FOLFIRINOX Plus PF-04136309 in Patients With Borderline Resectable and Locally Advanced Pancreatic Adenocarcinoma

September 15, 2016 updated by: Washington University School of Medicine

Phase IB Study of FOLFIRINOX Plus PF-04136309 in Patients With Borderline Resectable and Locally Advanced Pancreatic Adenocarcinoma

This phase I trial studies the side effects and optimal dose of PF-04136309 when given with combination chemotherapy (FOLFIRINOX; 5-fluorouracil, leucovorin, irinotecan, oxaliplatin) in treating patients with locally advanced or borderline resectable pancreatic cancer. These patients are not candidates for surgical resection which is the most effective treatment for pancreatic cancer. Giving PF-04136309 together with FOLFIRINOX may shrink pancreatic tumors in some patients so that surgery becomes an option

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

PRIMARY OBJECTIVES:

To define the optimal dose and toxicity of PF-04136309 in combination with FOLFIRINOX (fluorouracil, leucovorin calcium, irinotecan hydrochloride, and oxaliplatin) in patients with borderline resectable and locally advanced pancreatic cancer.

SECONDARY OBJECTIVES:

  • To evaluate the safety of PF-04136309 and FOLFIRINOX by grade 3 or 4 toxicity for clinical use.
  • To determine the tumor control rate (TCR) as defined by stable disease (SD), partial response (PR), and complete response (CR): TCR = SD + PR + CR.

EXPLORATORY OBJECTIVES:

  • To determine the prevalence and function of myeloid-derived suppressor cells (MDSC) in the bone marrow, peripheral circulation, and tumor before and after treatment with PF-04136309 and FOLFIRINOX.
  • To determine the prevalence and function of MDSC in the bone marrow, peripheral circulation, and tumor before and after treatment with FOLFIRINOX.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
44

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine

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.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patient must have histologically or cytologically confirmed pancreatic adenocarcinoma which is borderline resectable or locally advanced; tumors considered borderline include the following: (a) no distant metastases; (b) venous involvement of the superior mesenteric vein/portal vein demonstrating tumor abutment with or without impingement and narrowing of the lumen, encasement of the superior mesenteric vein/portal vein but without encasement of the nearby arteries, or short segment venous occlusion resulting from either tumor thrombus or encasement but with suitable vessel proximal and distal to the area of vessel involvement, allowing for safe resection and reconstruction; (c) gastroduodenal artery encasement up to the hepatic artery with either short segment encasement or direct abutment of the hepatic artery, without extension to the celiac axis; (d) tumor abutment of the superior mesenteric artery not to exceed 180 degrees of the circumference of the vessel wall
  • Patient must have radiographically measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 10 mm with computed tomography (CT) scan or magnetic resonance imaging (MRI) or >= 10 mm with calipers by clinical exam
  • Patient myst be >= 18 years of age.
  • Patient must have life expectancy of > 6 months
  • Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status =< 1

  • Patient must have normal bone marrow and organ function as defined below:

    • Absolute neutrophil count >= 1,500/mcl
    • Platelets >= 100,000/mcl
    • Hemoglobin >= 9.0 g/dL
    • Creatinine should be below the upper limit of normal OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal limits
  • Patient not on anticoagulation must have International Normalized Ratio (INR) and activated partial thromboplastin time (PTT) < 1.5 x ULN
  • Patients who have had a stent placed for biliary obstruction can be included in the study
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately
  • Patient must be able to understand and willing to sign an institutional review board (IRB) approved written informed consent document

Exclusion Criteria:

  • Patient must not have evidence of neuroendocrine tumor, duodenal adenocarcinoma, or ampullary adenocarcinoma
  • Patient must not have a history of other malignancy =< 3 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix
  • Patient must not have received any chemotherapy or radiation for pancreatic cancer
  • Patient must not be receiving any other investigational agents
  • Patient must not have brain metastases; such patients must be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
  • Patient must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to PF-04136309, 5FU (fluorouracil), oxaliplatin, or irinotecan
  • Patient must not be on any CYP3A4 inhibitors or inducers as they may have interaction with PF-04136309 and/or irinotecan
  • Patient must not have an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, any clinically active malabsorption syndrome, inflammatory bowel disease, any condition that increases the risk of severe irinotecan gastrointestinal toxicity, or psychiatric illness/social situations that would limit compliance with study requirements
  • Patient must not be pregnant and/or breastfeeding
  • Patient must not be known to be human immunodeficiency virus (HIV)-positive on combination antiretroviral therapy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Group A (FOLFIRINOX chemotherapy)

Patients receive FOLFIRINOX chemotherapy comprising of:

  • oxaliplatin 85 mg/m2 IV on Day 1
  • irinotecan 180 mg/m2 IV on Day 1
  • leucovorin 400 mg/m2 IV on Day 1
  • 5FU 400 mg/m2 bolus and 2400 mg/m2 CIVI over 46 hours beginning on Day 1

Treatment is repeated every 14 days for 6 cycles.
Other: laboratory biomarker analysis
Correlative studies
Drug: Oxaliplatin
Other Names:
  • 1-OHP
  • Dacotin
  • Dacplat
  • Eloxatin
  • L-OHP
Other: flow cytometry
Correlative studies
Drug: Leucovorin
Other Names:
  • CF
  • CFR
  • LV
Drug: Fluorouracil
Other Names:
  • 5-FU
  • 5-fluorouracil
  • 5-Fluracil
Other: pharmacological study
Correlative studies
Other Names:
  • pharmacological studies
Other: immunohistochemistry staining method
Correlative studies
Other Names:
  • immunohistochemistry
Drug: Irinotecan
Other Names:
  • Campto
  • Camptosar
  • U-101440E
  • CPT-11
Experimental: Group B (FOLFIRINOX and PF-04136309)

Patients receive FOLFIRINOX chemotherapy comprising of:

  • oxaliplatin 85 mg/m2 IV on Day 1
  • irinotecan 180 mg/m2 IV on Day 1
  • leucovorin 400 mg/m2 IV on Day 1
  • 5FU 400 mg/m2 bolus and 2400 mg/m2 CIVI over 46 hours beginning on Day 1
  • PF-04136309 500 mg PO BID on days 1-14

Treatment is repeated every 14 days for 6 cycles.
Other: laboratory biomarker analysis
Correlative studies
Drug: Oxaliplatin
Other Names:
  • 1-OHP
  • Dacotin
  • Dacplat
  • Eloxatin
  • L-OHP
Other: flow cytometry
Correlative studies
Drug: Leucovorin
Other Names:
  • CF
  • CFR
  • LV
Drug: Fluorouracil
Other Names:
  • 5-FU
  • 5-fluorouracil
  • 5-Fluracil
Other: pharmacological study
Correlative studies
Other Names:
  • pharmacological studies
Other: immunohistochemistry staining method
Correlative studies
Other Names:
  • immunohistochemistry
Drug: Irinotecan
Other Names:
  • Campto
  • Camptosar
  • U-101440E
  • CPT-11
Drug: PF-04136309
Other Names:
  • PF-4136309

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Optimal dose and dose-limiting toxicity of PF-04136309 in combination with FOLFIRINOX
Time Frame: 28 days
After completion of two cycles. To find the optimal dose, a 3+3 design will be used.
28 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Safety of PF-04136309 and FOLFIRINOX by grade 3 or 4 toxicity for clinical use.
Time Frame: 120 days (30 days after completion of treatment)
120 days (30 days after completion of treatment)
Disease response rate: TCR = SD + PR + CR
Time Frame: 90 days (completion of cycle 6)
90 days (completion of cycle 6)
Prevalence and function of MDSC in the bone marrow and tumor before and after treatment with PF-04136309 plus FOLFIRINOX or with FOLFIRINOX alone
Time Frame: Baseline and end of cycle 2
Baseline and end of cycle 2
Prevalence and function of MDSC in peripheral circulation before and after treatment with PF-04136309 plus FOLFIRINOX or with FOLFIRINOX alone
Time Frame: Baseline, before cycle 2, before cycle 4, and before cycle 6
Baseline, before cycle 2, before cycle 4, and before cycle 6

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Washington University School of Medicine

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Cancer Institute (NCI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Andrea Wang-Gillam, M.D., PhD, Washington University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

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 Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2012

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2013

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 29, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 8, 2011

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 9, 2011

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 19, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 15, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 201201124
  • NCI-2011-01154 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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