New and Emerging Therapies for the Treatment of Resectable, Borderline Resectable, or Locally Advanced Pancreatic Cancer, PIONEER-Panc Study

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Borderline Resectable Pancreatic Adenocarcinoma; Resectable Pancreatic Ductal Adenocarcinoma; Locally Advanced Pancreatic Ductal Adenocarcinoma
• Intervention / Treatment: Radiation: Radiation Therapy; Drug: Cisplatin; Drug: Gemcitabine; Drug: Nab-paclitaxel; Drug: Fluorouracil; Drug: Leucovorin; Drug: Oxaliplatin; Drug: Irinotecan

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 105
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Eugene J. Koay; Phone Number: 713-563-2381; Email: ekoay@mdanderson.org

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center
      • Principal Investigator: Eugene J. Koay
      • Contact: Eugene J. Koay; Phone Number: 713-563-2381

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• TREATMENT NAIVE RESECTABLE PDAC COHORT: Pathologically proven adenocarcinoma of the pancreas by cytology or biopsy
• TREATMENT NAIVE RESECTABLE PDAC COHORT: Confirmation of clinical stage of resectable
• TREATMENT NAIVE RESECTABLE PDAC COHORT: No prior chemotherapy or radiation therapy for PDAC
• TREATMENT NAIVE RESECTABLE PDAC COHORT: No current use of immunosuppressive medication
• TREATMENT NAIVE RESECTABLE PDAC COHORT: Not pregnant and not nursing, for women of childbearing potential, a negative urine or blood pregnancy test done =< 7 days prior to registration is required
• TREATMENT NAIVE RESECTABLE PDAC COHORT: Life expectancy greater than 6 months
• TREATMENT NAIVE RESECTABLE PDAC COHORT: Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• TREATMENT NAIVE RESECTABLE PDAC COHORT: Absolute neutrophil count (ANC) >= 1,500/mm^3
• TREATMENT NAIVE RESECTABLE PDAC COHORT: Platelet count >= 100,000/mm^3
• TREATMENT NAIVE RESECTABLE PDAC COHORT: Creatinine =< 1.5 x upper limit of normal (ULN)
• TREATMENT NAIVE RESECTABLE PDAC COHORT: Calculated (Calc.) creatinine clearance > 45 mL/min
• TREATMENT NAIVE RESECTABLE PDAC COHORT: Total bilirubin =< 2.0 mg/dL
• TREATMENT NAIVE RESECTABLE PDAC COHORT: Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)
• TREATMENT NAIVE RESECTABLE PDAC COHORT: Hemoglobin >= 8.0 mg/dL
• PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Pathologically proven adenocarcinoma of the pancreas by cytology or biopsy
• PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Confirmation of clinical stage of resectable
• PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Prior chemotherapy for PDAC is allowed, as long as the regimen is considered a standard regimen for PDAC (e.g., gemcitabine, gemcitabine-cisplatin, gemcitabine/nab-paclitaxel, gemcitabine/capecitabine, FOLFIRINOX). This should be discussed with the study principal investigators (PIs) prior to enrollment to ensure the regimen for a given patient is acceptable
• PREVIOUSLY TREATED RESECTABLE PDAC COHORT: No current use of immunosuppressive medication
• PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Not pregnant and not nursing, For women of childbearing potential, a negative urine or blood pregnancy test done ≤ 7 days prior to registration is required
• PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Life expectancy greater than 6 months
• PREVIOUSLY TREATED RESECTABLE PDAC COHORT: ECOG performance status 0 or 1
• PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Absolute neutrophil count (ANC) >= 1,500/mm^3
• PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Platelet count >= 100,000/mm^3
• PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Creatinine =< 1.5 x upper limit of normal (ULN)
• PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Calc. creatinine clearance > 45 mL/min
• PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Total bilirubin =< 2.0 mg/dL
• PREVIOUSLY TREATED RESECTABLE PDAC COHORT: AST/ALT =< 2.5 x upper limit of normal (ULN)
• PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Hemoglobin >= 8.0 mg/dL
• TREATMENT NAIVE BORDERLINE RESECTABLE PDAC COHORT: Pathologically proven adenocarcinoma of the pancreas by cytology or biopsy
• TREATMENT NAIVE BORDERLINE RESECTABLE PDAC COHORT: Confirmation of clinical stage of borderline resectable
• TREATMENT NAIVE BORDERLINE RESECTABLE PDAC COHORT: No prior chemotherapy or radiation therapy for PDAC
• TREATMENT NAIVE BORDERLINE RESECTABLE PDAC COHORT: No current use of immunosuppressive medication
• TREATMENT NAIVE BORDERLINE RESECTABLE PDAC COHORT: Not pregnant and not nursing, For women of childbearing potential, a negative urine or blood pregnancy test done ≤ 7 days prior to registration is required
• TREATMENT NAIVE BORDERLINE RESECTABLE PDAC COHORT: Life expectancy greater than 6 months
• TREATMENT NAIVE BORDERLINE RESECTABLE PDAC COHORT: ECOG performance status 0 or 1
• TREATMENT NAIVE BORDERLINE RESECTABLE PDAC COHORT: Absolute neutrophil count (ANC) >= 1,500/mm^3
• TREATMENT NAIVE BORDERLINE RESECTABLE PDAC COHORT: Platelet count >= 100,000/mm^3
• TREATMENT NAIVE BORDERLINE RESECTABLE PDAC COHORT: Creatinine =< 1.5 x upper limit of normal (ULN)
• TREATMENT NAIVE BORDERLINE RESECTABLE PDAC COHORT: Calc. creatinine clearance > 45 mL/min
• TREATMENT NAIVE BORDERLINE RESECTABLE PDAC COHORT: Total bilirubin =< 2.0 mg/dL
• TREATMENT NAIVE BORDERLINE RESECTABLE PDAC COHORT: AST/ALT =< 2.5 x upper limit of normal (ULN)
• TREATMENT NAIVE BORDERLINE RESECTABLE PDAC COHORT: Hemoglobin >= 8.0 mg/dL
• PREVIOUSLY TREATED BORDERLINE RESECTABLE PDAC COHORT: Pathologically proven adenocarcinoma of the pancreas by cytology or biopsy
• PREVIOUSLY TREATED BORDERLINE RESECTABLE PDAC COHORT: Confirmation of clinical stage of borderline resectable
• PREVIOUSLY TREATED BORDERLINE RESECTABLE PDAC COHORT: Prior chemotherapy for PDAC is allowed, as long as the regimen is considered a standard regimen for PDAC (e.g., gemcitabine, gemcitabine-cisplatin, gemcitabine/nab-paclitaxel, gemcitabine/capecitabine, FOLFIRINOX). This should be discussed with the study PIs prior to enrollment to ensure the regimen for a given patient is acceptable
• PREVIOUSLY TREATED BORDERLINE RESECTABLE PDAC COHORT: No current use of immunosuppressive medication
• PREVIOUSLY TREATED BORDERLINE RESECTABLE PDAC COHORT: Not pregnant and not nursing, For women of childbearing potential, a negative urine or blood pregnancy test done =< 7 days prior to registration is required
• PREVIOUSLY TREATED BORDERLINE RESECTABLE PDAC COHORT: Life expectancy greater than 6 months
• PREVIOUSLY TREATED BORDERLINE RESECTABLE PDAC COHORT: ECOG performance status 0 or 1
• PREVIOUSLY TREATED BORDERLINE RESECTABLE PDAC COHORT: Absolute neutrophil count (ANC) >= 1,500/mm^3
• PREVIOUSLY TREATED BORDERLINE RESECTABLE PDAC COHORT: Platelet count >= 100,000/mm^3
• PREVIOUSLY TREATED BORDERLINE RESECTABLE PDAC COHORT: Creatinine =< 1.5 x upper limit of normal (ULN)
• PREVIOUSLY TREATED BORDERLINE RESECTABLE PDAC COHORT: Calc. creatinine clearance > 45 mL/min
• PREVIOUSLY TREATED BORDERLINE RESECTABLE PDAC COHORT: Total bilirubin =< 2.0 mg/dL
• PREVIOUSLY TREATED BORDERLINE RESECTABLE PDAC COHORT: AST/ALT =< 2.5 x upper limit of normal (ULN)
• PREVIOUSLY TREATED BORDERLINE RESECTABLE PDAC COHORT: Hemoglobin >= 8.0 mg/dL
• TREATMENT NAIVE LOCALLY ADVANCED PDAC COHORT: Pathologically proven adenocarcinoma of the pancreas by cytology or biopsy
• TREATMENT NAIVE LOCALLY ADVANCED PDAC COHORT: Confirmation of clinical stage of locally advanced
• TREATMENT NAIVE LOCALLY ADVANCED PDAC COHORT: No prior chemotherapy or radiation therapy for PDAC
• TREATMENT NAIVE LOCALLY ADVANCED PDAC COHORT: Pregnancy and Nursing Status: Not pregnant and not nursing, For women of childbearing potential, a negative urine or blood pregnancy test done ≤ 7 days prior to registration is required
• TREATMENT NAIVE LOCALLY ADVANCED PDAC COHORT: Life expectancy greater than 6 months
• TREATMENT NAIVE LOCALLY ADVANCED PDAC COHORT: ECOG performance status 0 or 1
• TREATMENT NAIVE LOCALLY ADVANCED PDAC COHORT: Absolute neutrophil count (ANC) >= 1,500/mm^3
• TREATMENT NAIVE LOCALLY ADVANCED PDAC COHORT: Platelet count >= 100,000/mm^3
• TREATMENT NAIVE LOCALLY ADVANCED PDAC COHORT: Creatinine =< 1.5 x upper limit of normal (ULN)
• TREATMENT NAIVE LOCALLY ADVANCED PDAC COHORT: Calc. creatinine clearance > 45 mL/min
• TREATMENT NAIVE LOCALLY ADVANCED PDAC COHORT: Total bilirubin =< 2.0 mg/dL
• TREATMENT NAIVE LOCALLY ADVANCED PDAC COHORT: AST/ALT =< 2.5 x upper limit of normal (ULN)
• TREATMENT NAIVE LOCALLY ADVANCED PDAC COHORT: Hemoglobin >= 8.0 mg/dL
• PREVIOUSLY TREATED LOCALLY ADVANCED PDAC COHORT: Pathologically proven adenocarcinoma of the pancreas by cytology or biopsy
• PREVIOUSLY TREATED LOCALLY ADVANCED PDAC COHORT: Confirmation of clinical stage of locally advanced
• PREVIOUSLY TREATED LOCALLY ADVANCED PDAC COHORT: Prior chemotherapy for PDAC is allowed, as long as the regimen is considered a standard regimen for PDAC (e.g., gemcitabine, gemcitabine-cisplatin, gemcitabine/nab-paclitaxel, gemcitabine/capecitabine, FOLFIRINOX). This should be discussed with the study PIs prior to enrollment to ensure the regimen for a given patient is acceptable
• PREVIOUSLY TREATED LOCALLY ADVANCED PDAC COHORT: No current use of immunosuppressive medication
• PREVIOUSLY TREATED LOCALLY ADVANCED PDAC COHORT: Not pregnant and not nursing, For women of childbearing potential, a negative urine or blood pregnancy test done =< 7 days prior to registration is required
• PREVIOUSLY TREATED LOCALLY ADVANCED PDAC COHORT: Life expectancy greater than 6 months
• PREVIOUSLY TREATED LOCALLY ADVANCED PDAC COHORT: ECOG performance status 0 or 1
• PREVIOUSLY TREATED LOCALLY ADVANCED PDAC COHORT: Absolute neutrophil count (ANC) >= 1,500/mm^3
• PREVIOUSLY TREATED LOCALLY ADVANCED PDAC COHORT: Platelet count >= 100,000/mm^3
• PREVIOUSLY TREATED LOCALLY ADVANCED PDAC COHORT: Creatinine =< 1.5 x upper limit of normal (ULN)
• PREVIOUSLY TREATED LOCALLY ADVANCED PDAC COHORT: Calc. creatinine clearance > 45 mL/min
• PREVIOUSLY TREATED LOCALLY ADVANCED PDAC COHORT: Total bilirubin =< 2.0 mg/dL
• PREVIOUSLY TREATED LOCALLY ADVANCED PDAC COHORT: AST/ALT =< 2.5 x upper limit of normal (ULN)
• PREVIOUSLY TREATED LOCALLY ADVANCED PDAC COHORT: Hemoglobin >= 8.0 mg/dL

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

  • Patients who have been vaccinated for hepatitis B and do not have a history of infection are eligible
• 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

  • Patients who have been vaccinated for hepatitis B and do not have a history of infection are eligible
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control arm GroupI(mFOLFIRINOX); Patients receive mFOLFIRINOX for 3 months before and after surgery in the absence of disease progression or unacceptable toxicity.	Drug: Fluorouracil; Given IV; Other Names: 5-Fluracil; Fluracil; 5 Fluorouracil; 5 Fluorouracilum; 5 FU; 5-Fluoro-2,4(1H, 3H)-pyrimidinedione; 5-Fluorouracil; 5-Fu; 5FU; AccuSite; Carac; Fluoro Uracil; Fluouracil; Flurablastin; Fluracedyl; Fluril; Fluroblastin; Ribofluor; Ro 2-9757; Ro-2-9757; Drug: Leucovorin; Given IV; Other Names: Folinic acid; Drug: Oxaliplatin; Given IV; Other Names: 1-OHP; Dacotin; Dacplat; Eloxatin; Ai Heng; Aiheng; Diaminocyclohexane Oxalatoplatinum; Eloxatine; JM-83; Oxalatoplatin; Oxalatoplatinum; RP 54780; RP-54780; SR-96669; Drug: Irinotecan; Given IV
Active Comparator: Control arm GroupII(chemotherapy, FOLFIRINOX); 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.	Drug: Cisplatin; Given IV; Other Names: CDDP; Cis-diamminedichloridoplatinum; Cismaplat; Cisplatinum; Neoplatin; Platinol; Abiplatin; Blastolem; Briplatin; Cis-diammine-dichloroplatinum; Cis-diamminedichloro Platinum (II); Cis-diamminedichloroplatinum; Cis-dichloroammine Platinum (II); Cis-platinous Diamine Dichloride; Cis-platinum; Cis-platinum II; Cis-platinum II Diamine Dichloride; Cisplatina; Cisplatyl; Citoplatino; Citosin; Cysplatyna; DDP; Lederplatin; Metaplatin; Placis; Plastistil; Platamine; Platiblastin; Platiblastin-S; Platinex; Platinol- AQ; Platinol-AQ; Platinol-AQ VHA Plus; Platinoxan; Platinum; Platinum Diamminodichloride; Platiran; Platistin; Platosin; Peyrone''s Chloride; Peyrone''s Salt; Drug: Gemcitabine; Given IV; Other Names: dFdCyd; dFdC; Difluorodeoxycytidine; Drug: Nab-paclitaxel; Given IV; Other Names: ABI-007; Abraxane; Albumin-bound Paclitaxel; ABI 007; Albumin-Stabilized Nanoparticle Paclitaxel; Nanoparticle Albumin-bound Paclitaxel; Nanoparticle Paclitaxel; Paclitaxel Albumin; paclitaxel albumin-stabilized nanoparticle formulation; Protein-bound Paclitaxel; Drug: Fluorouracil; Given IV; Other Names: 5-Fluracil; Fluracil; 5 Fluorouracil; 5 Fluorouracilum; 5 FU; 5-Fluoro-2,4(1H, 3H)-pyrimidinedione; 5-Fluorouracil; 5-Fu; 5FU; AccuSite; Carac; Fluoro Uracil; Fluouracil; Flurablastin; Fluracedyl; Fluril; Fluroblastin; Ribofluor; Ro 2-9757; Ro-2-9757; Drug: Leucovorin; Given IV; Other Names: Folinic acid; Drug: Oxaliplatin; Given IV; Other Names: 1-OHP; Dacotin; Dacplat; Eloxatin; Ai Heng; Aiheng; Diaminocyclohexane Oxalatoplatinum; Eloxatine; JM-83; Oxalatoplatin; Oxalatoplatinum; RP 54780; RP-54780; SR-96669; Drug: Irinotecan; Given IV
Active Comparator: Control arm GroupIII(FOLFIRINOX, radiation therapy); 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.	Radiation: Radiation Therapy; Undergo RT; Other Names: Cancer Radiotherapy; Irradiate; Irradiated; Irradiation; Radiation; Radiation Therapy, NOS; Radiotherapeutics; Radiotherapy; RT; Therapy, Radiation; Drug: Fluorouracil; Given IV; Other Names: 5-Fluracil; Fluracil; 5 Fluorouracil; 5 Fluorouracilum; 5 FU; 5-Fluoro-2,4(1H, 3H)-pyrimidinedione; 5-Fluorouracil; 5-Fu; 5FU; AccuSite; Carac; Fluoro Uracil; Fluouracil; Flurablastin; Fluracedyl; Fluril; Fluroblastin; Ribofluor; Ro 2-9757; Ro-2-9757; Drug: Leucovorin; Given IV; Other Names: Folinic acid; Drug: Oxaliplatin; Given IV; Other Names: 1-OHP; Dacotin; Dacplat; Eloxatin; Ai Heng; Aiheng; Diaminocyclohexane Oxalatoplatinum; Eloxatine; JM-83; Oxalatoplatin; Oxalatoplatinum; RP 54780; RP-54780; SR-96669; Drug: Irinotecan; Given IV
Active Comparator: Control arm GroupIV(chemotherapy,FOLFIRINOX,radiation therapy); 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.	Radiation: Radiation Therapy; Undergo RT; Other Names: Cancer Radiotherapy; Irradiate; Irradiated; Irradiation; Radiation; Radiation Therapy, NOS; Radiotherapeutics; Radiotherapy; RT; Therapy, Radiation; Drug: Cisplatin; Given IV; Other Names: CDDP; Cis-diamminedichloridoplatinum; Cismaplat; Cisplatinum; Neoplatin; Platinol; Abiplatin; Blastolem; Briplatin; Cis-diammine-dichloroplatinum; Cis-diamminedichloro Platinum (II); Cis-diamminedichloroplatinum; Cis-dichloroammine Platinum (II); Cis-platinous Diamine Dichloride; Cis-platinum; Cis-platinum II; Cis-platinum II Diamine Dichloride; Cisplatina; Cisplatyl; Citoplatino; Citosin; Cysplatyna; DDP; Lederplatin; Metaplatin; Placis; Plastistil; Platamine; Platiblastin; Platiblastin-S; Platinex; Platinol- AQ; Platinol-AQ; Platinol-AQ VHA Plus; Platinoxan; Platinum; Platinum Diamminodichloride; Platiran; Platistin; Platosin; Peyrone''s Chloride; Peyrone''s Salt; Drug: Gemcitabine; Given IV; Other Names: dFdCyd; dFdC; Difluorodeoxycytidine; Drug: Nab-paclitaxel; Given IV; Other Names: ABI-007; Abraxane; Albumin-bound Paclitaxel; ABI 007; Albumin-Stabilized Nanoparticle Paclitaxel; Nanoparticle Albumin-bound Paclitaxel; Nanoparticle Paclitaxel; Paclitaxel Albumin; paclitaxel albumin-stabilized nanoparticle formulation; Protein-bound Paclitaxel; Drug: Fluorouracil; Given IV; Other Names: 5-Fluracil; Fluracil; 5 Fluorouracil; 5 Fluorouracilum; 5 FU; 5-Fluoro-2,4(1H, 3H)-pyrimidinedione; 5-Fluorouracil; 5-Fu; 5FU; AccuSite; Carac; Fluoro Uracil; Fluouracil; Flurablastin; Fluracedyl; Fluril; Fluroblastin; Ribofluor; Ro 2-9757; Ro-2-9757; Drug: Leucovorin; Given IV; Other Names: Folinic acid; Drug: Oxaliplatin; Given IV; Other Names: 1-OHP; Dacotin; Dacplat; Eloxatin; Ai Heng; Aiheng; Diaminocyclohexane Oxalatoplatinum; Eloxatine; JM-83; Oxalatoplatin; Oxalatoplatinum; RP 54780; RP-54780; SR-96669; Drug: Irinotecan; Given IV
Active Comparator: Control arm GroupV(FOLFIRINOX, radiation therapy); 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	Radiation: Radiation Therapy; Undergo RT; Other Names: Cancer Radiotherapy; Irradiate; Irradiated; Irradiation; Radiation; Radiation Therapy, NOS; Radiotherapeutics; Radiotherapy; RT; Therapy, Radiation; Drug: Fluorouracil; Given IV; Other Names: 5-Fluracil; Fluracil; 5 Fluorouracil; 5 Fluorouracilum; 5 FU; 5-Fluoro-2,4(1H, 3H)-pyrimidinedione; 5-Fluorouracil; 5-Fu; 5FU; AccuSite; Carac; Fluoro Uracil; Fluouracil; Flurablastin; Fluracedyl; Fluril; Fluroblastin; Ribofluor; Ro 2-9757; Ro-2-9757; Drug: Leucovorin; Given IV; Other Names: Folinic acid; Drug: Oxaliplatin; Given IV; Other Names: 1-OHP; Dacotin; Dacplat; Eloxatin; Ai Heng; Aiheng; Diaminocyclohexane Oxalatoplatinum; Eloxatine; JM-83; Oxalatoplatin; Oxalatoplatinum; RP 54780; RP-54780; SR-96669; Drug: Irinotecan; Given IV
Active Comparator: Control arm GroupVI(chemotherapy,FOLFIRINOX,radiation therapy); 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	Radiation: Radiation Therapy; Undergo RT; Other Names: Cancer Radiotherapy; Irradiate; Irradiated; Irradiation; Radiation; Radiation Therapy, NOS; Radiotherapeutics; Radiotherapy; RT; Therapy, Radiation; Drug: Cisplatin; Given IV; Other Names: CDDP; Cis-diamminedichloridoplatinum; Cismaplat; Cisplatinum; Neoplatin; Platinol; Abiplatin; Blastolem; Briplatin; Cis-diammine-dichloroplatinum; Cis-diamminedichloro Platinum (II); Cis-diamminedichloroplatinum; Cis-dichloroammine Platinum (II); Cis-platinous Diamine Dichloride; Cis-platinum; Cis-platinum II; Cis-platinum II Diamine Dichloride; Cisplatina; Cisplatyl; Citoplatino; Citosin; Cysplatyna; DDP; Lederplatin; Metaplatin; Placis; Plastistil; Platamine; Platiblastin; Platiblastin-S; Platinex; Platinol- AQ; Platinol-AQ; Platinol-AQ VHA Plus; Platinoxan; Platinum; Platinum Diamminodichloride; Platiran; Platistin; Platosin; Peyrone''s Chloride; Peyrone''s Salt; Drug: Gemcitabine; Given IV; Other Names: dFdCyd; dFdC; Difluorodeoxycytidine; Drug: Nab-paclitaxel; Given IV; Other Names: ABI-007; Abraxane; Albumin-bound Paclitaxel; ABI 007; Albumin-Stabilized Nanoparticle Paclitaxel; Nanoparticle Albumin-bound Paclitaxel; Nanoparticle Paclitaxel; Paclitaxel Albumin; paclitaxel albumin-stabilized nanoparticle formulation; Protein-bound Paclitaxel; Drug: Fluorouracil; Given IV; Other Names: 5-Fluracil; Fluracil; 5 Fluorouracil; 5 Fluorouracilum; 5 FU; 5-Fluoro-2,4(1H, 3H)-pyrimidinedione; 5-Fluorouracil; 5-Fu; 5FU; AccuSite; Carac; Fluoro Uracil; Fluouracil; Flurablastin; Fluracedyl; Fluril; Fluroblastin; Ribofluor; Ro 2-9757; Ro-2-9757; Drug: Leucovorin; Given IV; Other Names: Folinic acid; Drug: Oxaliplatin; Given IV; Other Names: 1-OHP; Dacotin; Dacplat; Eloxatin; Ai Heng; Aiheng; Diaminocyclohexane Oxalatoplatinum; Eloxatine; JM-83; Oxalatoplatin; Oxalatoplatinum; RP 54780; RP-54780; SR-96669; Drug: Irinotecan; Given IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major pathological response rate	Major pathological response is any patient who has grade I or II treatment response. Grade I - 0% residual tumor cells in the specimen (pathologic complete response, grade II - 1 to < 5% residual tumor cells in the specimen.	12 weeks
Disease control rate	Measured as the proportion of patients without progression.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	Will be estimated using the Kaplan-Meier method. Comparisons of these time-to-event endpoints by important covariate subgroups will be made using the log-rank tests. Cox proportional hazards regression models will be explored to evaluate the associations between the time-to-event endpoints and covariates of interest.	From the date of treatment initiation to the date of disease progression, recurrence after surgery or death from any cause whichever occurs first, assessed up to 5 years
Overall survival	Will be estimated using the Kaplan-Meier method. Comparisons of these time-to-event endpoints by important covariate subgroups will be made using the log-rank tests. Cox proportional hazards regression models will be explored to evaluate the associations between the time-to-event endpoints and covariates of interest.	From treatment start till death or last follow-up if the patient is alive, assessed up to 5 years

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Eugene J Koay, M.D. Anderson Cancer Center

Publications and helpful links

General Publications

• Douglas JE, Liu S, Ma J, Wolff RA, Pant S, Maitra A, Tamm EP, Bhosale P, Katz MHG, Varadhachary GR, Koay EJ. PIONEER-Panc: a platform trial for phase II randomized investigations of new and emerging therapies for localized pancreatic cancer. BMC Cancer. 2022 Jan 3;22(1):14. doi: 10.1186/s12885-021-09095-7.

Helpful Links

• M D Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): April 18, 2023
• Primary Completion (Estimated): April 6, 2025
• Study Completion (Estimated): April 6, 2025

Study Registration Dates

• First Submitted: July 17, 2020
• First Submitted That Met QC Criteria: July 20, 2020
• First Posted (Actual): July 22, 2020

Study Record Updates

• Last Update Posted (Actual): October 3, 2023
• Last Update Submitted That Met QC Criteria: October 2, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Protective Agents; Antineoplastic Agents, Phytogenic; Topoisomerase Inhibitors; Micronutrients; Vitamins; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Paclitaxel; Cisplatin; Fluorouracil; Oxaliplatin; Leucovorin; Irinotecan; Albumin-Bound Paclitaxel; Gemcitabine
• Other Study ID Numbers: 2020-0075 (Other Identifier: M D Anderson Cancer Center); NCI-2020-04886 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No