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Esophageal Cancer

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Paclitaxel

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Sequential Chemotherapy with Docetaxel, Oxaliplatin, and 5-Fluorouracil/Leucovorin followed by chemoradiation with concurrent carboplatin and paclitaxel

Chemotherapy with Docetaxel, Oxaliplatin, and 5-Fluorouracil/ Leucovorin

Sequential FLOT followed by chemoradiation

McKenna Russen

Amanda Emery

Lisa Deschaine

Lea Rodningen@uchelath.org

Lisa Lopez

Jeffrey Olsen

This study evaluates a novel regimen of induction chemotherapy using a combination of docetaxel, oxaliplatin, and leucovorin, with short term infusional 5-FU (FLOT), given prior to chemoradiotherapy with concurrent carboplatin and paclitaxel, as neoadjuvant therapy prior to definitive surgical resection for patients with adenocarcinoma of the esophagus or gastroesophageal junction

Clinical outcomes following standard of care therapy for resectable esophageal and gastroesophageal junction adenocarcinoma are suboptimal, with low rates of pathologic complete response (pCR) to current neoadjuvant treatment strategies. Although significant progress has been made by incorporation of neoadjuvant chemoradiation or perioperative chemotherapy, most patients will ultimately develop disease recurrence, with both locoregional and distant recurrence representing a significant component of failure. For patients receiving preoperative chemoradiation, a regimen consisting of concurrent carboplatin and paclitaxel with radiotherapy has been established as a standard of care based on the Chemoradiotherapy for Esophageal Cancer Followed by Surgery Study (CROSS). In the long term results of CROSS, locoregional progression was noted in 22% of patients receiving neoadjuvant therapy, with distant progression in 39%.

Recent studies have also suggested perioperative chemotherapy as a potential alternative strategy for selected patients, based on results of the MAGIC trial, which included a subset patients with esophageal/GE junction tumor location, and demonstrated improved survival for patients receiving perioperative epirubicin, cisplatin, and infusional 5-fluorouracil (ECF) compared to surgery alone. The FLOT4-AIO trial has subsequently demonstrated a further overall survival benefit to a perioperative regimen of docetaxel, oxaliplatin, and leucovorin, with short term infusional 5-FU (FLOT) compared to ECF. A regimen of perioperative FLOT is currently being compared to preoperative chemoradiotherapy using the CROSS regimen in the ongoing ESOPEC trial (NCT02509286).

Given the significant risk of recurrence either with the CROSS preoperative chemoradiation regimen, or the perioperative FLOT regimen, it is plausible that selected patients may benefit from a combination of intensified systemic therapy using the FLOT backbone, in combination with sequential preoperative chemoradiation due to the known risk of locoregional recurrence in this population. This study evaluates the proposed neoadjuvant regimen of induction FLOT followed by neoadjuvant chemoradiation in patients with resectable cT3/T4 or node positive adenocarcinoma of the esophagus or gastroesophageal junction.

Induction FLOT With CROSS CRT for Esophageal Cancer

Phase II Study of Induction FLOT Followed by Neoadjuvant Chemoradiation in Patients With Resectable Adenocarcinoma of the Esophagus or Gastroesophageal Junction

The percentage of pathologic complete response at resection for patients who has completed the study regimen of induction FLOT, CROSS regimen chemoradiation, and surgical resection

The endpoint of overall survival will be defined by the proportion of evaluable patients that are living at a 1-year time interval from initial pathologic diagnosis. The endpoint of disease-free survival will be defined by the proportion of evaluable patients that are living and free of cancer recurrence at a 1-year time interval from initial pathologic diagnosis

The proportion of patients experiencing any ≥grade 3 and ≥grade 4 toxicity as defined by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be recorded.

Patient reported quality of life outcomes using the validated European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30)

Percentage reduction in SUVmax from the baseline to the post-chemotherapy PET.

The sensitivity and specificity of detectable ctDNA postoperatively to predict 1 year disease-free survival within the study cohort.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Induction FLOT With CROSS CRT for Esophageal Cancer	NCT04028167	Adenocarcinoma ... Adenocarcinoma ...	Sequential FLOT...	18 Years - 100 Years	University of Colorado, Denver
Induction FLOT With CROSS CRT for Esophageal Cancer	NCT04028167	Adenocarcinoma ... Adenocarcinoma ...	Sequential FLOT...	18 Years - 100 Years	University of Colorado, Denver
Induction FLOT With CROSS CRT for Esophageal Cancer	NCT04028167	Adenocarcinoma ... Adenocarcinoma ...	Sequential FLOT...	18 Years - 100 Years	University of Colorado, Denver

Spots Global Cancer Trial Database for sequential flot followed by chemoradiation