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

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ClinicalTrials.gov Identifier: NCT01413022
Recruitment Status : Completed
First Posted : August 9, 2011
Last Update Posted : September 19, 2016
Sponsor:
Collaborator:
Information provided by (Responsible Party):

Study Description
Brief Summary:
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 or disease Intervention/treatment 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

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 Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 44 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : April 2012
Primary Completion Date : October 2013
Study Completion Date : September 2016

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
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


Outcome Measures

Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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) ]
  2. Disease response rate: TCR = SD + PR + CR [ Time Frame: 90 days (completion of cycle 6) ]
  3. 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 ]
  4. 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 ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01413022


Locations
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
National Cancer Institute (NCI)
Investigators
Principal Investigator: Andrea Wang-Gillam, M.D., PhD Washington University School of Medicine
More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT01413022     History of Changes
Other Study ID Numbers: 201201124
NCI-2011-01154 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
First Posted: August 9, 2011    Key Record Dates
Last Update Posted: September 19, 2016
Last Verified: September 2016

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
Antineoplastic Agents, Phytogenic
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs