Induction FLOT With CROSS CRT for Esophageal Cancer

NCT04028167 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 19-0376.ccP30CA046934
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 7

Brief Summary

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

Conditions

Adenocarcinoma Esophagus; Adenocarcinoma of the Gastroesophageal Junction

Keywords

Resectable

Outcome Measures

Primary Outcomes (1)

• Evaluate the rate of pathologic complete response (pCR) to the study regimen.

  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

  5 years

Secondary Outcomes (5)

• To determine estimates of the 1-year overall survival and disease-free survival among patients treated with the study regimen.

  5 years

• To describe toxicity of the study regimen as a component of neoadjuvant therapy for the study population.

  5 years

• Patient reported quality of life

  5 years

• Measurement of change in the SUVmax on FDG-PET following induction FLOT, compared to initial diagnosis, and describe change in SUVmax among patients with and without a pCR to neoadjuvant therapy.

  5 years

• Measurement of ctDNA to generate initial descriptive data regarding ctDNA kinetics as a potential measure of treatment response

  5 years

Study Arms (1)

Sequential FLOT followed by chemoradiation

EXPERIMENTAL

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

Drug: Sequential FLOT followed by chemoradiation

Interventions

Sequential FLOT followed by chemoradiation DRUG

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

Sequential FLOT followed by chemoradiation

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision to sign and date the consent form.
• Stated willingness to comply with all study procedures and be available for the duration of the study.
• Be a male or female aged 18-100.
• Have newly diagnosed, resectable cT3-T4 or node positive adenocarcinoma of the esophagus or gastroesophageal junction as assessed by CT or MRI of the chest, abdomen and pelvis and by endoscopic ultrasound, with pathologic diagnosis obtained within 3 months of signing consent, without delivery of prior chemotherapy or radiation therapy.
• Subjects must be previously untreated with systemic chemotherapy or radiation therapy.
• Subjects must be deemed a candidate for trimodality therapy (radiation, chemotherapy and surgery) based upon multidisciplinary evaluation with plan for preoperative chemoradiation followed by surgical resection.
• ECOG performance status score of 0-1 (See Appendix).
• Adequate bone marrow function (WBC \> 3 x 109/L; hemoglobin \> 9 g/dl; platelets \> 100 x 109/L)
• Adequate liver function (total bilirubin \< 1.5 x upper limit of normal, AST \< 3 x upper limit of normal, and ALT \< 3 x upper limit of normal)
• Serum creatinine \< 1.5 x ULN or calculated creatinine clearance \> 50 mL/min (using the Cockcroft-Gault formula)
• Males:
• Creatinine CL (mL/min) = Weight (kg) x (140 - Age) 72 x serum creatinine (mg/dL)
• Females:
• Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 72 x serum creatinine (mg/dL)
• Women of child-bearing potential (WOCBP) must have a negative serum or urine pregnancy test within 2 weeks prior to study enrollment and must agree to follow instructions for method(s) of contraception for the duration of the study period and at least 3 months after the last dose of chemotherapy is administered. For the purpose of this study, a woman is considered of childbearing potential following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy.

You may not qualify if:

• Subjects with metastatic or inoperable esophageal or gastroesophageal junction adenocarcinoma.
• Subjects with esophageal or gastroesophageal junction squamous cell carcinoma or adenosquamous carcinoma.
• Prior treatment with chemotherapy or radiation therapy for esophageal or gastroesophageal adenocarcinoma.
• Prior malignancy active within the previous 3 years that is felt to exclude the patient from definitive therapy of esophageal or gastroesophageal cancer, or if prior cancer therapy is felt by the investigator to significantly increase toxicity risk from the study regimen.
• Prior history of thoracic or abdominal radiotherapy that would overlap with the planned treatment volume.
• Active collagen vascular disease.
• Subjects with \> Grade 1 peripheral neuropathy.
• Any serious or uncontrolled medical disorder or active infection, that in the opinion of the investigator may increase the risk associated with study participation, study treatment administration or would impair the ability of the subject to receive study treatment.
• Known history of hepatitis B or hepatitis C.
• Clinically unstable cardiac disease including unstable angina, congestive heart failure, ventricular arrhythmia or known prior QTc \> 450msec.
• History of allergy or hypersensitivity to any of the study drugs or study drug components.
• Any contraindications to any of the study drugs of the chemotherapy regimens (FLOT or carboplatin/paclitaxel) selected by the investigator. Investigators should refer to the local package insert of the chemotherapy drugs.
• Prisoners or subjects who are involuntarily incarcerated.
• History of psychiatric illness that precludes completion of informed consent process, or which is deemed by the investigators as potentially influencing study compliance.
• Known dihydropyrimidine dehydrogenase (DPD) deficiency.

Sponsors & Collaborators

• University of Colorado, Denver: lead
• American Cancer Society, Inc.: collaborator
• Cancer League of Colorado: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (7)

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

UCHealth Southern Colorado - Memorial Hospital Central

Colorado Springs, Colorado, 80909, United States

Location

UCHealth Southern Colorado - Memorial Hospital North

Colorado Springs, Colorado, 80920, United States

Location

UCHealth Northern Colorado - Poudre Valley Hospital

Fort Collins, Colorado, 80524, United States

Location

UCHealth Northern Colorado - Harmony Campus

Fort Collins, Colorado, 80528, United States

Location

UCHealth Northern Colorado - Greeley Hospital

Greeley, Colorado, 80634, United States

Location

UCHealth Northern Colorado Medical Center of the Rockies

Loveland, Colorado, 80538, United States

Location

MeSH Terms

Conditions

Adenocarcinoma Of Esophagus

Study Officials

• Jeffrey Olsen, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2019
• First Posted: July 22, 2019
• Study Start: April 8, 2020
• Primary Completion: January 2, 2026
• Study Completion (Estimated): April 19, 2027
• Last Updated: January 9, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)