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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:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Washington University School of Medicine

Tracking Information
First Submitted Date  ICMJE July 29, 2011
First Posted Date  ICMJE August 9, 2011
Last Update Posted Date September 19, 2016
Study Start Date  ICMJE April 2012
Actual Primary Completion Date October 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 28, 2013)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: August 8, 2011)
Optimal dose and dose-limiting toxicity of PF-04136309 in combination with FOLFIRINOX [ Time Frame: 30 days ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 28, 2013)
  • 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) ]
  • Disease response rate: TCR = SD + PR + CR [ Time Frame: 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 ]
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: August 8, 2011)
  • Safety of PF-04136309 and FOLFIRINOX by grade 3 or 4 toxicity for clinical use. [ Time Frame: 120 days ]
  • Disease response rate: TCR = SD + PR + CR [ Time Frame: 2 days. At baseline and end of treatment ]
  • 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: 2 days. At baseline and after completion 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: 4 days. At baseline and beginning of cycles 2, 4, and 6 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE FOLFIRINOX Plus PF-04136309 in Patients With Borderline Resectable and Locally Advanced Pancreatic Adenocarcinoma
Official Title  ICMJE Phase IB Study of FOLFIRINOX Plus PF-04136309 in Patients With Borderline Resectable and Locally Advanced Pancreatic Adenocarcinoma
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
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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Pancreatic Neoplasms
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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.

    Interventions:
    • Drug: Oxaliplatin
    • Drug: Irinotecan
    • Drug: Leucovorin
    • Drug: Fluorouracil
    • Other: laboratory biomarker analysis
    • Other: flow cytometry
    • Other: immunohistochemistry staining method
    • Other: pharmacological study
  • 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.

    Interventions:
    • 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
Publications * Nywening TM, Wang-Gillam A, Sanford DE, Belt BA, Panni RZ, Cusworth BM, Toriola AT, Nieman RK, Worley LA, Yano M, Fowler KJ, Lockhart AC, Suresh R, Tan BR, Lim KH, Fields RC, Strasberg SM, Hawkins WG, DeNardo DG, Goedegebuure SP, Linehan DC. Targeting tumour-associated macrophages with CCR2 inhibition in combination with FOLFIRINOX in patients with borderline resectable and locally advanced pancreatic cancer: a single-centre, open-label, dose-finding, non-randomised, phase 1b trial. Lancet Oncol. 2016 May;17(5):651-62. doi: 10.1016/S1470-2045(16)00078-4. Epub 2016 Apr 4.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Estimated Enrollment  ICMJE
 (submitted: June 28, 2013)
44
Original Estimated Enrollment  ICMJE
 (submitted: August 8, 2011)
56
Actual Study Completion Date  ICMJE September 2016
Actual Primary Completion Date October 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01413022
Other Study ID Numbers  ICMJE 201201124
NCI-2011-01154 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Washington University School of Medicine
Study Sponsor  ICMJE Washington University School of Medicine
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Andrea Wang-Gillam, M.D., PhD Washington University School of Medicine
PRS Account Washington University School of Medicine
Verification Date September 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP