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FLOT and Chemoradiation before Surgery for the Treatment of Resectable Esophageal or Gastroesophageal Junction Cancer

Trial Status: Active

This phase II trial studies how well FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) and chemoradiation before surgery work in treating patients with esophageal or gastroesophageal junction cancer that can be removed by surgery (resectable). Drugs used in chemotherapy, such as 5-fluorouracil, leucovorin, oxaliplatin, docetaxel, paclitaxel, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. FLOT and chemoradiation before surgery may be an effective treatment for patients with esophageal or gastroesophageal junction cancer.

Inclusion Criteria

  • 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
  • Have newly diagnosed, resectable cT3-T4 or node positive adenocarcinoma of the esophagus or gastroesophageal junction as assessed by computed tomography (CT) or magnetic resonance imaging (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. Eligible patients may include those with (T1-T2) node positive disease, (T3-T4) node negative or node positive disease
  • 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. Evaluation and confirmation of candidacy for each component of trimodality therapy must be documented in the chart (evaluation by medical oncologist, radiation oncologist, and surgeon)
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1
  • White blood cell (WBC) > 3 x 10^9/L
  • Hemoglobin > 9 g/dl
  • Platelets > 100 x 10^9/L
  • Total bilirubin < 1.5 x upper limit of normal
  • Aspartate aminotransferase (AST) < 3 x upper limit of normal
  • Alanine aminotransferase (ALT) < 3 x upper limit of normal
  • Serum creatinine < 1.5 x upper limit of normal (ULN) or calculated creatinine clearance > 50 mL/min (using the Cockcroft-Gault formula)
  • 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 sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. For the purpose of this study, methods that can achieve a failure rate of less than 1% per year when used consistently and correctly are considered as highly effective birth control methods and acceptable contraception. Such methods include: * Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: ** Oral ** Intravaginal ** Transdermal * Progestogen-only hormonal contraception associated with inhibition of ovulation: ** Oral ** Injectable ** Implantable * Intrauterine device (IUD) * Intrauterine hormone-releasing system (IUS) * Bilateral tubal ligation * Vasectomized partner * Sexual abstinence
  • WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements but still must undergo pregnancy testing
  • Males who are sexually active with WOCBP must agree to follow instructions for methods of contraception for the duration of the study period and for at least 3 months (duration of sperm turnover) after the last dose of chemotherapy is administered. In addition, males must be willing to refrain from sperm donation during this time. Azoospermic males are exempt from contraceptive requirements

Exclusion Criteria

  • 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, except for early stage cancers treated with curative intent, including basal or squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ of the prostate, cervix or breast
  • 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 corrected QT (QTc) > 450 msec based on electrocardiography (EKG) at screening
  • 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
  • Pregnant or breast-feeding women

Colorado

Aurora
University of Colorado Hospital
Status: ACTIVE
Contact: Jeffrey Robert Olsen
Phone: 719-365-6800
Colorado Springs
UCHealth Memorial Hospital Central
Status: ACTIVE
Contact: Jeffrey Robert Olsen
Phone: 719-365-6800
Fort Collins
Poudre Valley Hospital
Status: ACTIVE
Contact: Jeffrey Robert Olsen
Phone: 719-365-6800
Lone Tree
UCHealth Lone Tree Health Center
Status: ACTIVE
Contact: Jeffrey Robert Olsen
Phone: 719-365-6800

PRIMARY OBJECTIVE:

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

SECONDARY OBJECTIVES:

I. To evaluate safety and tolerability of the study regimen.

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

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

IV. To describe patient reported quality of life using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30), the EORTC Esophageal Cancer Module (Core Quality of Life Questionnaire Esophageal Module OES24 [QLQ-OES18]), and the National Cancer Institute (NCI) Patient Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE) measurement systems.

V. Measurement of change in the maximum standardized uptake value (SUVmax) on 18-fluoro-deoxyglucose positron emission tomography (FDG-PET) following induction FLOT, compared to initial diagnosis, and describe change in SUVmax among patients with and without a pCR to neoadjuvant therapy.

VI. Measurement of circulating tumor deoxyribonucleic acid (ctDNA) to generate initial descriptive data regarding ctDNA kinetics as a potential measure of treatment response.

OUTLINE:

INDUCTION: Patients receive fluorouracil intravenously (IV) over 24 hours, oxaliplatin IV over 2 hours, leucovorin IV over 2 hours, and docetaxel IV over 1 hour on day 1. Treatment repeats every 14 days for 3 cycles in the absence of disease progression or unacceptable toxicity.

CHEMORADIATION: Patients receive paclitaxel IV over 1 hour and carboplatin IV over 1 hour on days 1, 8, 15, 22, and 29 in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy given over 23 fractions Monday through Friday, weekly for 5 weeks in the absence of disease progression or unacceptable toxicity.

SURGERY: Patients undergo surgery.

After completion of study treatment, patients are followed up at 3, 6, 9, and 12 months.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
University of Colorado Hospital

Principal Investigator
Jeffrey Robert Olsen

  • Primary ID 19-0376
  • Secondary IDs NCI-2019-08725, 19-0376.cc
  • Clinicaltrials.gov ID NCT04028167