Preoperative Hypofractionated Radiotherapy With FOLFOX for Esophageal/Gastroesophageal Junction Adenocarcinoma (PHOX)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- Mayo Clinic
- 入组人数
- 99
- 试验地点
- 6
- 主要终点
- Pathologic complete response
研究概览
简要总结
This phase II trial tests how well preoperative (prior to surgery) radiation therapy with fluorouracil, oxaliplatin, and leucovorin calcium (FOLFOX) works for the treatment of stage I-III esophageal or gastroesophageal junction adenocarcinoma. 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. Fluorouracil stops cells from making deoxyribonucleic acid (DNA) and it may kill tumor cells. Leucovorin is not a chemotherapy medication but is given in conjunction with chemotherapy. Leucovorin is used with the chemotherapy medication fluorouracil to enhance the effects of the fluorouracil, in other words, to make the drug work better. Oxaliplatin is in a class of medications called platinum-containing antineoplastic agents. It damages the cell's DNA and may kill tumor cells. Giving preoperative hypofractionated radiation with fluorouracil and oxaliplatin may kill more tumor cells in patients with stage I-III esophageal or gastroesophageal junction adenocarcinoma.
详细描述
PRIMARY OBJECTIVE:
I. To demonstrate non-inferiority of pathologic complete response (pCR) with hypofractionated radiotherapy and concurrent FOLFOX compared to historical controls.
SECONDARY OBJECTIVES:
I. Report targeted acute grade ≥ 3 gastrointestinal (GI) toxicity, per Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0.
II. Assess post-operative toxicity for patients undergoing esophagectomy, as determined by the Clavien-Dindo Classification.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Age ≥ 18 years
- •Histological confirmation of esophageal or gastroesophageal junction adenocarcinoma, American Joint Committee on Cancer (AJCC) 8th edition stage T1-4N0-3M0
- •Candidate for trimodality therapy: neoadjuvant chemo (immuno) therapy, chemoradiation, and esophagectomy
- •Surgical consultation has confirmed that patient is an appropriate candidate for esophagectomy
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
- •Negative pregnancy test done ≤ 7 days prior to chemotherapy, for women of childbearing potential only
- •Ability to provide written informed consent and complete questionnaire(s) by themselves or with assistance
- •Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
- •Willing to provide blood and tissue samples for correlative research purposes
排除标准
- •Clinical or biopsy-proven distant metastatic disease (AJCC 8th edition stage TanyNanyM1)
- •Cervical or upper esophageal tumor
- •Prior chemotherapy or radiotherapy for esophageal cancer or history of radiotherapy to the thorax
- •Co-morbid systemic illnesses or other severe concurrent disease which, in the judgement of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with proper assessment of adverse events
- •Receiving any investigational agent which would be considered as a treatment for the primary neoplasm or other active malignancy ≤ 1 year prior to registration that is considered by the investigator to interfere with the current treatment or measurement of outcomes
- •Any of the following:
- •Pregnant women
- •Nursing women
- •Men or women of childbearing potential who are unwilling to employ adequate contraception
研究组 & 干预措施
Treatment (FLOT and Radiation and FOLFOX)
Patients received Induction Chemotherapy [FLOT (5-FU/leucovorin/oxaliplatin/docetaxel)] following by radiation therapy daily for 3 weeks with 2 concurrent cycles of FOLFOX per protocol. See detailed description for more information.
干预措施: Biospecimen Collection (Procedure)
Treatment (FLOT and Radiation and FOLFOX)
Patients received Induction Chemotherapy [FLOT (5-FU/leucovorin/oxaliplatin/docetaxel)] following by radiation therapy daily for 3 weeks with 2 concurrent cycles of FOLFOX per protocol. See detailed description for more information.
干预措施: Fluorouracil (Drug)
Treatment (FLOT and Radiation and FOLFOX)
Patients received Induction Chemotherapy [FLOT (5-FU/leucovorin/oxaliplatin/docetaxel)] following by radiation therapy daily for 3 weeks with 2 concurrent cycles of FOLFOX per protocol. See detailed description for more information.
干预措施: Leucovorin Calcium (Drug)
Treatment (FLOT and Radiation and FOLFOX)
Patients received Induction Chemotherapy [FLOT (5-FU/leucovorin/oxaliplatin/docetaxel)] following by radiation therapy daily for 3 weeks with 2 concurrent cycles of FOLFOX per protocol. See detailed description for more information.
干预措施: Oxaliplatin (Drug)
Treatment (FLOT and Radiation and FOLFOX)
Patients received Induction Chemotherapy [FLOT (5-FU/leucovorin/oxaliplatin/docetaxel)] following by radiation therapy daily for 3 weeks with 2 concurrent cycles of FOLFOX per protocol. See detailed description for more information.
干预措施: Docetaxel (Drug)
Treatment (FLOT and Radiation and FOLFOX)
Patients received Induction Chemotherapy [FLOT (5-FU/leucovorin/oxaliplatin/docetaxel)] following by radiation therapy daily for 3 weeks with 2 concurrent cycles of FOLFOX per protocol. See detailed description for more information.
干预措施: Durvalumab (Biological)
Treatment (FLOT and Radiation and FOLFOX)
Patients received Induction Chemotherapy [FLOT (5-FU/leucovorin/oxaliplatin/docetaxel)] following by radiation therapy daily for 3 weeks with 2 concurrent cycles of FOLFOX per protocol. See detailed description for more information.
干预措施: Computed Tomography (Procedure)
Treatment (FLOT and Radiation and FOLFOX)
Patients received Induction Chemotherapy [FLOT (5-FU/leucovorin/oxaliplatin/docetaxel)] following by radiation therapy daily for 3 weeks with 2 concurrent cycles of FOLFOX per protocol. See detailed description for more information.
干预措施: Endoscopic Ultrasound (Procedure)
Treatment (FLOT and Radiation and FOLFOX)
Patients received Induction Chemotherapy [FLOT (5-FU/leucovorin/oxaliplatin/docetaxel)] following by radiation therapy daily for 3 weeks with 2 concurrent cycles of FOLFOX per protocol. See detailed description for more information.
干预措施: Esophagogastroduodenoscopy (Procedure)
Treatment (FLOT and Radiation and FOLFOX)
Patients received Induction Chemotherapy [FLOT (5-FU/leucovorin/oxaliplatin/docetaxel)] following by radiation therapy daily for 3 weeks with 2 concurrent cycles of FOLFOX per protocol. See detailed description for more information.
干预措施: Hypofractionated Radiation Therapy (Radiation)
Treatment (FLOT and Radiation and FOLFOX)
Patients received Induction Chemotherapy [FLOT (5-FU/leucovorin/oxaliplatin/docetaxel)] following by radiation therapy daily for 3 weeks with 2 concurrent cycles of FOLFOX per protocol. See detailed description for more information.
干预措施: Positron Emission Tomography (Procedure)
Treatment (FLOT and Radiation and FOLFOX)
Patients received Induction Chemotherapy [FLOT (5-FU/leucovorin/oxaliplatin/docetaxel)] following by radiation therapy daily for 3 weeks with 2 concurrent cycles of FOLFOX per protocol. See detailed description for more information.
干预措施: Survey Administration (Other)
结局指标
主要结局
Pathologic complete response
时间窗: Up to 5 years after completion of chemoradiation
A single-group design will be used to test whether the proportion is potentially non-inferior, with a non-inferiority proportion (P0) of 0.13 (H0: P ≤ 0.13 versus H1: P \> 0.13).
次要结局
- Incidence of acute ≥ gastrointestinal (GI) adverse events (AEs)(Up to 6 weeks after completion of chemoradiation)
- Progression-free survival (PFS)(From study entry to the first of either disease progression or death, up to 5 years after completion chemoradiation)
- Long-term toxicity secondary to trimodality therapy(Up to 5 years after completion of chemoradiation)
- Event free survival(From study entry to the first of either disease progression or recurrence or relapse or death, up to 5 years after completion of chemoradiation)
- Outcomes for patients treated with hypofractionated radiotherapy and FOLFOX but who did not proceed to esophagectomy(Up to 5 years after completion of chemoradiation)
- Toxicity of chemoradiation between groups receiving proton based versus photon-based radiotherapy(Up to 5 years after completion of chemoradiation)
- Incidence of post operative AEs(From surgery up to 6 months after completion of chemoradiation)
- Patient-reported quality of life (QOL)(Up to 24 months after completion of chemoradiation)
- Financial toxicity(Up to 24 months after completion of chemoradiation)
- Overall survival (OS)(From study entry to death from any cause, up to 5 years after completion of chemoradiation)
- Toxicity of chemoradiation between patients receiving proton based versus photon-based radiotherapy(Up to 5 years after completion of chemoradiation)