Pancreas Cancer: Molecular Profiling as a Guide to Therapy Before and After Surgery ("Personalized Medicine")
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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 |
- 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.
- 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: | August 2014 |
| Estimated Primary Completion Date: | March 2014 (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:
|
|
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:
|
|
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:
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:
|
|
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:
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:
|
|
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:
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:
|
|
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:
|
|
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:
|
|
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:
|
|
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 |
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| Contact: Ann Dwyer, BSN | 414-805-8943 | adwyer@mcw.edu |
| Contact: Elizabeth Sheahan-Meyer, BSN | 414-805-8921 | esmeyer@mcw.edu |
| 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. | |
| 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:
| 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: | November 9, 2012 |
| 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 Adenocarcinoma, Mucinous Pancreatic Neoplasms Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Neoplasms, Cystic, Mucinous, and Serous Digestive System Neoplasms Neoplasms by Site Endocrine Gland Neoplasms Digestive System Diseases Pancreatic Diseases Endocrine System Diseases Gemcitabine |
Oxaliplatin Irinotecan Capecitabine Cisplatin Paclitaxel Pancreatin Pancrelipase Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Radiation-Sensitizing Agents Physiological Effects of Drugs Gastrointestinal Agents Antimetabolites, Antineoplastic Antimetabolites |
ClinicalTrials.gov processed this record on May 16, 2013