Pancreatic Adenocarcinoma
Conditions
Keywords
pancreas, adenocarcinoma, molecular profile, molecular profiling, pancreatic cancer, pancreas cancer, cancer, molecular target, pancreas head, pancreas neck, pancreas uncinate, pancreas body, pancreas tail
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.
Interventions
DRUGMilestone 1: Targeted chemotherapy prior to surgery
The molecular profile from the biopsy before surgery will point to a particular chemotherapy treatment.
RADIATIONMilestone 2: Chemoradiotherapy (cXRT)
A radio-sensitizing chemotherapy agent (either Gemcitabine or Capecitabine) will be given. Using 3D conformal or intensity-modulated radiation therapy (IMRT) techniques, patients will receive a total dose of 50.4 Gy prescribed to the 95% isodose at 1.8 Gy/fraction (28 fractions).
DRUGMilestone 3: Targeted chemotherapy prior to surgery
The molecular profile from the biopsy before surgery will point to a particular chemotherapy treatment.
RADIATIONMilestone 3: 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).
DRUGMilestone 4: 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 treatment will be standard FOLFIRINOX chemotherapy regimen.
RADIATIONMilestone 4: 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).
DRUGMilestone 5: Targeted chemotherapy after surgery
The molecular profile from the surgical specimen will point to a particular chemotherapy treatment.
RADIATIONMilestone 5: 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).
DRUGMilestone 6: Gemcitabine after surgery
Chemotherapy treatment with Gemcitabine.
RADIATIONMilestone 6: 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).
RADIATIONMilestone 7: 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).
DRUGMilestone 8: Targeted chemotherapy after surgery
The molecular profile from the surgical specimen will point to a particular chemotherapy treatment.
DRUGMilestone 9: Gemcitabine after surgery
Chemotherapy treatment with Gemcitabine.
OTHERMilestone 10: 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.
Sponsors
University of Cincinnati
Medical College of Wisconsin
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Completing Therapy Including Surgical Resection. | At time of surgery (approximately 10 to 20 weeks after screening) | This outcome measure is the number of subjects completing therapy up to and including surgical resection. In this context, surgical excision of residual tumor is an option in the progression of usual care. Surgery was contraindicated for some participants. This measure is the number of subject who were eligible for and completed the surgical procedure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival in Months | 5 years | This measure is the median time of survival (in months) at five years from the initiation of therapy. Results will be presented for two cohorts: subjects completing neoadjuvant therapy and surgical resection; and subjects completing neoadjuvant therapy but without surgical resection. |
| Progression-free Survival | 5 years | This measure is the number of subjects not experiencing tumor progression at five years from initiating therapy. |
| Use of Biomarkers to Determine Course of Treatment | Initiation of therapy (approximately 4 to 12 weeks after screening) until surgery (approximately 10 to 20 weeks after screening) | The number of subjects for whom a biomarker (i.e., molecular profile) was used to determine the course of treatment. |
| Histologic Response to Targeted Chemotherapeutic Regimens in Resected Tumors. | At time of surgery (approximately 10 to 20 weeks after screening) | The number of tumors showing a histologic response. Histological response will be measured using the Ryan Score method as defined by the American Joint Committee on Cancer, 7th edition (see Edge, 2010). Grading categories are defined as: Grade 0 (complete response); Grade 1 (near complete response); Grade 2 (partial response); and Grade 3 (poor or no response). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Milestones Related to Therapy Milestone 1: Targeted chemotherapy prior to surgery: 8 weeks targeted chemotherapy; restaging.
Milestone 2: Before surgery: Chemoradiotherapy (cRXT); restaging Milestone 3: Before surgery: 8 weeks targeted chemotherapy; restaging; chemoradiotherapy (cXRT); restaging.
Milestone 4: standard FOLFIRINOX chemotherapy prior to surgery: 8 weeks FOLFIRINOX (standard chemotherapy); restaging; standard chemoradiotherapy (cXRT); restaging.
Milestone 5: After surgery: 8 weeks targeted chemotherapy; restaging; chemoradiotherapy (cXRT); restaging.
Milestone 6: Gemcitabine after surgery: 8 weeks standard Gemcitabine (chemotherapy); restaging; chemoradiotherapy (cXRT); restaging.
Milestone 7: After surgery: chemoradiotherapy (cXRT); restaging. Milestone 8: Gemcitabine after surgery: 8 weeks Gemcitabine (chemotherapy); restaging; 8 weeks Gemcitabine (chemotherapy); restaging.
Milestone 9: No additional therapy after surgery. Milestone 10: After surgery no additional treatment. | 130 |
| Total | 130 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 85 |
| Overall Study | Physician Decision | 99 |
Baseline characteristics
| Characteristic | Milestones Related to Therapy |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 72 Participants |
| Age, Categorical Between 18 and 65 years | 58 Participants |
| Age, Continuous | 65.1 years STANDARD_DEVIATION 8.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 124 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 122 Participants |
| Region of Enrollment United States | 130 participants |
| Sex: Female, Male Female | 55 Participants |
| Sex: Female, Male Male | 75 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 85 / 130 |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 50 / 130 |
Outcome results
Primary
Number of Subjects Completing Therapy Including Surgical Resection.
This outcome measure is the number of subjects completing therapy up to and including surgical resection. In this context, surgical excision of residual tumor is an option in the progression of usual care. Surgery was contraindicated for some participants. This measure is the number of subject who were eligible for and completed the surgical procedure.
Time frame: At time of surgery (approximately 10 to 20 weeks after screening)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Milestones Related to Usual Therapy | Number of Subjects Completing Therapy Including Surgical Resection. | 107 Participants |
Secondary
Histologic Response to Targeted Chemotherapeutic Regimens in Resected Tumors.
The number of tumors showing a histologic response. Histological response will be measured using the Ryan Score method as defined by the American Joint Committee on Cancer, 7th edition (see Edge, 2010). Grading categories are defined as: Grade 0 (complete response); Grade 1 (near complete response); Grade 2 (partial response); and Grade 3 (poor or no response).
Time frame: At time of surgery (approximately 10 to 20 weeks after screening)
Population: Pathology results were not reported for two subject.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Milestones Related to Usual Therapy | Histologic Response to Targeted Chemotherapeutic Regimens in Resected Tumors. | Complete Response | 2 Participants |
| Milestones Related to Usual Therapy | Histologic Response to Targeted Chemotherapeutic Regimens in Resected Tumors. | Near Complete Response | 17 Participants |
| Milestones Related to Usual Therapy | Histologic Response to Targeted Chemotherapeutic Regimens in Resected Tumors. | Partial Response | 44 Participants |
| Milestones Related to Usual Therapy | Histologic Response to Targeted Chemotherapeutic Regimens in Resected Tumors. | Poor or No Response | 42 Participants |
| Milestones Related to Usual Therapy | Histologic Response to Targeted Chemotherapeutic Regimens in Resected Tumors. | Results Not Available | 2 Participants |
Secondary
Overall Survival in Months
This measure is the median time of survival (in months) at five years from the initiation of therapy. Results will be presented for two cohorts: subjects completing neoadjuvant therapy and surgical resection; and subjects completing neoadjuvant therapy but without surgical resection.
Time frame: 5 years
Population: Results will be presented for two cohorts: subjects completing neoadjuvant therapy and surgical resection; and subjects completing neoadjuvant therapy but without surgical resection.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Milestones Related to Usual Therapy | Overall Survival in Months | 45 Months |
| Milestones Related to Therapy (Non-Resected) | Overall Survival in Months | 11 Months |
Secondary
Progression-free Survival
This measure is the number of subjects not experiencing tumor progression at five years from initiating therapy.
Time frame: 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Milestones Related to Usual Therapy | Progression-free Survival | 36 Participants |
Secondary
Use of Biomarkers to Determine Course of Treatment
The number of subjects for whom a biomarker (i.e., molecular profile) was used to determine the course of treatment.
Time frame: Initiation of therapy (approximately 4 to 12 weeks after screening) until surgery (approximately 10 to 20 weeks after screening)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Milestones Related to Usual Therapy | Use of Biomarkers to Determine Course of Treatment | 92 Participants |