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Adenocarcinoma EsophagusPhase 2NCT04028167

Induction FLOT With CROSS CRT for Esophageal Cancer

A Phase 2 study testing Sequential FLOT followed by chemoradiation in people with Adenocarcinoma Esophagus and Adenocarcinoma of the Gastroesophageal Junction, run by University of Colorado, Denver at 7 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 100 years
What is being tested?
Sequential FLOT followed by chemoradiation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
7 sitesUnited States
Study dates
8 Apr 2020to 19 Apr 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 100 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.
  • 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 as described in this section.
  • 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.

Who cannot join

  • 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.
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  • 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.
  • Pregnant or breast-feeding women.

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

United States7 sites

  • University of Colorado Hospital

    Aurora, Colorado, 80045

  • UCHealth Southern Colorado - Memorial Hospital Central

    Colorado Springs, Colorado, 80909

  • UCHealth Southern Colorado - Memorial Hospital North

    Colorado Springs, Colorado, 80920

  • UCHealth Northern Colorado - Poudre Valley Hospital

    Fort Collins, Colorado, 80524

  • UCHealth Northern Colorado - Harmony Campus

    Fort Collins, Colorado, 80528

  • UCHealth Northern Colorado - Greeley Hospital

    Greeley, Colorado, 80634

  • UCHealth Northern Colorado Medical Center of the Rockies

    Loveland, Colorado, 80538

Other trials in United States

About this study

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

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

Read the 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.

Being tested
Sequential FLOT followed by chemoradiation
Keywords
Resectable
Medical subject headings
Adenocarcinoma Of Esophagus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Sequential FLOT followed by chemoradiationDrug

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

Study groups in NCT04028167
Study groupRoleWhat they receive
Sequential FLOT followed by chemoradiationExperimentalSequential Chemotherapy with Docetaxel, Oxaliplatin, and 5-Fluorouracil/Leucovorin followed by chemoradiation with concurrent carboplatin and paclitaxel
Receives: Drug: Sequential FLOT followed by chemoradiation

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 5 years

Secondary outcomes (5)

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

    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

    Measured: 5 years

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

    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.

    Measured: 5 years

  3. Patient reported quality of life

    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)

    Measured: 5 years

  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.

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

    Measured: 5 years

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

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

    Measured: 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Jul 2019
  2. Study start8 Apr 2020
  3. Primary completion2 Jan 2026
  4. Study completion19 Apr 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
40 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04028167
Sponsor's protocol ID
19-0376.cc
Other IDs
P30CA046934
Status last verified
Jan 2026
First submitted
4 Jun 2019
Last updated
9 Jan 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Sequential FLOT followed by chemoradiation in people with Adenocarcinoma Esophagus and Adenocarcinoma of the Gastroesophageal Junction, run by University of Colorado, Denver at 7 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 32 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 9 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Evaluate the rate of pathologic complete response (pCR) to the study regimen. (time frame: 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04028167.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2026.

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