Clinical trial NCT01726582: Pancreas Cancer: Molecular Profiling as a Guide to Therapy Before and After Surgery ("Personalized Medicine")
Official title: A Prospective Phase II Trial of Molecular Profiling to Guide Neoadjuvant Therapy for Resectable and Borderline Resectable Adenocarcinoma of the Pancreas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pancreatic Adenocarcinoma
Keywords: pancreas
adenocarcinoma
molecular profile
molecular profiling
pancreatic cancer
pancreas cancer
cancer
molecular target
pancreas head
pancreas neck
pancreas uncinate
pancreas body
pancreas tail
Lead sponsor: Medical College of Wisconsin
Sponsor class: OTHER
Collaborators: name: University of Cincinnati
First posted: 2012-11-15
Enrollment: 229
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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

Hypothesis: Resectability rate, overall survival rate and progression-free survival in subjects with adenocarcinoma of the pancreas will be superior for who receive targeted "personalized" therapy.


Eligibility criteria: Inclusion 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 Eastern Cooperative Oncology Group 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 upper limit of normal (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 extra-pancreatic disease
* No evidence of tumor-arterial abutment (celiac, superior mesenteric artery or hepatic artery)
* If tumor induced narrowing of the superior mesenteric vein, portal vein or superior mesenteric-portal vein confluence is present it must be \<50% of the diameter of the vessel
* Ca19-9 \<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 superior mesenteric artery or celiac axis
* Tumor abutment or encasement (\>180 degrees) of a short segment of the hepatic artery
* Tumor induced narrowing of superior mesenteric vein, portal vein or superior mesenteric-portal vein of \>50% of the diameter of the vessel.
* Short segment occlusion of the superior mesenteric vein, portal vein or superior mesenteric-portal vein confluence with a suitable portal vein above and superior mesenteric vein below, for reconstruction
* CT or MRI findings suspicious for, but not diagnostic of, metastatic disease (based on multidisciplinary assessment at the Medical College of Wisconsin weekly pancreatic cancer conference)
* Biopsy proven N1 disease (regional lymph nodes involved) from pre-referral biopsy or endoscopic ultrasound-guided fine needle aspirate
* Resectable tumor and cancer antigen 19-9 (CA19-9) \>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 human immunodeficiency virus, hepatitis B virus, or hepatitis C virus 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

Primary outcomes:
measure: Number of Subjects Completing Therapy Including Surgical Resection.
timeFrame: At time of surgery (approximately 10 to 20 weeks after screening)
Secondary outcomes:
measure: Overall Survival in Months
timeFrame: 5 years
measure: Progression-free Survival
timeFrame: 5 years
measure: Use of Biomarkers to Determine Course of Treatment
timeFrame: Initiation of therapy (approximately 4 to 12 weeks after screening) until surgery (approximately 10 to 20 weeks after screening)
measure: Histologic Response to Targeted Chemotherapeutic Regimens in Resected Tumors.
timeFrame: At time of surgery (approximately 10 to 20 weeks after screening)
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: University of Cincinnati Cancer Center
state: Ohio
city: Milwaukee
country: United States
facility: Froedtert and The Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Medical College of Wisconsin
name: Douglas B. Evans, M.D., FACS
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical College of Wisconsin
name: Kathleen Christians, M.D., FACS
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical College of Wisconsin
name: Susan Tsai, M.D., M.H.S.
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical College of Wisconsin
name: Paul Ritch, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010 Jun;17(6):1471-4. doi: 10.1245/s10434-010-0985-4.
citation: Tsai S, Christians KK, George B, Ritch PS, Dua K, Khan A, Mackinnon AC, Tolat P, Ahmad SA, Hall WA, Erickson BA, Evans DB. A Phase II Clinical Trial of Molecular Profiled Neoadjuvant Therapy for Localized Pancreatic Ductal Adenocarcinoma. Ann Surg. 2018 Oct;268(4):610-619. doi: 10.1097/SLA.0000000000002957.