New chemotherapy approach for esophageal cancer before surgery

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

This study is testing a new combination of chemotherapy drugs for people with esophageal cancer to see if it can improve their chances of recovery before surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years to 100 Years
• Sex: All
• Sponsor: University of Colorado, Denver (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 7 sites (Aurora, Colorado and 6 other locations)
• Trial ID: NCT04028167 on ClinicalTrials.gov

What this trial studies

This study evaluates a novel regimen of induction chemotherapy using a combination of docetaxel, oxaliplatin, and leucovorin, along with short-term infusional 5-FU (FLOT), prior to chemoradiotherapy with concurrent carboplatin and paclitaxel. The goal is to improve clinical outcomes for patients with resectable adenocarcinoma of the esophagus or gastroesophageal junction, as current neoadjuvant treatment strategies have shown suboptimal results. Participants will receive this treatment before definitive surgical resection, aiming to enhance pathologic complete response rates and reduce disease recurrence.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-100 with newly diagnosed, resectable cT3-T4 or node-positive adenocarcinoma of the esophagus or gastroesophageal junction.

Not a fit: Patients who have previously received chemotherapy or radiation therapy for their condition may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve survival rates and reduce recurrence in patients with esophageal cancer.

How similar studies have performed: Previous studies have shown success with similar neoadjuvant chemotherapy approaches, indicating potential for this novel regimen to yield positive outcomes.

Eligibility criteria

Inclusion Criteria:

1. Provision to sign and date the consent form.
2. Stated willingness to comply with all study procedures and be available for the duration of the study.
3. Be a male or female aged 18-100.
4. 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.
5. Subjects must be previously untreated with systemic chemotherapy or radiation therapy.
6. 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.
7. ECOG performance status score of 0-1 (See Appendix).
8. Adequate bone marrow function (WBC \> 3 x 109/L; hemoglobin \> 9 g/dl; platelets \> 100 x 109/L)
9. 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)
10. 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)
11. 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.

    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
12. WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements but still must undergo pregnancy testing as described in this section.
13. 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:

1. Subjects with metastatic or inoperable esophageal or gastroesophageal junction adenocarcinoma.
2. Subjects with esophageal or gastroesophageal junction squamous cell carcinoma or adenosquamous carcinoma.
3. Prior treatment with chemotherapy or radiation therapy for esophageal or gastroesophageal adenocarcinoma.
4. 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.
5. Prior history of thoracic or abdominal radiotherapy that would overlap with the planned treatment volume.
6. Active collagen vascular disease.
7. Subjects with \> Grade 1 peripheral neuropathy.
8. 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.
9. Known history of hepatitis B or hepatitis C.
10. Clinically unstable cardiac disease including unstable angina, congestive heart failure, ventricular arrhythmia or known prior QTc \> 450msec.
11. History of allergy or hypersensitivity to any of the study drugs or study drug components.
12. 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.
13. Prisoners or subjects who are involuntarily incarcerated.
14. History of psychiatric illness that precludes completion of informed consent process, or which is deemed by the investigators as potentially influencing study compliance.
15. Known dihydropyrimidine dehydrogenase (DPD) deficiency.
16. Pregnant or breast-feeding women.

Where this trial is running

Aurora, Colorado and 6 other locations

• University of Colorado Hospital — Aurora, Colorado, United States (Recruiting)
• UCHealth Southern Colorado - Memorial Hospital Central — Colorado Springs, Colorado, United States (Recruiting)
• UCHealth Southern Colorado - Memorial Hospital North — Colorado Springs, Colorado, United States (Recruiting)
• UCHealth Northern Colorado - Poudre Valley Hospital — Fort Collins, Colorado, United States (Recruiting)
• UCHealth Northern Colorado - Harmony Campus — Fort Collins, Colorado, United States (Recruiting)
• UCHealth Northern Colorado - Greeley Hospital — Greeley, Colorado, United States (Recruiting)
• UCHealth Northern Colorado Medical Center of the Rockies — Loveland, Colorado, United States (Recruiting)

Study contacts

• Principal investigator: Jeffrey Olsen, MD — University of Colorado, Denver
• Study coordinator: McKenna Russen

Conditions Adenocarcinoma Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Resectable