A Phase III Randomized Trial of Dose Escalated Radiation in Locally Advanced Pancreas Cancer (LAPC) Patients (LAP100)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- NRG Oncology
- 入组人数
- 356
- 试验地点
- 427
- 主要终点
- Overall survival (OS)
研究概览
简要总结
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 4-8 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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •At time of enrollment, the patient must have received 4-8 months of active chemotherapy with FOLFIRINOX or NALIRIFOX or gemcitabine/nab-paclitaxel. Patients are permitted to receive more than 1 type of chemotherapy for reasons other than radiographic progression by Response Evaluation Criteria in Solid Tumors (RECIST) (i.e. chemotherapy regimen switch is allowed for toxicity, and/or switch is allowed for toxicity and/or CA19-9 level not declining). Patients are allowed to receive chemotherapy after restaging scans, as long as 1) restaging scans are performed after at least 4 months of chemotherapy and 2) the total chemotherapy duration does not exceed 8 months
- •"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 pre-study entry chemotherapy
- •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, CT chest/CT pelvis/MRI abdomen, or PET/CT performed prior to enrollment
- •Age ≥ 18 years
- •Performance status Eastern Cooperative Oncology Group (ECOG) 0-2
- •Required initial laboratory values:
- •All laboratory values must be obtained any time prior to initiation of chemotherapy up to 30 days post initiation of chemotherapy
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x upper limit of normal (ULN)
- •BASELINE CA19-9 AND BILIRUBIN REQUIREMENTS: The purpose is to obtain a baseline CA19-9 in the setting of a normal (or close to normal) bilirubin, since serologic response by serial CA19-9 measurements is part of post-chemotherapy eligibility criteria
- •If baseline CA19-9 > 37 U/mL the concurrent bilirubin must be ≤ 1.5 x ULN. (Note: if the bilirubin is not ≤ 1.5 x ULN both the CA19-9 and concurrent bilirubin can be repeated until bilirubin is ≤ 1.5 x ULN, as long as done within specified timeframe [up to 30 days post chemotherapy initiation])
- •If baseline CA19-9 U/mL ≤ 37, there are no restrictions on the required concurrent bilirubin level, and this can be the accepted baseline value
- •Prior radiation treatment
- •Has the patient had prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
- •Prior non-overlapping radiation (e.g., breast, head and neck, extremity) is permitted
- •If uncertain about prior overlap, please contact the study principal investigator, Dr. Nina Sanford
- •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 200 u/mL OR a 70% decline from pre-chemotherapy level (i.e. a patient with post induction chemotherapy CA199 value ≥ 200 u/mL would qualify, as long as they had at least 70% drop from baseline CA199 value; similarly, a patient with less than a 70% decline would qualify as long as absolute value post induction chemotherapy is under 200 u/mL) (must be completed any time post month 4 of chemotherapy and prior to study entry)
- •If baseline CA19-9 is not elevated (defined as ≤ 37 u/mL) the post-pre-entry chemotherapy CA19-9 must remain ≤ 37 u/mL (must be completed any time post month 4 of chemotherapy and prior to study entry)
- •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, or PET/CT 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
排除标准
- 未提供
研究组 & 干预措施
Arm II (dose-escalated RT)
Patients undergo dose-escalated RT daily, every other day, or twice weekly for 5 fractions or daily for 25 fractions (with or without concurrent fluorouracil or capecitabine for 25 fractions only). The 5-fraction regimen is preferred when feasible. 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. Patients may optionally undergo PET/CT prior to treatment.
干预措施: Computed Tomography (Procedure)
Arm II (dose-escalated RT)
Patients undergo dose-escalated RT daily, every other day, or twice weekly for 5 fractions or daily for 25 fractions (with or without concurrent fluorouracil or capecitabine for 25 fractions only). The 5-fraction regimen is preferred when feasible. 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. Patients may optionally undergo PET/CT prior to treatment.
干预措施: Questionnaire Administration (Other)
Arm II (dose-escalated RT)
Patients undergo dose-escalated RT daily, every other day, or twice weekly for 5 fractions or daily for 25 fractions (with or without concurrent fluorouracil or capecitabine for 25 fractions only). The 5-fraction regimen is preferred when feasible. 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. Patients may optionally undergo PET/CT prior to treatment.
干预措施: Positron Emission Tomography (Procedure)
Arm I (Options 1, 2, or 3)
See Detailed Description.
干预措施: Oxaliplatin (Drug)
Arm II (dose-escalated RT)
Patients undergo dose-escalated RT daily, every other day, or twice weekly for 5 fractions or daily for 25 fractions (with or without concurrent fluorouracil or capecitabine for 25 fractions only). The 5-fraction regimen is preferred when feasible. 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. Patients may optionally undergo PET/CT prior to treatment.
干预措施: Fluorouracil (Drug)
Arm I (Options 1, 2, or 3)
See Detailed Description.
干预措施: Biopsy Procedure (Procedure)
Arm I (Options 1, 2, or 3)
See Detailed Description.
干预措施: Biospecimen Collection (Procedure)
Arm I (Options 1, 2, or 3)
See Detailed Description.
干预措施: Irinotecan Sucrosofate (Drug)
Arm I (Options 1, 2, or 3)
See Detailed Description.
干预措施: Computed Tomography (Procedure)
Arm I (Options 1, 2, or 3)
See Detailed Description.
干预措施: Positron Emission Tomography (Procedure)
Arm II (dose-escalated RT)
Patients undergo dose-escalated RT daily, every other day, or twice weekly for 5 fractions or daily for 25 fractions (with or without concurrent fluorouracil or capecitabine for 25 fractions only). The 5-fraction regimen is preferred when feasible. 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. Patients may optionally undergo PET/CT prior to treatment.
干预措施: Dose-escalated Radiation Therapy (Radiation)
Arm I (Options 1, 2, or 3)
See Detailed Description.
干预措施: Nab-paclitaxel (Drug)
Arm I (Options 1, 2, or 3)
See Detailed Description.
干预措施: Irinotecan Hydrochloride (Drug)
Arm I (Options 1, 2, or 3)
See Detailed Description.
干预措施: Capecitabine (Drug)
Arm II (dose-escalated RT)
Patients undergo dose-escalated RT daily, every other day, or twice weekly for 5 fractions or daily for 25 fractions (with or without concurrent fluorouracil or capecitabine for 25 fractions only). The 5-fraction regimen is preferred when feasible. 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. Patients may optionally undergo PET/CT prior to treatment.
干预措施: Biopsy Procedure (Procedure)
Arm II (dose-escalated RT)
Patients undergo dose-escalated RT daily, every other day, or twice weekly for 5 fractions or daily for 25 fractions (with or without concurrent fluorouracil or capecitabine for 25 fractions only). The 5-fraction regimen is preferred when feasible. 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. Patients may optionally undergo PET/CT prior to treatment.
干预措施: Capecitabine (Drug)
Arm II (dose-escalated RT)
Patients undergo dose-escalated RT daily, every other day, or twice weekly for 5 fractions or daily for 25 fractions (with or without concurrent fluorouracil or capecitabine for 25 fractions only). The 5-fraction regimen is preferred when feasible. 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. Patients may optionally undergo PET/CT prior to treatment.
干预措施: Biospecimen Collection (Procedure)
Arm I (Options 1, 2, or 3)
See Detailed Description.
干预措施: Fluorouracil (Drug)
Arm I (Options 1, 2, or 3)
See Detailed Description.
干预措施: Magnetic Resonance Imaging (Procedure)
Arm I (Options 1, 2, or 3)
See Detailed Description.
干预措施: Observation Activity (Other)
Arm I (Options 1, 2, or 3)
See Detailed Description.
干预措施: Questionnaire Administration (Other)
Arm I (Options 1, 2, or 3)
See Detailed Description.
干预措施: Radiation Therapy (Radiation)
Arm II (dose-escalated RT)
Patients undergo dose-escalated RT daily, every other day, or twice weekly for 5 fractions or daily for 25 fractions (with or without concurrent fluorouracil or capecitabine for 25 fractions only). The 5-fraction regimen is preferred when feasible. 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. Patients may optionally undergo PET/CT prior to treatment.
干预措施: Magnetic Resonance Imaging (Procedure)
Arm I (Options 1, 2, or 3)
See Detailed Description.
干预措施: Gemcitabine (Drug)
Arm I (Options 1, 2, or 3)
See Detailed Description.
干预措施: Leucovorin Calcium (Drug)
结局指标
主要结局
Overall survival (OS)
时间窗: From randomization to the date of death or last follow-up, 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 (level based on not having stopped at either of the 2 planned interim analyses).
次要结局
- Incidence of ≥ grade 3 adverse events(Up to 90 days after randomization)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- Long-term radiation-related ≥ grade 3 adverse events(Up to 1 year after randomization)
- Incidence of ≥ grade 3 adverse events(Up to 90 days after randomization)