Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Induction FLOT With CROSS CRT for Esophageal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04028167
Recruitment Status : Recruiting
First Posted : July 22, 2019
Last Update Posted : February 21, 2021
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Colorado, Denver

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

Condition or disease Intervention/treatment Phase
Adenocarcinoma Esophagus Adenocarcinoma of the Gastroesophageal Junction Drug: Sequential FLOT followed by chemoradiation Phase 2

Detailed Description:

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Induction FLOT Followed by Neoadjuvant Chemoradiation in Patients With Resectable Adenocarcinoma of the Esophagus or Gastroesophageal Junction
Actual Study Start Date : February 11, 2020
Estimated Primary Completion Date : April 19, 2024
Estimated Study Completion Date : April 2025


Arm Intervention/treatment
Experimental: Sequential FLOT followed by chemoradiation
Sequential Chemotherapy with Docetaxel, Oxaliplatin, and 5-Fluorouracil/Leucovorin followed by chemoradiation with concurrent carboplatin and paclitaxel
Drug: Sequential FLOT followed by chemoradiation
Chemotherapy with Docetaxel, Oxaliplatin, and 5-Fluorouracil/ Leucovorin




Primary Outcome Measures :
  1. Evaluate the rate of pathologic complete response (pCR) to the study regimen. [ Time Frame: 5 years ]
    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


Secondary Outcome Measures :
  1. To determine estimates of the 1-year overall survival and disease-free survival among patients treated with the study regimen. [ Time Frame: 5 years ]
    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

  2. To describe toxicity of the study regimen as a component of neoadjuvant therapy for the study population. [ Time Frame: 5 years ]
    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.

  3. Patient reported quality of life [ Time Frame: 5 years ]
    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)

  4. 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. [ Time Frame: 5 years ]
    Percentage reduction in SUVmax from the baseline to the post-chemotherapy PET.

  5. Measurement of ctDNA to generate initial descriptive data regarding ctDNA kinetics as a potential measure of treatment response [ Time Frame: 5 years ]
    The sensitivity and specificity of detectable ctDNA postoperatively to predict 1 year disease-free survival within the study cohort.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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, 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.
  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04028167


Contacts
Layout table for location contacts
Contact: Robyn Swing 719-365-6665 robyn.swing@ucdenver.edu
Contact: Emily Berens 720-848-8031 emily.berens@ucdenver.edu

Locations
Layout table for location information
United States, Colorado
UCHealth Memorial Hospital South Recruiting
Colorado Springs, Colorado, United States, 80909
Contact: Angie Valdez, BS    719-365-6665      
UCHealth Memorial Hospital North Recruiting
Colorado Springs, Colorado, United States, 80920
Contact: Sarah Tarver    719-364-0058    sarah.tarver@uchealth.org   
UCH Lone Tree Recruiting
Lone Tree, Colorado, United States, 80124
Contact: Lisa Lopez       lisa.lopez@ucdenver.edu   
Sponsors and Collaborators
University of Colorado, Denver
National Cancer Institute (NCI)
Layout table for additonal information
Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT04028167    
Other Study ID Numbers: 19-0376.cc
P30CA046934 ( U.S. NIH Grant/Contract )
First Posted: July 22, 2019    Key Record Dates
Last Update Posted: February 21, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by University of Colorado, Denver:
Resectable
Additional relevant MeSH terms:
Layout table for MeSH terms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms