolled infection, any infection requiring parenteral antibiotics, or unexplained fever > 38ºC within 2 weeks prior to first study drug administration.
- Patients with inadequate recovery from acute toxicity associated with any prior antineoplastic therapy
- Patients with inadequate recovery from any prior surgical procedure, or patients having undergone any major surgical procedure within 1 month prior to first study drug administration.
- Patients with any other life-threatening illness, significant organ system dysfunction, or clinically significant laboratory abnormality, which, in the opinion of the Investigator, would either compromise the patient's safety or interfere with evaluation of the safety of the study drug
- Patients with a psychiatric disorder or altered mental status that would preclude understanding of the informed consent process and/or completion of the necessary studies
- Patients with the inability, in the opinion of the Investigator, to comply with the protocol requirements
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
USC Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Mayo Clinic
Rochester, Minnesota, 55905
University of California, San Francisco
San Francisco, California, 94115
University of Washington Seattle Cancer Care Alliance
Seattle, Washington, 98109
About this study
Official title: Phase Ib Multicenter, Cohort Dose Escalation Trial to Determine the Safety, Tolerance and Preliminary Antineoplastic Activity of Gemcitabine Administered in Combination With Continuous Intravenous Doses of PRI-724, a CBP/ β- Catenin Inhibitor, to Patients With Advanced or Metastatic Pancreatic Adenocarcinoma Eligible for Second-Line Therapy After Failing First-Line Therapy With FOLFIRINOX (or FOLFOX)
Laboratory studies suggest that the study drug may stop cancer cells from growing by affecting an interaction between proteins in the cells referred to as cAMP-response element-binding protein and ß-catenin.
The purpose of this research study is to determine the highest safe dose of study drug that may be used when it is given together with a chemotherapy drug to patients with cancer of the pancreas.
Read the detailed description
PRI-724 is a small molecule antagonist that binds to the co-activator CBP thereby specifically inhibiting the subset of Wnt/β-catenin-driven genes that are up-regulated in cancer cells. PRI-724 is being developed as a potential antineoplastic agent.
Purpose:
To determine the safety, tolerability, dose-limiting toxicities (DLTs), and maximum tolerated dose (MTD) of sequential escalating doses per cohort of PRI-724 administered in combination with gemcitabine to patients with adenocarcinoma of the pancreas that is locally advanced, metastatic, or otherwise inoperable, who are candidates for second-line therapy after failing first-line therapy with FOLFIRINOX (i.e., folinic acid [leucovorin], fluorouracil, irinotecan, oxaliplatin)
- PRI-724: 320, 640, 905 mg/m2/day, continuous intravenous (CIV) infusion over 24 h, daily × 7 days, 1 week on with 1 week recovery × 2 (4 weeks equals 1 cycle)
- Gemcitabine: 1000 mg/m2 IV over 30 minutes; 3 weeks on with 1 week recovery (4 weeks equals 1 cycle)
Patients with documented, measurable or evaluable adenocarcinoma of the pancreas that is locally advanced, metastatic, or otherwise inoperable, who are candidates for second-line therapy after failing first-line therapy with FOLFIRINOX, will be entered into this phase 1b, multicenter, open-label, non-randomized, dose-escalation per cohort study. The trial is designed to evaluate the safety, tolerability, DLT(s), and MTD of escalating doses of PRI-724, a CBP/ β- catenin inhibitor, when administered in combination with a standard dose of gemcitabine. Correlative studies include characterization of the PK profiles of PRI-724 and gemcitabine, evaluation of the utility of potential PD markers of PRI-724 activity, as well as preliminary assessment of the antineoplastic activity of PRI-724 plus gemcitabine in this patient population.
- Being tested
- PRI-724
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PRI-724Drug
Gemcitabine: 1000 mg/m2 IV over 30 minutes; once weekly dosing; 3 weeks on with 1 week recovery (4 weeks per cycle)
PRI-724:
Cohort 1: 320 mg/m2/day; Cohort 2: 640 mg/m2/day; Cohort 3: 905 mg/m2/day; Continuous IV over 24 hours; daily x 7 days; 1 week on with 1 week recovery × 2 (4 weeks per cycle)
| Study group | Role | What they receive |
|---|---|---|
| PRI-724 and Gemcitabine | Experimental | This study will have one arm: all enrolled subjects will be treated with both PRI-724 and Gemcitabine. Receives: Drug: PRI-724 |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Maximum Tolerated Dose (MTD) of PRI-724 + Gemcitabine measured by the number of dose limiting toxicities (DLTs) that occur.
If no DLT occurs in the first 3 patients of a cohort, the dose will be escalated to the next dose cohort. If 1 DLT occurs in the first 3 patients of a cohort, that cohort is expanded to 6 patients. If more than 1 DLT occurs in a 6 patient cohort, escalation is stopped \& next lower dose is expanded to 12 patients to confirm the MTD.
Measured: 18 months. DLTs will be measured as they occur throughout the patients' time on study.
Secondary outcomes (5)
Pharmacokinetic parameters of C max , T max , AUC (tau), and t ½.
The secondary outcome measures of PKs, PDs, MMP7, hair follicle sampling, and Response Criteria by RECIST comprise the correlative studies of this trial and are designed to evaluate PK profiles, assess and evaluate the utility of potential biomarkers, and evaluate antineoplastic activity of PRI-724 + Gemcitabine.
Measured: C 1 D 1 hrs 0, 1, 2, D 8 hrs 0, :15, :30, 1, 2, 4, 6, D 9 hrs 24, D 15 at hrs 0
Pharmacodynamic mRNA expression of survivin
The secondary outcome measures of PKs, PDs, MMP7, hair follicle sampling, and Response Criteria by RECIST comprise the correlative studies of this trial and are designed to evaluate PK profiles, assess and evaluate the utility of potential biomarkers, and evaluate antineoplastic activity of PRI-724 + Gemcitabine
Measured: C 1 D 1, D 8, D 15, D 22, All Cycles D 22, end of treatment
Evaluation of antineoplastic activity of PRI-724 + gemcitabine per RECIST 1.1 criteria
The secondary outcome measures of PKs, PDs, MMP7, hair follicle sampling, and Response Criteria by RECIST comprise the correlative studies of this trial and are designed to evaluate PK profiles, assess and evaluate the utility of potential biomarkers, and evaluate antineoplastic activity of PRI-724 + Gemcitabine
Measured: Screening, end of C 2, every 2 cycles, end of treatment
MMP7 levels in blood as ng/ml
The secondary outcome measures of PKs, PDs, MMP7, hair follicle sampling, and Response Criteria by RECIST comprise the correlative studies of this trial and are designed to evaluate PK profiles, assess and evaluate the utility of potential biomarkers, and evaluate antineoplastic activity of PRI-724 + Gemcitabine.
Measured: C 1 Wk 1, Wk 4, Wk 4 all cycles, end of treatment
Gene expressions in hair follicle epithelial cells
The secondary outcome measures of PKs, PDs, MMP7, hair follicle sampling, and Response Criteria by RECIST comprise the correlative studies of this trial and are designed to evaluate PK profiles, assess and evaluate the utility of potential biomarkers, and evaluate antineoplastic activity of PRI-724 + Gemcitabine
Measured: Screening, C 1 D 14, C 2 Wk 4, end of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2013 (estimated)
- Study startApr 2013
- Primary completionOct 2015
- Study completionOct 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Pancreatic CancerStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Prism Pharma Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- inVentiv Health Clinical
- Responsible party
- Sponsor
- Investigators
- Robert R. McWilliams, M.D., Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01764477
- Sponsor's protocol ID
- PRI-724-102
- Status last verified
- Oct 2015
- First submitted
- 12 Dec 2012
- Last updated
- 17 Aug 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ib Multicenter, Cohort Dose Escalation Trial to Determine the Safety, Tolerance and Preliminary Antineoplastic Activity of Gemcitabine Administered in Combination With Continuous Intravenous Doses of PRI-724, a CBP/ β- Catenin Inhibitor, to Patients With Advanced or Metastatic Pancreatic Adenocarcinoma Eligible for Second-Line Therapy After Failing First-Line Therapy With FOLFIRINOX (or FOLFOX)
- ClinicalTrials.gov ID
- NCT01764477
- Acronym / sponsor ID
- PRI-724-102
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Prism Pharma Co., Ltd.Industry (pharma, biotech, devices)
- Collaborators
- inVentiv Health Clinical
- Study start
- Apr 2013
- Primary completion
- Oct 2015 (actual)
- Study completion
- Oct 2015 (actual)
- First posted
- 9 Jan 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Laboratory studies suggest that the study drug may stop cancer cells from growing by affecting an interaction between proteins in the cells referred to as cAMP-response element-binding protein and ß-catenin.
The purpose of this research study is to determine the highest safe dose of study drug that may be used when it is given together with a chemotherapy drug to patients with cancer of the pancreas.
Detailed description
PRI-724 is a small molecule antagonist that binds to the co-activator CBP thereby specifically inhibiting the subset of Wnt/β-catenin-driven genes that are up-regulated in cancer cells. PRI-724 is being developed as a potential antineoplastic agent.
Purpose:
To determine the safety, tolerability, dose-limiting toxicities (DLTs), and maximum tolerated dose (MTD) of sequential escalating doses per cohort of PRI-724 administered in combination with gemcitabine to patients with adenocarcinoma of the pancreas that is locally advanced, metastatic, or otherwise inoperable, who are candidates for second-line therapy after failing first-line therapy with FOLFIRINOX (i.e., folinic acid [leucovorin], fluorouracil, irinotecan, oxaliplatin)
- PRI-724: 320, 640, 905 mg/m2/day, continuous intravenous (CIV) infusion over 24 h, daily × 7 days, 1 week on with 1 week recovery × 2 (4 weeks equals 1 cycle)
- Gemcitabine: 1000 mg/m2 IV over 30 minutes; 3 weeks on with 1 week recovery (4 weeks equals 1 cycle)
Patients with documented, measurable or evaluable adenocarcinoma of the pancreas that is locally advanced, metastatic, or otherwise inoperable, who are candidates for second-line therapy after failing first-line therapy with FOLFIRINOX, will be entered into this phase 1b, multicenter, open-label, non-randomized, dose-escalation per cohort study. The trial is designed to evaluate the safety, tolerability, DLT(s), and MTD of escalating doses of PRI-724, a CBP/ β- catenin inhibitor, when administered in combination with a standard dose of gemcitabine. Correlative studies include characterization of the PK profiles of PRI-724 and gemcitabine, evaluation of the utility of potential PD markers of PRI-724 activity, as well as preliminary assessment of the antineoplastic activity of PRI-724 plus gemcitabine in this patient population.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PRI-724 and Gemcitabine | Experimental | Drug: PRI-724This study will have one arm: all enrolled subjects will be treated with both PRI-724 and Gemcitabine. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male or female patients, > 18 years of age.
- Patients with a documented (histologically- or cytologically-proven) epithelial cell/adenocarcinoma of the pancreas that is relapsed, locally advanced, or metastatic.
- Patients with measurable or evaluable disease according to the response evaluation criteria in solid tumors
- Patients eligible for second-line therapy after failing first-line therapy with the regimen FOLFIRINOX.
- Patients with a malignancy that is currently not amenable to surgical intervention, due to either medical contraindications or non-resectability of the tumor.
Key exclusion criteria (36 listed)
- Women who are pregnant or lactating. Women of child-bearing potential (WOCBP) and fertile men with a WOCBP partner, not using adequate birth control.
- Patients with islet cell tumors or other non-epithelial cell malignancies of the pancreas.
- Patients with known CNS (or leptomeningeal) metastases not controlled by prior surgery or radiotherapy, or patients with symptoms suggesting CNS involvement for which treatment is required.
- Patients with an active second malignancy within the last 2 years with the exception of:
- Patients with any of the following hematologic abnormalities at baseline:
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 |
|---|---|---|
| PRI-724Gemcitabine: 1000 mg/m2 IV over 30 minutes; once weekly dosing; 3 weeks on with 1 week recovery (4 weeks per cycle) PRI-724: Cohort 1: 320 mg/m2/day; Cohort 2: 640 mg/m2/day; Cohort 3: 905 mg/m2/day; Continuous IV over 24 hours; daily x 7 days; 1 week on with 1 week recovery × 2 (4 weeks per cycle) | Drug | PRI-724 and Gemcitabine |
Primary outcome
The Maximum Tolerated Dose (MTD) of PRI-724 + Gemcitabine measured by the number of dose limiting toxicities (DLTs) that occur.
Time frame: 18 months. DLTs will be measured as they occur throughout the patients' time on study.
If no DLT occurs in the first 3 patients of a cohort, the dose will be escalated to the next dose cohort. If 1 DLT occurs in the first 3 patients of a cohort, that cohort is expanded to 6 patients. If more than 1 DLT occurs in a 6 patient cohort, escalation is stopped \& next lower dose is expanded to 12 patients to confirm the MTD.
5 secondary outcomes
Pharmacokinetic parameters of C max , T max , AUC (tau), and t ½.
Time frame: C 1 D 1 hrs 0, 1, 2, D 8 hrs 0, :15, :30, 1, 2, 4, 6, D 9 hrs 24, D 15 at hrs 0
Pharmacodynamic mRNA expression of survivin
Time frame: C 1 D 1, D 8, D 15, D 22, All Cycles D 22, end of treatment
Evaluation of antineoplastic activity of PRI-724 + gemcitabine per RECIST 1.1 criteria
Time frame: Screening, end of C 2, every 2 cycles, end of treatment
MMP7 levels in blood as ng/ml
Time frame: C 1 Wk 1, Wk 4, Wk 4 all cycles, end of treatment
Gene expressions in hair follicle epithelial cells
Time frame: Screening, C 1 D 14, C 2 Wk 4, end of treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2017.
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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.
Robert R. McWilliams, M.D. principal investigator
Mayo Clinic
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PRI-724 in people with Advanced Pancreatic Cancer and Metastatic Pancreatic Cancer, run by Prism Pharma Co., Ltd. at 5 sites in United States.
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 8 inclusion and 36 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: finished, as of the sponsor's last update on 17 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
The Maximum Tolerated Dose (MTD) of PRI-724 + Gemcitabine measured by the number of dose limiting toxicities (DLTs) that occur. (time frame: 18 months. DLTs will be measured as they occur throughout the patients' time on study.). 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 17 Aug 2017.