Trial Title:
Preoperative Hypofractionated Radiotherapy with FOLFOX for Esophageal or Gastroesophageal Junction Adenocarcinoma
NCT ID:
NCT06078709
Condition:
Clinical Stage I Esophageal Adenocarcinoma AJCC V8
Clinical Stage I Gastroesophageal Junction Adenocarcinoma AJCC V8
Clinical Stage II Esophageal Adenocarcinoma AJCC V8
Clinical Stage II Gastroesophageal Junction Adenocarcinoma AJCC V8
Clinical Stage III Esophageal Adenocarcinoma AJCC V8
Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC V8
Conditions: Official terms:
Adenocarcinoma
Esophageal Neoplasms
Calcium, Dietary
Leucovorin
Folic Acid
Docetaxel
Oxaliplatin
Fluorouracil
Calcium
Levoleucovorin
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Treatment (FLOT and Radiation and FOLFOX)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT and PET/CT scan
Arm group label:
Treatment (FLOT and Radiation and FOLFOX)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Other name:
Computerized Tomography (CT) scan
Intervention type:
Procedure
Intervention name:
Endoscopic Ultrasound
Description:
Undergo EUS
Arm group label:
Treatment (FLOT and Radiation and FOLFOX)
Other name:
endosonography
Other name:
EUS
Intervention type:
Procedure
Intervention name:
Esophagogastroduodenoscopy
Description:
Undergo EGD
Arm group label:
Treatment (FLOT and Radiation and FOLFOX)
Other name:
EGD
Other name:
Upper Endoscopy
Intervention type:
Drug
Intervention name:
Fluorouracil
Description:
Given IV
Arm group label:
Treatment (FLOT and Radiation and FOLFOX)
Other name:
5 Fluorouracil
Other name:
5 Fluorouracilum
Other name:
5 FU
Other name:
5-Fluoro-2,4(1H, 3H)-pyrimidinedione
Other name:
5-Fluorouracil
Other name:
5-Fluracil
Other name:
5-Fu
Other name:
5FU
Other name:
AccuSite
Other name:
Carac
Other name:
Fluoro Uracil
Other name:
Fluouracil
Other name:
Flurablastin
Other name:
Fluracedyl
Other name:
Fluracil
Other name:
Fluril
Other name:
Fluroblastin
Other name:
Ribofluor
Other name:
Ro 2-9757
Other name:
Ro-2-9757
Other name:
2,4-Dioxo-5-fluoropyrimidine
Other name:
51-21-8
Intervention type:
Radiation
Intervention name:
Hypofractionated Radiation Therapy
Description:
Undergo hypofractionated radiation therapy
Arm group label:
Treatment (FLOT and Radiation and FOLFOX)
Other name:
Hypofractionated
Other name:
Hypofractionated Radiotherapy
Other name:
hypofractionation
Other name:
Radiation, Hypofractionated
Intervention type:
Drug
Intervention name:
Leucovorin Calcium
Description:
Given IV
Arm group label:
Treatment (FLOT and Radiation and FOLFOX)
Other name:
Adinepar
Other name:
Calcifolin
Other name:
Calcium (6S)-Folinate
Other name:
Calcium Folinate
Other name:
Calcium Leucovorin
Other name:
Calfolex
Other name:
Calinat
Other name:
Cehafolin
Other name:
Citofolin
Other name:
Citrec
Other name:
Citrovorum Factor
Other name:
Cromatonbic Folinico
Other name:
Dalisol
Other name:
Disintox
Other name:
Divical
Other name:
Ecofol
Other name:
Emovis
Other name:
Factor, Citrovorum
Other name:
Flynoken A
Other name:
Folaren
Other name:
Folaxin
Other name:
FOLI-cell
Other name:
Foliben
Other name:
Folidan
Other name:
Folidar
Other name:
Folinac
Other name:
Folinate Calcium
Other name:
folinic acid
Other name:
Folinic Acid Calcium Salt Pentahydrate
Other name:
Folinoral
Other name:
Folinvit
Other name:
Foliplus
Other name:
Folix
Other name:
Imo
Other name:
Lederfolat
Other name:
Lederfolin
Other name:
Leucosar
Other name:
leucovorin
Other name:
Rescufolin
Other name:
Rescuvolin
Other name:
Tonofolin
Other name:
Wellcovorin
Intervention type:
Drug
Intervention name:
Oxaliplatin
Description:
Given IV
Arm group label:
Treatment (FLOT and Radiation and FOLFOX)
Other name:
1-OHP
Other name:
Ai Heng
Other name:
Aiheng
Other name:
Dacotin
Other name:
Dacplat
Other name:
Diaminocyclohexane Oxalatoplatinum
Other name:
Eloxatin
Other name:
Eloxatine
Other name:
JM-83
Other name:
Oxalatoplatin
Other name:
Oxalatoplatinum
Other name:
RP 54780
Other name:
RP-54780
Other name:
SR-96669
Other name:
JM83
Other name:
RP54780
Other name:
SR96669
Intervention type:
Procedure
Intervention name:
Positron Emission Tomography
Description:
Undergo PET and PET/CT scan
Arm group label:
Treatment (FLOT and Radiation and FOLFOX)
Other name:
Medical Imaging
Other name:
PET
Other name:
PET Scan
Other name:
Positron emission tomography (procedure)
Other name:
Positron Emission Tomography Scan
Other name:
Positron-Emission Tomography
Other name:
proton magnetic resonance spectroscopic imaging
Other name:
PT
Intervention type:
Other
Intervention name:
Survey Administration
Description:
Ancillary studies
Arm group label:
Treatment (FLOT and Radiation and FOLFOX)
Intervention type:
Drug
Intervention name:
Docetaxel
Description:
Given IV
Arm group label:
Treatment (FLOT and Radiation and FOLFOX)
Other name:
148408-66-6
Other name:
Docecad
Other name:
N-Debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol
Other name:
RP 56976
Other name:
RP-56976
Other name:
RP56976
Other name:
Taxotere
Summary:
This phase II trial tests how well preoperative (prior to surgery) radiation therapy with
fluorouracil, oxaliplatin, and leucovorin calcium (FOLFOX) works for the treatment of
stage I-III esophageal or gastroesophageal junction adenocarcinoma. Hypofractionated
radiation therapy delivers higher doses of radiation therapy over a shorter period of
time and may kill more tumor cells and have fewer side effects. Fluorouracil stops cells
from making deoxyribonucleic acid (DNA) and it may kill tumor cells. Leucovorin is not a
chemotherapy medication but is given in conjunction with chemotherapy. Leucovorin is used
with the chemotherapy medication fluorouracil to enhance the effects of the fluorouracil,
in other words, to make the drug work better. Oxaliplatin is in a class of medications
called platinum-containing antineoplastic agents. It damages the cell's DNA and may kill
tumor cells. Giving preoperative hypofractionated radiation with fluorouracil and
oxaliplatin may kill more tumor cells in patients with stage I-III esophageal or
gastroesophageal junction adenocarcinoma.
Detailed description:
PRIMARY OBJECTIVE:
I. To demonstrate non-inferiority of pathologic complete response (pCR) with
hypofractionated radiotherapy and concurrent FOLFOX compared to historical controls.
SECONDARY OBJECTIVES:
I. Report targeted acute grade ≥ 3 gastrointestinal (GI) toxicity, per Common Terminology
Criteria for Adverse Events (CTCAE) version (v)5.0.
II. Assess post-operative toxicity for patients undergoing esophagectomy, as determined
by the Clavien-Dindo Classification.
III. Analyze patient-reported quality of life, per Functional Assessment of Cancer
Therapy- Esophageal (FACT-E).
IV. Determine the financial toxicity of hypofractionated radiotherapy, using
Comprehensive Score for Financial Toxicity (COST-FACIT).
V. Report overall survival and progression-free survival. VI. Report long-term toxicity
secondary to trimodality therapy. VII. Report event-free survival. VIII. Assess outcomes
for patients treated with hypofractionated radiotherapy and FOLFOX but who did not
proceed to esophagectomy.
IX. Compare toxicity of chemoradiation between patients receiving proton based versus
(vs.) photon-based radiotherapy.
CORRELATIVE OBJECTIVES:
I. Explore the predictive and prognostic role for circulating tumor DNA in esophageal
cancer.
II. Study the utility of whole exome and germline sequencing to predict chemoradiation
treatment response.
III. Explore the predictive power of whole exome sequencing regarding chemoradiotherapy
toxicity.
IV. Implement whole exome and germline sequencing to personalize immunotherapy in
esophageal cancer.
V. Study the predictive and prognostic role of tumor-derived extracellular vesicles in
esophageal cancer.
OUTLINE:
INDUCTION CHEMOTHERAPY (FLOT [5-FU/leucovorin/oxaliplatin/docetaxel]): Patients receive
5-FU intravenously (IV) over 24 hours on day 1, leucovorin calcium IV over 10-120 minutes
on day 1, oxaliplatin IV over 2-6 hours on day 1, and docetaxel IV over 1 hour on day 1
of each cycle. Treatment repeats every 2 weeks for a total of up to 4 cycles in the
absence of disease progression or unacceptable toxicity. After completion of FLOT,
patients undergo radiation therapy daily for 3 weeks with 2 concurrent cycles of FOLFOX.
FOLFOX: Patients receive oxaliplatin IV over 2-6 hours on day 1, leucovorin calcium IV
over 10-120 minutes on day 1, and and fluorouracil IV over 46-48 hours on days 1 and 2.
of each cycle. Treatment repeats every 2 weeks for a total of 3 cycles in the absence of
disease progression or unacceptable toxicity. Starting at cycle 2, patients undergo
radiation therapy daily on Monday through Friday for a total of 15 treatments. Patients
undergo esophagogastroduodenoscopy (EGD) and/or endoscopic ultrasound (EUS) during
screening and undergo computed tomography (CT)/position emission tomography (PET) scan
and CT scan as well as blood and tissue sample collection throughout the study.
After completion of study treatment, patients are followed up at 6,12 and 24 months and
then up to 5 years.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Age ≥ 18 years
- Histological confirmation of esophageal or gastroesophageal junction adenocarcinoma,
American Joint Committee on Cancer (AJCC) 8th edition stage T1-4N0-3M0
- Candidate for trimodality therapy: neoadjuvant chemotherapy, chemoradiation, and
esophagectomy
- Surgical consultation has confirmed that patient is an appropriate candidate for
esophagectomy
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
- Negative pregnancy test done ≤ 7 days prior to chemotherapy, for women of
childbearing potential only
- Ability to provide written informed consent and complete questionnaire(s) by
themselves or with assistance
- Willing to return to enrolling institution for follow-up (during the active
monitoring phase of the study)
- Willing to provide blood and tissue samples for correlative research purposes
Exclusion Criteria:
- Clinical or biopsy-proven distant metastatic disease (AJCC 8th edition stage
TanyNanyM1)
- Cervical or upper esophageal tumor
- Prior chemotherapy or radiotherapy for esophageal cancer or history of radiotherapy
to the thorax
- Co-morbid systemic illnesses or other severe concurrent disease which, in the
judgement of the investigator, would make the patient inappropriate for entry into
this study or interfere significantly with proper assessment of adverse events
- Receiving any investigational agent which would be considered as a treatment for the
primary neoplasm or other active malignancy ≤ 1 year prior to registration that is
considered by the investigator to interfere with the current treatment or
measurement of outcomes
- Any of the following:
- Pregnant women
- Nursing women
- Men or women of childbearing potential who are unwilling to employ adequate
contraception
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Mayo Clinic in Arizona
Address:
City:
Scottsdale
Zip:
85259
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Clinical Trials Referral Office
Phone:
855-776-0015
Email:
mayocliniccancerstudies@mayo.edu
Contact backup:
Last name:
Jonathan B. Ashman, MD, PhD
Facility:
Name:
Mayo Clinic in Florida
Address:
City:
Jacksonville
Zip:
32224-9980
Country:
United States
Status:
Recruiting
Contact:
Last name:
Clinical Trials Referral Office
Phone:
855-776-0015
Email:
mayocliniccancerstudies@mayo.edu
Contact backup:
Last name:
Michael S. Rutenberg, MD, PhD
Facility:
Name:
Mayo Clinic in Rochester
Address:
City:
Rochester
Zip:
55905
Country:
United States
Status:
Recruiting
Contact:
Last name:
Clinical Trials Referral Office
Phone:
855-776-0015
Email:
mayocliniccancerstudies@mayo.edu
Contact backup:
Last name:
Christopher L. Hallemeier, MD
Start date:
November 20, 2023
Completion date:
November 30, 2026
Lead sponsor:
Agency:
Mayo Clinic
Agency class:
Other
Source:
Mayo Clinic
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06078709
https://www.mayo.edu/research/clinical-trials
