PIONEER-Panc: Phase II Investigations of New and Emerging Therapies for Pancreatic Cancer
PIONEER-Panc: Phase II Investigations of New and Emerging Therapies for Pancreatic Cancer
This is a phase II study using the Bayesian platform design. There are three clinical stage groups of localized pancreatic cancer: resectable, borderline resectable, and locally advanced disease. Each stage group will have a defined standard of care chemotherapy regimen for a control arm, serving as a basis of comparison. Each group may have one or more experimental arms. Experimental arms may be added to the platform over time, and the effects of the experimental treatments will be tested against the controls for each group.
PRIMARY OBJECTIVES:
I. To estimate major pathological response rate. (Resectable and borderline resectable groups [treatment naive or previously treated]) II. To estimate 6-month disease control rate. (Locally advanced groups [treatment naive or previously treated])
SECONDARY OBJECTIVES:
I. To measure progression free survival and overall survival. (Resectable and borderline resectable groups [treatment naive or previously treated]) II. To measure progression free survival and overall survival. (Locally advanced groups [treatment naive or previously treated])
EXPLORATORY OBJECTIVES:
I. To benchmark tissue acquisition protocols for deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) analysis in pancreatic ductal adenocarcinoma (PDAC).
II. To demonstrate concordance of cell free DNA detected mutations to those detected in the tumor-derived DNA in PDAC.
III. To demonstrate response through exosome and circulating tumor DNA. IV. To demonstrate response through the quantification of the immune activation by analyzing T and B cells, peripheral blood mononuclear cells, and tissue biopsies.
V. To derive organoids from human PDAC and measure drug response in vitro. VI. To analyze the tumor microenvironment through immunohistochemistry (IHC) and hypoxia staining.
VII. To associate prognosis of patients with baseline and follow-up quantitative computed tomography (CT) image based analysis.
VIII. To associate clinical and pathological outcomes of patients with changes in radiomic measurements.
IX. To correlate quality of life for patients on standard and experimental therapies with laboratory, radiological, pathological, and clinical characteristics.
OUTLINE:Patients are assigned to different groups, and each group has a control arm. Within each group, the patient will be randomized to the appropriate control or an experimental arm. The control arms for the groups are:
Control arm for Group I (Treatment-naive resectable PDAC): Patients receive fluorouracil, irinotecan, leucovorin, and oxaliplatin (mFOLFIRINOX) for 3 months before and after surgery in the absence of disease progression or unacceptable toxicity.
Control arm for Group II (Previously-treated resectable PDAC): Patients receive gemcitabine, gemcitabine and nab-paclitaxel, gemcitabine and cisplatin, or FOLFIRINOX for up to 4 months in the absence of disease progression or unacceptable toxicity.
Control arm for Group III (Treatment-naive borderline resectable PDAC): Patients receive FOLFIRINOX for 4-6 months in the absence of disease progression or unacceptable toxicity. Patients may then undergo radiation therapy at the discretion of medical doctors.
Control arm for Group IV (Previously-treated borderline resectable PDAC): Patients receive gemcitabine, gemcitabine and nab-paclitaxel, gemcitabine and cisplatin, or FOLFIRINOX for 6 months in the absence of disease progression or unacceptable toxicity. Patients may then undergo radiation therapy at the discretion of medical doctors.
Control arm for Group V (Treatment-naive locally advanced PDAC): Patients receive FOLFIRINOX for 4-6 months in the absence of disease progression or unacceptable toxicity. Patients may then undergo radiation therapy at the discretion of medical doctors.
Control arm for Group VI (Previously-treated locally advanced PDAC): Patients receive gemcitabine, gemcitabine and nab-paclitaxel, gemcitabine and cisplatin, or FOLFIRINOX for 6 months in the absence of disease progression or unacceptable toxicity. Patients may then undergo radiation therapy at the discretion of medical doctors.
After completion of study treatment, patients are followed up every 16 weeks.
Inclusion Criteria:
Exclusion Criteria:
TREATMENT NAIVE RESECTABLE PDAC COHORT: Previous treatment for PDAC with chemotherapy or radiation
TREATMENT NAIVE RESECTABLE PDAC COHORT: Active malignancy, except basal cell carcinoma
TREATMENT NAIVE RESECTABLE PDAC COHORT: Staging other than resectable PDAC
TREATMENT NAIVE RESECTABLE PDAC COHORT: Known uncontrolled (grade >=2) or active gastric or duodenal ulcer disease within 30 days of enrollment
TREATMENT NAIVE RESECTABLE PDAC COHORT: Prior surgical resection of pancreatic tumor
TREATMENT NAIVE RESECTABLE PDAC COHORT: Known contraindication to iodine-based or gadolinium-based intravenous (IV) contrast
TREATMENT NAIVE RESECTABLE PDAC COHORT: Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes, second or third degree atrioventricular heart block without a permanent pacemaker in place)
TREATMENT NAIVE RESECTABLE PDAC COHORT: Class III or IV congestive heart failure as defined by the New York Heart Association functional classification system < 6 months prior to screening
TREATMENT NAIVE RESECTABLE PDAC COHORT: Known active, uncontrolled (high viral load) human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection
TREATMENT NAIVE RESECTABLE PDAC COHORT: Female patients who are pregnant of breastfeeding
TREATMENT NAIVE RESECTABLE PDAC COHORT: Women of child-bearing potential and their male partners who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period. Acceptable methods of contraception are those that, alone or in combination, result in a failure rate of < 1% per year when used consistently and correctly
TREATMENT NAIVE RESECTABLE PDAC COHORT: Have significant psychiatric, social, or medical condition(s) that could increase the subject's risk, interfere with protocol adherence, or affect the subject's ability to give informed consent
PREVIOUSLY TREATED RESECTABLE PDAC COHORT: The patient is treatment naive
PREVIOUSLY TREATED RESECTABLE PDAC COHORT: The patient previously received radiation to the abdomen for any reason
PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Active malignancy, except basal cell carcinoma
PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Staging other than resectable PDAC at the time of diagnosis
PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Receiving any approved or investigational anti-neoplastic agent other than the chemotherapies specified in this protocol
PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Known uncontrolled (grade >= 2) or active gastric or duodenal ulcer disease within 30 days of enrollment
PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Prior surgical resection of pancreatic tumor
PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Known contraindication to iodine-based or gadolinium-based IV contrast
PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes, second or third degree atrioventricular heart block without a permanent pacemaker in place)
PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Class III or IV congestive heart failure as defined by the New York Heart Association functional classification system < 6 months prior to screening
PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Known active, uncontrolled (high viral load) HIV, hepatitis B or hepatitis C infection
PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Female patients who are pregnant of breastfeeding
PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Women of child-bearing potential and their male partners who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period. Acceptable methods of contraception are those that, alone or in combination, result in a failure rate of < 1% per year when used consistently and correctly
PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Have significant psychiatric, social, or medical condition(s) that could increase the subject's risk, interfere with protocol adherence, or affect the subject's ability to give informed consent
TREATMENT NAIVE BORDERLINE RESECTABLE PDAC COHORT: Previous treatment for PDAC with chemotherapy or radiation
TREATMENT NAIVE BORDERLINE RESECTABLE PDAC COHORT: Active malignancy, except basal cell carcinoma
TREATMENT NAIVE BORDERLINE RESECTABLE PDAC COHORT: Staging other than borderline resectable PDAC
TREATMENT NAIVE BORDERLINE RESECTABLE PDAC COHORT: Known uncontrolled (grade >= 2) or active gastric or duodenal ulcer disease within 30 days of enrollment
TREATMENT NAIVE BORDERLINE RESECTABLE PDAC COHORT: Prior surgical resection of pancreatic tumor
TREATMENT NAIVE BORDERLINE RESECTABLE PDAC COHORT: Known contraindication to iodine-based or gadolinium-based IV contrast
TREATMENT NAIVE BORDERLINE RESECTABLE PDAC COHORT: Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes, second or third degree atrioventricular heart block without a permanent pacemaker in place)
TREATMENT NAIVE BORDERLINE RESECTABLE PDAC COHORT: Class III or IV congestive hea