Testing Higher Dose Radiation Therapy for Locally Advanced Pancreatic Cancer
- Conditions
- Pancreas Cancer
- Interventions
- Radiation: Dose-escalated Radiation TherapyProcedure: Biopsy ProcedureProcedure: Computed TomographyProcedure: Magnetic Resonance ImagingOther: Questionnaire AdministrationRadiation: Radiation TherapyOther: Observation ActivityProcedure: Biospecimen Collection
- Registration Number
- NCT06958328
- Lead Sponsor
- NRG Oncology
- Brief Summary
This phase III trial compares the effect of dose-escalated radiation therapy to usual care in patients with locally advanced unresectable pancreatic ductal adenocarcinoma who have received an initial 4-6 months of chemotherapy. Usual care options include additional chemotherapy, observation, or standard lower-dose radiation therapy. These treatments may delay tumor growth but have not been shown to improve survival. Radiation therapy uses high energy X-rays to kill cancer cells and shrink tumors. Dose-escalated radiation therapy involves the precise delivery of higher doses to the tumor, often over a shorter period of time. This trial assesses whether using dose-escalated radiation therapy can prolong survival.
- Detailed Description
PRIMARY OBJECTIVE:
I. To evaluate whether dose-escalated radiation therapy (RT) improves 3-year overall survival (OS) compared to standard treatments without dose-escalated RT, in locally advanced pancreatic cancer patients without radiographic progression and with biochemical response after an initial interval of chemotherapy.
SECONDARY OBJECTIVES:
I. To evaluate and compare local progression between the two treatment arms. II. To evaluate and compare progression-free survival (PFS) between the two treatment arms.
III. To evaluate and compare chemotherapy-free interval between the two treatment arms.
IV. To evaluate and compare toxicity within and between the two treatment arms.
HEALTH-RELATED QUALITY-OF-LIFE (HRQOL) OBJECTIVES:
I. Primary: To compare Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) Total Score at 6 months between the two treatment arms.
II. Secondary: To compare nadir of HRQoL scores over course of study participation between the two treatment arms.
III. Secondary: To evaluate HRQoL scores over time between the two treatment arms.
EXPLORATORY OBJECTIVE:
I. Biospecimen collection for future correlative analyses.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I (STANDARD OF CARE): Patients are assigned to 1 of 3 treatment options per physician's decision.
OPTION 1: Patients continue to receive fluorouracil, irinotecan hydrochloride, leucovorin calcium, and oxaliplatin (FOLFIRINOX or modified FOLFIRINOX \[mFOLFIRINOX\]) or fluorouracil, liposomal irinotecan, leucovorin calcium, and oxaliplatin (NALIRIFOX) or gemcitabine/nab-paclitaxel per standard of care for a total of 6 months of treatment. Patients may continue treatment beyond 6 months at physician's discretion.
OPTION 2: Patients undergo standard dose radiation therapy once daily for 28 fractions and receive fluorouracil or capecitabine per standard of care during radiation therapy. After completing concurrent chemoradiation, patients who received less than 6 months of chemotherapy at study entry are encouraged to receive the remaining chemotherapy to total 6 months of chemotherapy. Patients may continue chemotherapy treatment beyond 6 months at physician's discretion.
OPTION 3: Patients undergo observation per standard of care. (It is recommended \[but not required\] that this option only be for patients that have already completed total 6 months chemotherapy pre-randomization.)
Additionally, patients undergo blood sample collection, computed tomography (CT), magnetic resonance imaging (MRI) and tumor tissue biopsy throughout the study.
ARM II (DOSE-ESCALATED RADIATION THERAPY): Patients undergo dose-escalated RT daily, every other day, or twice weekly for 5 fractions or daily for 25 fractions (with or without concurrent fluoropyrimidine). After completing dose-escalated RT, patients who received less than 6 months of chemotherapy at study entry are encouraged to receive the remaining chemotherapy to total 6 months of chemotherapy. Patients may continue chemotherapy treatment beyond 6 months at physician's discretion. Additionally, patients undergo blood sample collection, CT, MRI and tumor tissue biopsy throughout the study.
After completion of study treatment, patients are followed up every 3 months for 2 years then annually for 3 years.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 356
-
• At time of enrollment, the patient must have received 4-6 months of active chemotherapy with FOLFIRINOX (8-12 cycles) or NALIRIFOX (8-12 cycles) or gemcitabine/nab-paclitaxel (4-6 cycles) (1 regimen, no sequential chemotherapy). "Active chemotherapy" refers to time on chemotherapy not counting treatment breaks (i.e. if a patient had 1 month of chemotherapy followed by 1 month break, this would count as 1 month chemotherapy). Study registration must occur within 45 days of last day of chemotherapy cycle
- BASELINE PRE-ENTRY CHEMOTHERAPY REQUIREMENTS:
- Pathologically (histologically or cytologically) proven diagnosis of pancreatic ductal adenocarcinoma
- Locally advanced unresectable disease (as defined per the National Comprehensive Cancer Network [NCCN] guidelines and institutional tumor board review)
- Patients must have baseline pre-chemotherapy scans for staging. Options include: CT chest/abdomen/pelvis, CT chest/MRI abdomen/pelvis, or CT chest/CT pelvis/MRI abdomen performed prior to enrollment
- Age ≥ 18 years
- Performance status Eastern Cooperative Oncology Group (ECOG) 0-2
- Baseline CA19-9 with a normal bilirubin level (defined as ≤ 1.2 mg/dl)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x upper limit of normal (ULN)
- POST PRE-ENTRY CHEMOTHERAPY REQUIREMENTS:
- If baseline CA19-9 is elevated (defined as > 37 u/mL) the post-pre-entry chemotherapy CA19-9 must be less than 37 u/mL or a 50% decline from pre-chemotherapy level with absolute value less than 100u/mL
- If baseline CA19-9 is not elevated (defined as ≤ 37 u/mL) the post-pre-entry chemotherapy CA19-9 must remain ≤ 37 u/mL
- No active duodenal or gastric ulcers
- No direct tumor invasion of the bowel or stomach
- Restaging scans showing at least stable disease (no progression). Options for scans include: CT chest/abdomen/pelvis, CT chest/MRI abdomen/pelvis, or CT chest/CT pelvis/MRI abdomen performed prior to enrollment, with restaging CT showing at least stable disease
- Not pregnant and not nursing
- No cardiac condition that was the primary reason for hospitalization in the last 6 months
- New York Heart Association Functional Classification II or better (NYHA Functional Classification III/IV are not eligible) (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification.)
- HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm I (standard of care) Fluorouracil 1: Patients continue to receive fluorouracil, irinotecan hydrochloride, leucovorin calcium, and oxaliplatin or fluorouracil, liposomal irinotecan, leucovorin calcium, and oxaliplatin or gemcitabine/nab-paclitaxel per standard of care for a total of 6 months of treatment. Patients may continue treatment beyond 6 months at physician's discretion. 2: Patients undergo standard dose radiation therapy once daily for 28 fractions and receive fluorouracil or capecitabine per SOC during radiation therapy. After completing concurrent chemoradiation, patients who received less than 6 months of chemotherapy at study entry are encouraged to receive the remaining chemotherapy to total 6 months of chemotherapy. Patients may continue chemotherapy treatment beyond 6 months at physician's discretion. 3: Patients undergo observation per standard of care. \*patients undergo blood sample collection, computed tomography (CT), magnetic resonance imaging (MRI) and tumor tissue biopsy throughout the study. ARM II (DOSE-ESCALATED RADIATION THERAPY): Biopsy Procedure ): Patients undergo dose-escalated RT daily, every other day, or twice weekly for 5 fractions or daily for 25 fractions (with or without concurrent fluoropyrimidine). After completing dose-escalated RT, patients who received less than 6 months of chemotherapy at study entry are encouraged to receive the remaining chemotherapy to total 6 months of chemotherapy. Patients may continue chemotherapy treatment beyond 6 months at physician's discretion. Additionally, patients undergo blood sample collection, CT, MRI and tumor tissue biopsy throughout the study. After completion of study treatment, patients are followed up every 3 months for 2 years then annually for 3 years. ARM II (DOSE-ESCALATED RADIATION THERAPY): Computed Tomography ): Patients undergo dose-escalated RT daily, every other day, or twice weekly for 5 fractions or daily for 25 fractions (with or without concurrent fluoropyrimidine). After completing dose-escalated RT, patients who received less than 6 months of chemotherapy at study entry are encouraged to receive the remaining chemotherapy to total 6 months of chemotherapy. Patients may continue chemotherapy treatment beyond 6 months at physician's discretion. Additionally, patients undergo blood sample collection, CT, MRI and tumor tissue biopsy throughout the study. After completion of study treatment, patients are followed up every 3 months for 2 years then annually for 3 years. ARM II (DOSE-ESCALATED RADIATION THERAPY): Magnetic Resonance Imaging ): Patients undergo dose-escalated RT daily, every other day, or twice weekly for 5 fractions or daily for 25 fractions (with or without concurrent fluoropyrimidine). After completing dose-escalated RT, patients who received less than 6 months of chemotherapy at study entry are encouraged to receive the remaining chemotherapy to total 6 months of chemotherapy. Patients may continue chemotherapy treatment beyond 6 months at physician's discretion. Additionally, patients undergo blood sample collection, CT, MRI and tumor tissue biopsy throughout the study. After completion of study treatment, patients are followed up every 3 months for 2 years then annually for 3 years. ARM II (DOSE-ESCALATED RADIATION THERAPY): Questionnaire Administration ): Patients undergo dose-escalated RT daily, every other day, or twice weekly for 5 fractions or daily for 25 fractions (with or without concurrent fluoropyrimidine). After completing dose-escalated RT, patients who received less than 6 months of chemotherapy at study entry are encouraged to receive the remaining chemotherapy to total 6 months of chemotherapy. Patients may continue chemotherapy treatment beyond 6 months at physician's discretion. Additionally, patients undergo blood sample collection, CT, MRI and tumor tissue biopsy throughout the study. After completion of study treatment, patients are followed up every 3 months for 2 years then annually for 3 years. Arm I (standard of care) Irinotecan Hydrochloride 1: Patients continue to receive fluorouracil, irinotecan hydrochloride, leucovorin calcium, and oxaliplatin or fluorouracil, liposomal irinotecan, leucovorin calcium, and oxaliplatin or gemcitabine/nab-paclitaxel per standard of care for a total of 6 months of treatment. Patients may continue treatment beyond 6 months at physician's discretion. 2: Patients undergo standard dose radiation therapy once daily for 28 fractions and receive fluorouracil or capecitabine per SOC during radiation therapy. After completing concurrent chemoradiation, patients who received less than 6 months of chemotherapy at study entry are encouraged to receive the remaining chemotherapy to total 6 months of chemotherapy. Patients may continue chemotherapy treatment beyond 6 months at physician's discretion. 3: Patients undergo observation per standard of care. \*patients undergo blood sample collection, computed tomography (CT), magnetic resonance imaging (MRI) and tumor tissue biopsy throughout the study. Arm I (standard of care) leucovorin calcium 1: Patients continue to receive fluorouracil, irinotecan hydrochloride, leucovorin calcium, and oxaliplatin or fluorouracil, liposomal irinotecan, leucovorin calcium, and oxaliplatin or gemcitabine/nab-paclitaxel per standard of care for a total of 6 months of treatment. Patients may continue treatment beyond 6 months at physician's discretion. 2: Patients undergo standard dose radiation therapy once daily for 28 fractions and receive fluorouracil or capecitabine per SOC during radiation therapy. After completing concurrent chemoradiation, patients who received less than 6 months of chemotherapy at study entry are encouraged to receive the remaining chemotherapy to total 6 months of chemotherapy. Patients may continue chemotherapy treatment beyond 6 months at physician's discretion. 3: Patients undergo observation per standard of care. \*patients undergo blood sample collection, computed tomography (CT), magnetic resonance imaging (MRI) and tumor tissue biopsy throughout the study. Arm I (standard of care) Oxaliplatin 1: Patients continue to receive fluorouracil, irinotecan hydrochloride, leucovorin calcium, and oxaliplatin or fluorouracil, liposomal irinotecan, leucovorin calcium, and oxaliplatin or gemcitabine/nab-paclitaxel per standard of care for a total of 6 months of treatment. Patients may continue treatment beyond 6 months at physician's discretion. 2: Patients undergo standard dose radiation therapy once daily for 28 fractions and receive fluorouracil or capecitabine per SOC during radiation therapy. After completing concurrent chemoradiation, patients who received less than 6 months of chemotherapy at study entry are encouraged to receive the remaining chemotherapy to total 6 months of chemotherapy. Patients may continue chemotherapy treatment beyond 6 months at physician's discretion. 3: Patients undergo observation per standard of care. \*patients undergo blood sample collection, computed tomography (CT), magnetic resonance imaging (MRI) and tumor tissue biopsy throughout the study. Arm I (standard of care) Irinotecan Sucrosofate 1: Patients continue to receive fluorouracil, irinotecan hydrochloride, leucovorin calcium, and oxaliplatin or fluorouracil, liposomal irinotecan, leucovorin calcium, and oxaliplatin or gemcitabine/nab-paclitaxel per standard of care for a total of 6 months of treatment. Patients may continue treatment beyond 6 months at physician's discretion. 2: Patients undergo standard dose radiation therapy once daily for 28 fractions and receive fluorouracil or capecitabine per SOC during radiation therapy. After completing concurrent chemoradiation, patients who received less than 6 months of chemotherapy at study entry are encouraged to receive the remaining chemotherapy to total 6 months of chemotherapy. Patients may continue chemotherapy treatment beyond 6 months at physician's discretion. 3: Patients undergo observation per standard of care. \*patients undergo blood sample collection, computed tomography (CT), magnetic resonance imaging (MRI) and tumor tissue biopsy throughout the study. Arm I (standard of care) Gemcitabine 1: Patients continue to receive fluorouracil, irinotecan hydrochloride, leucovorin calcium, and oxaliplatin or fluorouracil, liposomal irinotecan, leucovorin calcium, and oxaliplatin or gemcitabine/nab-paclitaxel per standard of care for a total of 6 months of treatment. Patients may continue treatment beyond 6 months at physician's discretion. 2: Patients undergo standard dose radiation therapy once daily for 28 fractions and receive fluorouracil or capecitabine per SOC during radiation therapy. After completing concurrent chemoradiation, patients who received less than 6 months of chemotherapy at study entry are encouraged to receive the remaining chemotherapy to total 6 months of chemotherapy. Patients may continue chemotherapy treatment beyond 6 months at physician's discretion. 3: Patients undergo observation per standard of care. \*patients undergo blood sample collection, computed tomography (CT), magnetic resonance imaging (MRI) and tumor tissue biopsy throughout the study. Arm I (standard of care) Nab paclitaxel 1: Patients continue to receive fluorouracil, irinotecan hydrochloride, leucovorin calcium, and oxaliplatin or fluorouracil, liposomal irinotecan, leucovorin calcium, and oxaliplatin or gemcitabine/nab-paclitaxel per standard of care for a total of 6 months of treatment. Patients may continue treatment beyond 6 months at physician's discretion. 2: Patients undergo standard dose radiation therapy once daily for 28 fractions and receive fluorouracil or capecitabine per SOC during radiation therapy. After completing concurrent chemoradiation, patients who received less than 6 months of chemotherapy at study entry are encouraged to receive the remaining chemotherapy to total 6 months of chemotherapy. Patients may continue chemotherapy treatment beyond 6 months at physician's discretion. 3: Patients undergo observation per standard of care. \*patients undergo blood sample collection, computed tomography (CT), magnetic resonance imaging (MRI) and tumor tissue biopsy throughout the study. Arm I (standard of care) Radiation Therapy 1: Patients continue to receive fluorouracil, irinotecan hydrochloride, leucovorin calcium, and oxaliplatin or fluorouracil, liposomal irinotecan, leucovorin calcium, and oxaliplatin or gemcitabine/nab-paclitaxel per standard of care for a total of 6 months of treatment. Patients may continue treatment beyond 6 months at physician's discretion. 2: Patients undergo standard dose radiation therapy once daily for 28 fractions and receive fluorouracil or capecitabine per SOC during radiation therapy. After completing concurrent chemoradiation, patients who received less than 6 months of chemotherapy at study entry are encouraged to receive the remaining chemotherapy to total 6 months of chemotherapy. Patients may continue chemotherapy treatment beyond 6 months at physician's discretion. 3: Patients undergo observation per standard of care. \*patients undergo blood sample collection, computed tomography (CT), magnetic resonance imaging (MRI) and tumor tissue biopsy throughout the study. Arm I (standard of care) Capecitabine 1: Patients continue to receive fluorouracil, irinotecan hydrochloride, leucovorin calcium, and oxaliplatin or fluorouracil, liposomal irinotecan, leucovorin calcium, and oxaliplatin or gemcitabine/nab-paclitaxel per standard of care for a total of 6 months of treatment. Patients may continue treatment beyond 6 months at physician's discretion. 2: Patients undergo standard dose radiation therapy once daily for 28 fractions and receive fluorouracil or capecitabine per SOC during radiation therapy. After completing concurrent chemoradiation, patients who received less than 6 months of chemotherapy at study entry are encouraged to receive the remaining chemotherapy to total 6 months of chemotherapy. Patients may continue chemotherapy treatment beyond 6 months at physician's discretion. 3: Patients undergo observation per standard of care. \*patients undergo blood sample collection, computed tomography (CT), magnetic resonance imaging (MRI) and tumor tissue biopsy throughout the study. Arm I (standard of care) Observation Activity 1: Patients continue to receive fluorouracil, irinotecan hydrochloride, leucovorin calcium, and oxaliplatin or fluorouracil, liposomal irinotecan, leucovorin calcium, and oxaliplatin or gemcitabine/nab-paclitaxel per standard of care for a total of 6 months of treatment. Patients may continue treatment beyond 6 months at physician's discretion. 2: Patients undergo standard dose radiation therapy once daily for 28 fractions and receive fluorouracil or capecitabine per SOC during radiation therapy. After completing concurrent chemoradiation, patients who received less than 6 months of chemotherapy at study entry are encouraged to receive the remaining chemotherapy to total 6 months of chemotherapy. Patients may continue chemotherapy treatment beyond 6 months at physician's discretion. 3: Patients undergo observation per standard of care. \*patients undergo blood sample collection, computed tomography (CT), magnetic resonance imaging (MRI) and tumor tissue biopsy throughout the study. Arm I (standard of care) Biospecimen Collection 1: Patients continue to receive fluorouracil, irinotecan hydrochloride, leucovorin calcium, and oxaliplatin or fluorouracil, liposomal irinotecan, leucovorin calcium, and oxaliplatin or gemcitabine/nab-paclitaxel per standard of care for a total of 6 months of treatment. Patients may continue treatment beyond 6 months at physician's discretion. 2: Patients undergo standard dose radiation therapy once daily for 28 fractions and receive fluorouracil or capecitabine per SOC during radiation therapy. After completing concurrent chemoradiation, patients who received less than 6 months of chemotherapy at study entry are encouraged to receive the remaining chemotherapy to total 6 months of chemotherapy. Patients may continue chemotherapy treatment beyond 6 months at physician's discretion. 3: Patients undergo observation per standard of care. \*patients undergo blood sample collection, computed tomography (CT), magnetic resonance imaging (MRI) and tumor tissue biopsy throughout the study. Arm I (standard of care) Biopsy Procedure 1: Patients continue to receive fluorouracil, irinotecan hydrochloride, leucovorin calcium, and oxaliplatin or fluorouracil, liposomal irinotecan, leucovorin calcium, and oxaliplatin or gemcitabine/nab-paclitaxel per standard of care for a total of 6 months of treatment. Patients may continue treatment beyond 6 months at physician's discretion. 2: Patients undergo standard dose radiation therapy once daily for 28 fractions and receive fluorouracil or capecitabine per SOC during radiation therapy. After completing concurrent chemoradiation, patients who received less than 6 months of chemotherapy at study entry are encouraged to receive the remaining chemotherapy to total 6 months of chemotherapy. Patients may continue chemotherapy treatment beyond 6 months at physician's discretion. 3: Patients undergo observation per standard of care. \*patients undergo blood sample collection, computed tomography (CT), magnetic resonance imaging (MRI) and tumor tissue biopsy throughout the study. Arm I (standard of care) Computed Tomography 1: Patients continue to receive fluorouracil, irinotecan hydrochloride, leucovorin calcium, and oxaliplatin or fluorouracil, liposomal irinotecan, leucovorin calcium, and oxaliplatin or gemcitabine/nab-paclitaxel per standard of care for a total of 6 months of treatment. Patients may continue treatment beyond 6 months at physician's discretion. 2: Patients undergo standard dose radiation therapy once daily for 28 fractions and receive fluorouracil or capecitabine per SOC during radiation therapy. After completing concurrent chemoradiation, patients who received less than 6 months of chemotherapy at study entry are encouraged to receive the remaining chemotherapy to total 6 months of chemotherapy. Patients may continue chemotherapy treatment beyond 6 months at physician's discretion. 3: Patients undergo observation per standard of care. \*patients undergo blood sample collection, computed tomography (CT), magnetic resonance imaging (MRI) and tumor tissue biopsy throughout the study. Arm I (standard of care) Magnetic Resonance Imaging 1: Patients continue to receive fluorouracil, irinotecan hydrochloride, leucovorin calcium, and oxaliplatin or fluorouracil, liposomal irinotecan, leucovorin calcium, and oxaliplatin or gemcitabine/nab-paclitaxel per standard of care for a total of 6 months of treatment. Patients may continue treatment beyond 6 months at physician's discretion. 2: Patients undergo standard dose radiation therapy once daily for 28 fractions and receive fluorouracil or capecitabine per SOC during radiation therapy. After completing concurrent chemoradiation, patients who received less than 6 months of chemotherapy at study entry are encouraged to receive the remaining chemotherapy to total 6 months of chemotherapy. Patients may continue chemotherapy treatment beyond 6 months at physician's discretion. 3: Patients undergo observation per standard of care. \*patients undergo blood sample collection, computed tomography (CT), magnetic resonance imaging (MRI) and tumor tissue biopsy throughout the study. Arm I (standard of care) Questionnaire Administration 1: Patients continue to receive fluorouracil, irinotecan hydrochloride, leucovorin calcium, and oxaliplatin or fluorouracil, liposomal irinotecan, leucovorin calcium, and oxaliplatin or gemcitabine/nab-paclitaxel per standard of care for a total of 6 months of treatment. Patients may continue treatment beyond 6 months at physician's discretion. 2: Patients undergo standard dose radiation therapy once daily for 28 fractions and receive fluorouracil or capecitabine per SOC during radiation therapy. After completing concurrent chemoradiation, patients who received less than 6 months of chemotherapy at study entry are encouraged to receive the remaining chemotherapy to total 6 months of chemotherapy. Patients may continue chemotherapy treatment beyond 6 months at physician's discretion. 3: Patients undergo observation per standard of care. \*patients undergo blood sample collection, computed tomography (CT), magnetic resonance imaging (MRI) and tumor tissue biopsy throughout the study. ARM II (DOSE-ESCALATED RADIATION THERAPY): Dose-escalated Radiation Therapy ): Patients undergo dose-escalated RT daily, every other day, or twice weekly for 5 fractions or daily for 25 fractions (with or without concurrent fluoropyrimidine). After completing dose-escalated RT, patients who received less than 6 months of chemotherapy at study entry are encouraged to receive the remaining chemotherapy to total 6 months of chemotherapy. Patients may continue chemotherapy treatment beyond 6 months at physician's discretion. Additionally, patients undergo blood sample collection, CT, MRI and tumor tissue biopsy throughout the study. After completion of study treatment, patients are followed up every 3 months for 2 years then annually for 3 years. ARM II (DOSE-ESCALATED RADIATION THERAPY): Biospecimen Collection ): Patients undergo dose-escalated RT daily, every other day, or twice weekly for 5 fractions or daily for 25 fractions (with or without concurrent fluoropyrimidine). After completing dose-escalated RT, patients who received less than 6 months of chemotherapy at study entry are encouraged to receive the remaining chemotherapy to total 6 months of chemotherapy. Patients may continue chemotherapy treatment beyond 6 months at physician's discretion. Additionally, patients undergo blood sample collection, CT, MRI and tumor tissue biopsy throughout the study. After completion of study treatment, patients are followed up every 3 months for 2 years then annually for 3 years.
- Primary Outcome Measures
Name Time Method Overall survival (OS) assessed up to 3 years OS will be estimated by the Kaplan-Meier method (Kaplan 1958). The 3-year OS estimates between the two arms will be compared using a Z-test. A logistic regression model will be used to analyze the effects of factors, in addition to treatment, including, but not limited to the stratification factor, which may be associated with 3-year OS. The primary hypothesis of improved 3-year OS will be tested with a 1-sided significance level of 0.023.
- Secondary Outcome Measures
Name Time Method Local progression (LP) From randomization to date of failure, date of death (competing event), or last known follow-up date, assessed up to 5 years Defined as progression of the primary tumor/nodes as determined by Response Evaluation Criteria in Solid Tumors criteria. LP will be estimated by the cumulative incidence method (Kalbfleish 1980), with death as a competing risk, and compared between treatment arms using Gray's test (Gray 1988). The Fine-Gray regression model will be used to analyze the effects of factors, in addition to treatment, which may be associated with LP (Fine 1999).
Progression-free survival (PFS) From the date of randomization to the date of first PFS failure or last follow-up for patients without a reported PFS event, assessed up to 5 years Defined as local progression, distant failure, or death due to any cause. PFS will be estimated by the Kaplan-Meier method (Kaplan 1958) and estimates between treatment arms will be compared using the log-rank test (Mantel 1966). The Cox proportional hazard regression model will be used to analyze the effects of factors, in addition to treatment, which may be associated with PFS (Cox 1972).
Chemotherapy-free interval (CFI) From the date of last dose of initial chemotherapy to the date of first dose of second line chemotherapy for progression, assessed up to 5 years Defined as the time in months without chemotherapy for locally advanced pancreatic cancer post the initial chemotherapy treatment. Mean CFI will be compared between treatment arms using a Z-test. Regression modeling will be used to analyze the effects of factors, in addition to treatment, which may be associated with CFI.
Long-term radiation-related ≥ grade 3 adverse events Up to 1 year The percentage of patients on the dose-escalated radiation therapy arm will be reported
Incidence of ≥ grade 3 adverse events Up to 90 days after randomization The percentage of patients will be compared between the treatment arms using a Z-test.