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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Washington University School of Medicine
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT01413022
First received: July 29, 2011
Last updated: October 14, 2014
Last verified: October 2014
  Purpose

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


Condition Intervention Phase
Pancreatic Neoplasms
Drug: Oxaliplatin
Drug: Irinotecan
Drug: Leucovorin
Drug: Fluorouracil
Other: laboratory biomarker analysis
Other: flow cytometry
Other: immunohistochemistry staining method
Other: pharmacological study
Drug: PF-04136309
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase IB Study of FOLFIRINOX Plus PF-04136309 in Patients With Borderline Resectable and Locally Advanced Pancreatic Adenocarcinoma

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Optimal dose and dose-limiting toxicity of PF-04136309 in combination with FOLFIRINOX [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    After completion of two cycles. To find the optimal dose, a 3+3 design will be used.


Secondary Outcome Measures:
  • 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) ] [ Designated as safety issue: Yes ]
  • Disease response rate: TCR = SD + PR + CR [ Time Frame: 90 days (completion of cycle 6) ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 44
Study Start Date: April 2012
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Drug: Oxaliplatin
Other Names:
  • 1-OHP
  • Dacotin
  • Dacplat
  • Eloxatin
  • L-OHP
Drug: Irinotecan
Other Names:
  • Campto
  • Camptosar
  • CPT-11
  • U-101440E
Drug: Leucovorin
Other Names:
  • CF
  • CFR
  • LV
Drug: Fluorouracil
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
Other: laboratory biomarker analysis
Correlative studies
Other: flow cytometry
Correlative studies
Other: immunohistochemistry staining method
Correlative studies
Other Name: immunohistochemistry
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
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.

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

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.
  Eligibility

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

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
  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: NCT01413022

Locations
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Andrea Wang-Gillam, M.D., Ph.D.    314-362-5740    awang@dom.wustl.edu   
Principal Investigator: Andrea Wang-Gillam, M.D., Ph.D.         
Sub-Investigator: Benjamin Tan, M.D.         
Sub-Investigator: William Hawkins, M.D.         
Sub-Investigator: Steven Strasberg, M.D.         
Sub-Investigator: Joel Picus, M.D.         
Sub-Investigator: A. Craig Lockhart, M.D.         
Sub-Investigator: Steven Sorscher, M.D.         
Sub-Investigator: Rama Suresh, M.D.         
Sub-Investigator: Simon Peter Goedegeburre, Ph.D.         
Sub-Investigator: Dayna Early, M.D.         
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Andrea Wang-Gillam, M.D., PhD Washington University School of Medicine
  More Information

Additional Information:
No publications provided

Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT01413022     History of Changes
Other Study ID Numbers: 201201124, NCI-2011-01154
Study First Received: July 29, 2011
Last Updated: October 14, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Pancreatic Neoplasms
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
Oxaliplatin
Irinotecan
Fluorouracil
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Radiation-Sensitizing Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 19, 2014