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NCT02839343 · CITED IN SOURCE DOCUMENTS

Combination Chemotherapy With or Without Hypofractionated Radiation Therapy Before Surgery in Treating Patients With Pancreatic Cancer

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE2
Status at capture
UNKNOWN
Registry last update
2022-05-24

This randomized phase II trial studies how well combination chemotherapy (mFOLFIRINOX) with or without hypofractionated radiation therapy before surgery works in patients with pancreatic cancer that can be removed by surgery. Drugs used in combination chemotherapy, such as oxaliplatin, leucovorin calcium, fluorouracil, and irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. It is not yet known if combination chemotherapy is more effective with or without hypofractionated radiation therapy before surgery in treating patients with pancreatic cancer.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Overall Survival (OS) Rate

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outcome · POSTED

Residual Tumor (R)0 Resection Rate

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outcome · POSTED

Event-free Survival

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outcome · POSTED

Pathologic Complete Rate (pCR) Rate

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outcome · POSTED

Incidence of Adverse Events Assessed Per Common Terminology Criteria for Adverse Events (CTCAE) Version 4 and the Patient-Reported Outcomes Version of the CTCAE

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility Criteria
Inclusion Criteria: * Confirmation of radiographic stage as borderline resectable disease by real-time Alliance central radiographic review * No prior chemotherapy or radiation for pancreatic cancer * No definitive resection of pancreatic cancer * Chronic concomitant treatment with strong inhibitors of cytochrome p450, family 3, subfamily a, polypeptide 4 gene (CYP3A4) is not allowed on this study; patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to registration on the study * Chronic concomitant treatment with strong CYP3A4 inducers is not allowed; patients must discontinue the drug 14 days prior to the start of study treatment * No grade \>= 2 neuropathy * No known Gilbert's syndrome or known homozygosity for UGAT1A1\*28 polymorphism * No uncontrolled gastric ulcer disease (grade 3 gastric ulcer disease) within 28 days of registration * Not pregnant and not nursing; for women of childbearing potential only, a negative pregnancy test done =\< 7 days prior to registration is required * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 * Absolute neutrophil count (ANC) \>= 1,500/mm\^3 * Platelet count \>= 100,000/mm\^3 * Creatinine =\< 1.5 x upper limit of normal (ULN) or * Calculated (calc.) creatinine clearance \> 45 mL/min * Total bilirubin =\< 2.0 mg/dL * Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) =\< 2.5 X upper limit of normal (ULN)
healthy Volunteers
false
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    Patients receive 8 cycles of mFOLFIRINOX. One cycle is 14 days. mFOLFIRINOX consists of oxaliplatin, irinotecan, leucovorin and 5-FU. Patients undergo surgery and receive 4 cycles of FOLFOX 4-12 weeks after surgery. FOLFOX consists of oxaliplatin, leucovorin and 5-FU.
    intervention Names
    1. Procedure: surgery
    2. Drug: mFOLFIRINOX
    3. Drug: FOLFOX
    label
    mFOLFIRINOX + surgery + FOLFOX
    type
    EXPERIMENTAL
  2. description
    Patients receive 7 cycles of mFOLFIRINOX. One cycle is 14 days. mFOLFIRINOX consists of oxaliplatin, irinotecan, leucovorin and 5-FU. Patients receive radiation therapy then undergo surgery and receive 4 cycles of FOLFOX 4-12 weeks after surgery. FOLFOX consists of oxaliplatin, leucovorin and 5-FU.
    intervention Names
    1. Radiation: radiation therapy
    2. Procedure: surgery
    3. Drug: mFOLFIRINOX
    4. Drug: FOLFOX
    label
    mFOLFIRINOX + radiation + surgery + FOLFOX
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. mFOLFIRINOX + radiation + surgery + FOLFOX
    name
    radiation therapy
    type
    RADIATION
  2. arm Group Labels
    1. mFOLFIRINOX + radiation + surgery + FOLFOX
    2. mFOLFIRINOX + surgery + FOLFOX
    name
    surgery
    type
    PROCEDURE
  3. arm Group Labels
    1. mFOLFIRINOX + radiation + surgery + FOLFOX
    2. mFOLFIRINOX + surgery + FOLFOX
    description
    oxaliplatin IV, irinotecan IV, leucovorin IV and 5-FU IV
    name
    mFOLFIRINOX
    type
    DRUG
  4. arm Group Labels
    1. mFOLFIRINOX + radiation + surgery + FOLFOX
    2. mFOLFIRINOX + surgery + FOLFOX
    description
    oxaliplatin IV, leucovorin IV and 5-FU IV
    name
    FOLFOX
    type
    DRUG
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
126
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    Defined as the percentage of patients who are alive at 18 months after randomization divided by the total number of evaluable patients in each arm. An evaluable patient is defined as any patient who signed informed consent, deemed eligible by central review and received any protocol-defined treatment. 95% confidence interval will be estimated based on standard method. Chi-squared test (or Fisher's exact test if the data in contingency table is sparse) will be used to compare 18 month OS rates among treatment arms. OS within each arm will be summarized by Kaplan-Meier method. Median, 1-year and 2-year rates will be estimated based on Kaplan-Meier curves.
    measure
    Overall Survival (OS) Rate
    time Frame
    18 months
secondary Outcomes
  1. description
    Defined as the percentage of patients in whom an achieved R0 resection was achieved during surgery.
    measure
    Residual Tumor (R)0 Resection Rate
    time Frame
    24 months
  2. description
    Defined as time from randomization to the first documentation of event where events considered are 1) disease progression, per RECIST, prior to surgery, 2) surgery with R2 resection, 3) recurrent disease following surgery, or 4) death due to any cause. Will be estimated using the method of Kaplan-Meier in each arm and compared between treatment groups using the log-rank test. The correlation between pathologic complete response (pCR) status and event-free survival time will be assessed by Cox model with landmark approach.
    measure
    Event-free Survival
    time Frame
    4 years and 7 months
  3. description
    Defined as the percentage of patients in whom a pCR was confirmed by histopathologic review of the surgical specimen. Chi-square test (or Fisher's exact test if the data in contingency table is sparse) will be used to compare pCR resection rate between two treatment arms. Sensitivity analysis will be conducted among patients in cohort 1) and cohort 2). The association between pCR rate and OS/progression free survival (PFS) will be assessed by log-rank test and Cox model.
    measure
    Pathologic Complete Rate (pCR) Rate
    time Frame
    24 months
  4. description
    Overall adverse event rates will be compared between treatment groups using Chi-square test (or Fisher's exact test if the data in contingency table is sparse).
    measure
    Incidence of Adverse Events Assessed Per Common Terminology Criteria for Adverse Events (CTCAE) Version 4 and the Patient-Reported Outcomes Version of the CTCAE
    time Frame
    1 year
Full study description
brief Summary
This randomized phase II trial studies how well combination chemotherapy (mFOLFIRINOX) with or without hypofractionated radiation therapy before surgery works in patients with pancreatic cancer that can be removed by surgery. Drugs used in combination chemotherapy, such as oxaliplatin, leucovorin calcium, fluorouracil, and irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. It is not yet known if combination chemotherapy is more effective with or without hypofractionated radiation therapy before surgery in treating patients with pancreatic cancer.
detailed Description
PRIMARY OBJECTIVES: I. To evaluate and estimate 18 months overall survival (OS) rate of patients with borderline resectable pancreatic ductal adenocarcinoma (PDAC) receiving neoadjuvant therapy. SECONDARY OBJECTIVES: I. To evaluate and estimate the R0 resection rates in patients receiving each of the two multimodality treatment regimens. II. To evaluate and estimate the event-free survival in patients receiving each of the two multimodality treatment regimens. III. To evaluate and estimate the pathologic compete response (pCR) rates in patients receiving each of the two multimodality treatment regimens. IV. To assess the adverse events (AE) profile and safety of each treatment arm. TERTIARY OBJECTIVES: I. To test the effect of the rs2853564 vitamin D receptor (VDR) variant on OS rate and discover novel candidate genes associated with OS and severe toxicity of chemotherapy by using genome-wide genotyping approaches. II. To evaluate risk classification previously developed by Koay et al using normalized area under the enhancement curve (NAUC). III. To access prognostic value of NAUC ratio defined as post-neoadjuvant NAUC divided by pre-neoadjuvant therapy NAUC. IV. To evaluate risk classification previously developed by Koay et al using delta measure. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive oxaliplatin intravenously (IV) over 2 hours, irinotecan IV over 90 minutes, and leucovorin calcium IV over 2 hours on day 1. Patients also receive fluorouracil IV continuously over 46-48 hours on days 1-2. Treatment repeats every 14 days for 8 courses in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive oxaliplatin intravenously (IV) over 2 hours, irinotecan IV over 90 minutes, and leucovorin calcium IV over 2 hours on day 1. Patients also receive fluorouracil IV continuously over 46-48 hours on days 1-2. Treatment repeats every 14 days for 7 courses in the absence of disease progression or unacceptable toxicity. Patients receive either stereotactic body radiation therapy (SBRT) or hypofractionated image guided radiation therapy (HIGRT) on days 1-5 of course 8. SURGERY Within 4 to 8 weeks after the last dose of chemotherapy (arm A) or of radiation (arm B), patients considered surgical candidates for resection (after central review) will undergo surgery at the registering institution. ADJUVANT CHEMOTHERAPY Within 4-12 weeks from the date of surgery, patients will receive oxaliplatin IV over 2 hours and leucovorin IV over 2 hours on day 1. Patients also receive fluorouracil IV continuously over 46-48 hours on days 1-2. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 16 weeks for 2 years, then every 6 months for 5 years.
Source references
references
  1. citation
    Snyder RA, Zemla TJ, Shi Q, Segovia D, Ahmad SA, O'Reilly EM, Herman JM, Katz MHG. Postoperative Adverse Events Following Neoadjuvant Therapy and Surgery for Borderline Resectable Pancreatic Cancer in a Phase 2 Clinical Trial (Alliance A021501). Ann Surg Oncol. 2024 Oct;31(10):7033-7042. doi: 10.1245/s10434-024-15670-6. Epub 2024 Jul 15.
    pmid
    39008208
    type
    DERIVED
  2. citation
    Tchelebi LT, Segovia D, Smith K, Shi Q, Fitzgerald TJ, Chuong MD, Zemla TJ, O'Reilly EM, Meyerhardt JA, Koay EJ, Lowenstein J, Shergill A, Katz MHG, Herman JM. Radiation Therapy Quality Assurance Analysis of Alliance A021501: Preoperative mFOLFIRINOX or mFOLFIRINOX Plus Hypofractionated Radiation Therapy for Borderline Resectable Adenocarcinoma of the Pancreas. Int J Radiat Oncol Biol Phys. 2024 Sep 1;120(1):111-119. doi: 10.1016/j.ijrobp.2024.03.013. Epub 2024 Mar 15.
    pmid
    38492812
    type
    DERIVED
  3. citation
    Katz MHG, Shi Q, Meyers J, Herman JM, Chuong M, Wolpin BM, Ahmad S, Marsh R, Schwartz L, Behr S, Frankel WL, Collisson E, Leenstra J, Williams TM, Vaccaro G, Venook A, Meyerhardt JA, O'Reilly EM. Efficacy of Preoperative mFOLFIRINOX vs mFOLFIRINOX Plus Hypofractionated Radiotherapy for Borderline Resectable Adenocarcinoma of the Pancreas: The A021501 Phase 2 Randomized Clinical Trial. JAMA Oncol. 2022 Sep 1;8(9):1263-1270. doi: 10.1001/jamaoncol.2022.2319.
    pmid
    35834226
    type
    DERIVED
  4. citation
    Katz MHG, Ou FS, Herman JM, Ahmad SA, Wolpin B, Marsh R, Behr S, Shi Q, Chuong M, Schwartz LH, Frankel W, Collisson E, Koay EJ, Hubbard JM, Leenstra JL, Meyerhardt J, O'Reilly E; Alliance for Clinical Trials on Oncology. Alliance for clinical trials in oncology (ALLIANCE) trial A021501: preoperative extended chemotherapy vs. chemotherapy plus hypofractionated radiation therapy for borderline resectable adenocarcinoma of the head of the pancreas. BMC Cancer. 2017 Jul 27;17(1):505. doi: 10.1186/s12885-017-3441-z.
    pmid
    28750659
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
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      1. context
        Updated: February 12, 2025
        datetime
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        February 12, 2025

    Preserved source evidence · Not medical advice