Pancreas Cancer: Molecular Profiling as a Guide to Therapy Before and After Surgery ("Personalized Medicine")

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Medical College of Wisconsin
Sponsor:
Information provided by (Responsible Party):
Douglas B Evans, MD, Medical College of Wisconsin
ClinicalTrials.gov Identifier:
NCT01726582
First received: December 28, 2011
Last updated: September 25, 2014
Last verified: September 2014
  Purpose

See treatment pathways at http://www.mcw.edu/surgery/patientinfo/Pancreatic-Cancer-Trial.htm :

In this clinical trial, if the doctor knows or suspects that a growth in the pancreas is cancer (adenocarcinoma), then a sample of the growth is tested (the test is called molecular profiling). The results of the test are used by the doctor to recommend therapy (chemotherapy and radiation therapy) that the patient will receive before having surgery to remove the adenocarcinoma. When the patient goes to surgery, the adenocarcinoma that is removed is tested again. The results of that test are used to guide the choice of therapy after surgery.

The chemotherapy drugs and the radiation therapy used in this clinical trial are already approved for treatment of pancreas cancer. This trial is intended to establish which treatment is best for a specific patient, based on test results from that patient's actual adenocarcinoma. In the past, the decision as to which treatment the patient will receive was not based on testing of the actual adenocarcinoma.

Hypothesis: Resectability rate, overall survival rate and progression-free survival will be superior in patients with adenocarcinoma of the pancreas who receive targeted "personalized" therapy, as compared to historical data of patients who received standard therapy.


Condition Intervention Phase
Pancreatic Adenocarcinoma
Drug: Targeted chemotherapy prior to surgery
Drug: standard FOLFIRINOX chemotherapy prior to surgery
Drug: Gemcitabine after surgery
Other: No additional therapy after surgery
Drug: Targeted chemotherapy after surgery
Radiation: Chemoradiotherapy (cXRT)
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Prospective Phase II Trial of Molecular Profiling to Guide Neoadjuvant Therapy for Resectable and Borderline Resectable Adenocarcinoma of the Pancreas

Resource links provided by NLM:


Further study details as provided by Medical College of Wisconsin:

Primary Outcome Measures:
  • Resectability Rate [ Time Frame: At time of surgery ] [ Designated as safety issue: No ]
    The primary objective is to compare the resectability rate (percent of all patients completing therapy to include surgical resection using a neoadjuvant treatment regimen selected by molecular profiling to historical results with neoadjuvant therapy and surgical resection.


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: Assessed up to five years ] [ Designated as safety issue: No ]
    To compare overall survival (OS) rates of resectable and borderline resectable pancreatic cancer patients treated with molecularly targeted neoadjuvant therapy followed by surgical resection to historical controls treated with standard neoadjuvant therapy and surgical resection.

  • Progression-free Survival [ Time Frame: Assessed from first re-stage after surgery up to five years ] [ Designated as safety issue: No ]
    To compare progression-free survival (PFS) rates of patients with resectable and borderline resectable pancreatic cancer treated with molecularly targeted neoadjuvant therapy followed by surgical resection to historical controls treated with standard neoadjuvant therapy and surgical resection.

  • Frequency with which biomarkers can be utilized to determine treatment. [ Time Frame: At time of diagnosis and after surgery ] [ Designated as safety issue: No ]
    To determine the frequency with which molecular profiling of a patient's tumor by IHC identifies a target for an approved, commercially-available chemotherapeutic regimen.

  • To compare the molecular profile of pretreatment biopsies and resected tumors. [ Time Frame: After surgery ] [ Designated as safety issue: No ]
    We will compare the molecular profile obtained at time of diagnosis with the molecular profile obtained from the resected specimen.

  • To determine the the histologic treatment response to targeted chemotherapeutic regimens in resected tumors. [ Time Frame: At time of surgery ] [ Designated as safety issue: No ]
    Excised tumors will be evaluated for extent of histologic response.

  • To determine the prognostic relevance of radiological response among patients undergoing neoadjuvant therapy. [ Time Frame: Ongoing ] [ Designated as safety issue: No ]
  • To determine the ability to generate primary xenografts of pancreatic cancer from resected tumors. [ Time Frame: 20 weeks post-surgery ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: November 2011
Estimated Study Completion Date: May 2016
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Pre surgery targeted chemo

Depending on the tumor biopsy, treatment prior to surgery will follow arm A or B or C1 or C2.

Arm A:

Targeted chemotherapy prior to surgery: 8 weeks targeted chemotherapy; restaging:

see link to protocol Figures A & C at:

http://www.mcw.edu/surgery/patientinfo/Pancreatic-Cancer-Trial.htm

Drug: Targeted chemotherapy prior to surgery
The molecular profile from the biopsy before surgery will point to a particular chemotherapy treatment.
Other Names:
  • FOLFIRINOX
  • FOLFIRI
  • Gemcitabine with irinotecan
  • Gemcitabine / oxaliplatin
  • Gemcitabine / cisplatinum
  • Gemcitabine / capecitabine
  • Gemcitabine / nab-paclitaxel
  • Capecitabine / nab-paclitaxel
Pre surgery cXRT

Depending on the tumor biopsy, treatment prior to surgery will follow arm A or B or C1 or C2.

Arm B:

Before surgery: Chemoradiotherapy (cRXT); restaging:

see link to protocol Figure C and Figure A or B at:

http://www.mcw.edu/surgery/patientinfo/Pancreatic-Cancer-Trial.htm

Radiation: Chemoradiotherapy (cXRT)
A radio-sensitizing chemotherapy agent (either Gemcitabine or Capecitabine) will be given. Using 3D conformal or IMRT techniques, patients will receive a total dose of 50.4 Gy prescribed to the 95% isodose at 1.8 Gy/fraction (28 fractions).
Other Names:
  • Gemcitabine
  • Capecitabine
Pre surgery targeted chemo, then cXRT

Depending on the tumor biopsy, treatment prior to surgery will follow arm A or B or C1 or C2.

Arm C1:

Before surgery: 8 weeks targeted chemotherapy; restaging; chemoradiotherapy (cXRT); restaging

see link to protocol Figures B and C at:

http://www.mcw.edu/surgery/patientinfo/Pancreatic-Cancer-Trial.htm

Drug: Targeted chemotherapy prior to surgery
The molecular profile from the biopsy before surgery will point to a particular chemotherapy treatment.
Other Names:
  • FOLFIRINOX
  • FOLFIRI
  • Gemcitabine with irinotecan
  • Gemcitabine / oxaliplatin
  • Gemcitabine / cisplatinum
  • Gemcitabine / capecitabine
  • Gemcitabine / nab-paclitaxel
  • Capecitabine / nab-paclitaxel
Radiation: Chemoradiotherapy (cXRT)
A radio-sensitizing chemotherapy agent (either Gemcitabine or Capecitabine) will be given. Using 3D conformal or IMRT techniques, patients will receive a total dose of 50.4 Gy prescribed to the 95% isodose at 1.8 Gy/fraction (28 fractions).
Other Names:
  • Gemcitabine
  • Capecitabine
Pre surgery FOLFIRINOX, then cXRT

Depending on the tumor biopsy, treatment prior to surgery will follow arm A or B or C1 or C2.

Arm C2:

standard FOLFIRINOX chemotherapy prior to surgery: 8 weeks FOLFIRINOX (standard chemotherapy); restaging; standard chemoradiotherapy (cXRT); restaging:

see link at protocol Figures B and C at:

http://www.mcw.edu/surgery/patientinfo/Pancreatic-Cancer-Trial.htm

Drug: standard FOLFIRINOX chemotherapy prior to surgery
A biopsy of the borderline tumor does not provide a molecular profile that can be used to target treatment. The treatmetn will be standard FOLFIRINOX chemotherapy regimen.
Other Names:
  • FOLFIRINOX
  • oxaliplatin
  • irinotecan
  • leucovorin
  • 5 fluoruoracil
Radiation: Chemoradiotherapy (cXRT)
A radio-sensitizing chemotherapy agent (either Gemcitabine or Capecitabine) will be given. Using 3D conformal or IMRT techniques, patients will receive a total dose of 50.4 Gy prescribed to the 95% isodose at 1.8 Gy/fraction (28 fractions).
Other Names:
  • Gemcitabine
  • Capecitabine
After surgery targeted chemo, then cXRT

Depending on the tumor removed during surgery, treatment after surgery will follow arm D1 or D2 or E or F1 or F2 or G.

Arm D1:

After surgery: 8 weeks targeted chemotherapy; restaging; chemoradiotherapy (cXRT); restaging:

see link to protocol Figures A and D at:

http://www.mcw.edu/surgery/patientinfo/Pancreatic-Cancer-Trial.htm

Drug: Targeted chemotherapy after surgery
The molecular profile from the surgical specimen will point to a particular chemotherapy treatment.
Other Names:
  • FOLFIRINOX
  • FOLFIRI
  • Gemcitabine with irinotecan
  • Gemcitabine / oxaliplatin
  • Gemcitabine / cisplatinum
  • Gemcitabine / capecitabine
  • Gemcitabine / nab-paclitaxel
  • Capecitabine / nab-paclitaxel
  • Gemcitabine
  • Capecitabine
  • 5FU
Radiation: Chemoradiotherapy (cXRT)
A radio-sensitizing chemotherapy agent (either Gemcitabine or Capecitabine) will be given. Using 3D conformal or IMRT techniques, patients will receive a total dose of 50.4 Gy prescribed to the 95% isodose at 1.8 Gy/fraction (28 fractions).
Other Names:
  • Gemcitabine
  • Capecitabine
After surgery Gemcitabine, then cXRT

Depending on the tumor removed during surgery, treatment after surgery will follow arm D1 or D2 or E or F1 or F2 or G.

Arm D2:

Gemcitabine after surgery: 8 weeks standard Gemcitabine (chemotherapy); restaging; chemoradiotherapy (cXRT); restaging:

see link to protocol Figures A and D at:

http://www.mcw.edu/surgery/patientinfo/Pancreatic-Cancer-Trial.htm

Drug: Gemcitabine after surgery
Chemotherapy treatment with Gemcitabine.
Other Name: Gemzar
Radiation: Chemoradiotherapy (cXRT)
A radio-sensitizing chemotherapy agent (either Gemcitabine or Capecitabine) will be given. Using 3D conformal or IMRT techniques, patients will receive a total dose of 50.4 Gy prescribed to the 95% isodose at 1.8 Gy/fraction (28 fractions).
Other Names:
  • Gemcitabine
  • Capecitabine
After surgery cXRT

Depending on the tumor removed during surgery, treatment after surgery will follow arm D1 or D2 or E or F1 or F2 or G.

Arm E:

After surgery: chemoradiotherapy (cXRT); restaging:

see lint to protocol Figures A and D at:

http://www.mcw.edu/surgery/patientinfo/Pancreatic-Cancer-Trial.htm

Radiation: Chemoradiotherapy (cXRT)
A radio-sensitizing chemotherapy agent (either Gemcitabine or Capecitabine) will be given. Using 3D conformal or IMRT techniques, patients will receive a total dose of 50.4 Gy prescribed to the 95% isodose at 1.8 Gy/fraction (28 fractions).
Other Names:
  • Gemcitabine
  • Capecitabine
After surgery targeted chemo

Depending on the tumor removed during surgery, treatment after surgery will follow arm D1 or D2 or E or F1 or F2 or G.

Arm F1:

Targeted chemotherapy after surgery: 8 weeks targeted chemotherapy; restaging; 8 weeks targeted chemotherapy; restaging:

see link to protocol Figure E and Figure A or B at:

http://www.mcw.edu/surgery/patientinfo/Pancreatic-Cancer-Trial.htm

Drug: Targeted chemotherapy after surgery
The molecular profile from the surgical specimen will point to a particular chemotherapy treatment.
Other Names:
  • FOLFIRINOX
  • FOLFIRI
  • Gemcitabine with irinotecan
  • Gemcitabine / oxaliplatin
  • Gemcitabine / cisplatinum
  • Gemcitabine / capecitabine
  • Gemcitabine / nab-paclitaxel
  • Capecitabine / nab-paclitaxel
  • Gemcitabine
  • Capecitabine
  • 5FU
After surgery Gemcitabine

Depending on the tumor removed during surgery, treatment after surgery will follow arm D1 or D2 or E or F1 or F2 or G.

Arm F2:

Gemcitabine after surgery : 8 weeks Gemcitabine (chemotherapy); restaging; 8 weeks Gemcitabine (chemotherapy); restaging:

see link to protocol Figure E and Figure A or B at:

http://www.mcw.edu/surgery/patientinfo/Pancreatic-Cancer-Trial.htm

Drug: Gemcitabine after surgery
Chemotherapy treatment with Gemcitabine.
Other Name: Gemzar
After surgery no additional treatment

Depending on the tumor removed during surgery, treatment after surgery will follow arm D1 or D2 or E or F1 or F2 or G.

Arm G:

No additional therapy after surgery:

see link to protocol Figure E and Figure A or B at:

http://www.mcw.edu/surgery/patientinfo/Pancreatic-Cancer-Trial.htm

Other: No additional therapy after surgery
The molecular profile of the tumor that was removed during surgery points to a lack of treatment affect for available therapies. No additional therapy is recommended.
Other Name: Restaged after surgery. No additional therapy.

  Eligibility

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

Enrollment/ eligibility criteria:

  • 18 years of age or older
  • Able to understand and provide written informed consent
  • Diagnosis of adenocarcinoma of the pancreas or high suspicion of adenocarcinoma of the pancreas based on CT and MRI findings as detailed below by "Definition of...."

Treatment Eligibility Criteria:

  • Have an ECOG performance status less than or equal to 2
  • Have biopsy-proven resectable or borderline resectable adenocarcinoma of the pancreas
  • Have adequate organ and bone marrow function as defined by:

    • total leukocytes greater than or equal to 3 x1000/μL
    • absolute neutrophil count (ANC) > or equal to 1.5x 1000/μL
    • hemoglobin > or equal to 9 g/dL
    • platelets > or equal to 100 x 1000/μL
    • creatinine clearance >60 mL/min or creatinine < or equal to 1.5 mg/dL
    • bilirubin < or equal to 2 mg/dL or >2 and declining as described in the protocol
    • aspartate transaminases (AST/SGOT) < or equal to3 x ULN
    • alanine transaminases (ALT/SGPT) < or equal to 3 x ULN
  • Female patients must be post menopausal for > 1 year, surgically sterile, or have a negative pregnancy test and used at least one form of contraception for 4 weeks prior to Day 1 of the study, during study treatment and during the first 4 months after study treatment is discontinued. Male patients must be surgically sterile or use barrier contraception during the study and for 4 months after the last dose of any study drug.

Definition of Resectable Pancreatic Cancer includes:

  • No evidence of extrapancreatic disease
  • No evidence of tumor-arterial abutment (celiac, SMA or HA)
  • If tumor induced narrowing of the SMV, PV or SMPV confluence is present it must be <50% of the diameter of the vessel
  • Ca 19-9 <5000, when bilirubin is <2 (or >2 and declining as described in the protocol)

Definition of Borderline Resectable Pancreatic Cancer to include at least one of the following:

  • Tumor abutment < or equal to 180 degrees of the SMA or celiac axis
  • Tumor abutment or encasement (>180 degrees) of a short segment of the HA
  • Tumor induced narrowing of SMV, PV or SMPV of >50% of the diameter of the vessel.
  • Short segment occlusion of the SMV, PV or SMV-PV with a suitable PV above and SMV below, for reconstruction
  • CT or MRI findings suspicious for, but not diagnostic of, metastatic disease (based on multidisciplinary assessment at the MCW weekly pancreatic cancer conference)
  • Biopsy proven N1 disease (regional lymph nodes involved) from pre-referral biopsy or EUS-guided FNA
  • Resectable tumor and CA 19-9 >5000

Exclusion Criteria:

Any patient with one or more of the following will be excluded:

  • Have received chemotherapy or chemoradiation within 5 years prior of study enrollment
  • Have any previous history of another malignancy (other than cured basal or squamous cell carcinoma of the skin or cured in-situ carcinoma of the cervix) within 5 years of study enrollment
  • Uncontrolled comorbidities including, but not limited to, ongoing or active serious infection, symptomatic congestive heart failure, unstable angina, unstable cardiac arrhythmias, psychiatric illness, excessive obesity, or situations that would limit compliance with the study requirements or the ability to willingly give written informed consent
  • Known HIV, HBV, or HCV infection
  • Pregnant or breast-feeding patients or any patient with child-bearing potential not using contraception 4 weeks prior to, during and 4 months after study treatment is discontinued
  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: NCT01726582

Contacts
Contact: Ann Dwyer, BSN 414-805-8943 adwyer@mcw.edu
Contact: Elizabeth Sheahan-Meyer, BSN 414-805-8921 esmeyer@mcw.edu

Locations
United States, Wisconsin
Froedtert and The Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Ann Dwyer, BSN Dwyer, BSN, RN    414-805-8943    adwyer@mcw.edu   
Contact: Elizabeth Sheahan-Meyer, BSN, RN, OCN    414-805-8921    esmeyer@mcw.edu   
Principal Investigator: Douglas B Evans, M.D., FACS         
Principal Investigator: Kathleen Christians, M.D., FACS         
Principal Investigator: Susan Tsai, M.D., M.H.S.         
Principal Investigator: Paul Ritch, M.D.         
Sponsors and Collaborators
Medical College of Wisconsin
Investigators
Principal Investigator: Douglas B. Evans, M.D., FACS Medical College of Wisconsin
Principal Investigator: Kathleen Christians, M.D., FACS Medical College of Wisconsin
Principal Investigator: Susan Tsai, M.D., M.H.S. Medical College of Wisconsin
Principal Investigator: Paul Ritch, M.D. Medical College of Wisconsin
  More Information

Additional Information:
Publications:
Von Hoff DD, Ramanathan R, Borad M, Laheru D, Smith L, Wood T, et al. SPARC correlation with response to gemcitabine (G) plus nab-paclitaxel (nab-P) in patients with advanced metastatic pancreatic cancer: A phase I/II study. J Clin Oncol 2009; 27(15 Suppl):Abstract 4525
Conroy T, Desseigne F, Ychou M, et al. FNCLCC-FFCD PRODIGE Group. Randomized phase III trial comparing FOLFIRINOX (F: 5FU/leucovorin [LV], irinotecan [I], and oxaliplatin [O]) versus gemcitabine (G) as first-line treatment for metastatic pancreatic adenocarcinoma (MPA): Preplanned interim analysis results of the PRODIGE 4/ACCORD 11 trial. J Clin Oncol 28:15s, 2010 (suppl; abstr 4010).
Keim R, Rao A, Von Hoff D, Evans DB, Christians KK. Molecular Profiling of Endoscopic Ultrasound (EUS) - Guided Fine Needle Aspiration (FNA) specimens in pancreas cancer: A feasibility study. Pancreas Club, Chicago, Ill; May 6-7, 2011

Responsible Party: Douglas B Evans, MD, Chairman, Department of Surgery, Medical College of Wisconsin
ClinicalTrials.gov Identifier: NCT01726582     History of Changes
Other Study ID Numbers: MCW 15565, Advancing a Healthier WI
Study First Received: December 28, 2011
Last Updated: September 25, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Medical College of Wisconsin:
pancreas
adenocarcinoma
molecular profile
molecular profiling
pancreatic cancer
pancreas cancer
cancer
molecular target
pancreas head
pancreas neck
pancreas uncinate
pancreas body
pancreas tail

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Paclitaxel
Irinotecan
Gemcitabine
Capecitabine
Oxaliplatin
Cisplatin
Pancreatin
Pancrelipase
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on October 19, 2014