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Radiothérapie hypofractionnée préopératoire avec FOLFOX pour l'adénocarcinome de la jonction œsophagienne ou gastro-œsophagienne (PHOX)

29 septembre 2026 mis à jour par: Mayo Clinic

Radiothérapie hypofractionnée préopératoire avec FOLFOX pour l'adénocarcinome de la jonction œsophagienne/gastro-œsophagienne (PHOX)

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.

Aperçu de l'étude

Statut

Recrutement

Les conditions

Intervention / Traitement

Description détaillée

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.

X. Compare clinical outcomes and pCR for patients receiving hypofractioned radiotherapy but different induction chemo (immuno) therapy regimens: no induction vs. fluorouracil, oxaliplatin, leucovorin, docetaxel (FLOT) vs. FLOT + durvalumab.

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: 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 6 cycles in the absence of disease progression or unacceptable toxicity. Eligible patients also receive durvalumab IV over 1 hour every 4 weeks 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.

Type d'étude

Interventionnel

Inscription (Estimé)

99

Phase

  • Phase 2

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Coordonnées de l'étude

Lieux d'étude

  • États-Unis
    • Arizona
      • Scottsdale, Arizona, États-Unis, 85259
        • Pas encore de recrutement
        • Mayo Clinic in Arizona
        • Contact:
        • Chercheur principal:
          • Jonathan B. Ashman, MD, PhD
    • Florida
      • Jacksonville, Florida, États-Unis, 32224-9980
        • Actif, ne recrute pas
        • Mayo Clinic in Florida
    • Minnesota
      • Rochester, Minnesota, États-Unis, 55905
        • Recrutement
        • Mayo Clinic in Rochester
        • Contact:
        • Chercheur principal:
          • Christopher L. Hallemeier, MD

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans et plus (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

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 chemo (immuno) therapy, 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

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: N / A
  • Modèle interventionnel: Affectation à un seul groupe
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: Treatment (FLOT and Radiation and FOLFOX)

Patients received Induction Chemotherapy [FLOT (5-FU/leucovorin/oxaliplatin/docetaxel)] following by radiation therapy daily for 3 weeks with 2 concurrent cycles of FOLFOX per protocol. See detailed description for more information.
Médicament: Docetaxel

Given IV

Autres noms:
  • Taxotère
  • Docécad
  • RP56976
  • RP 56976
  • RP-56976
  • 148408-66-6
  • N-débenzoyl-N-(tert-butoxycarbonyl)-10-désacétyltaxol
Médicament: Fluorouracil

Given IV

Autres noms:
  • 5-Fluracil
  • Fluracil
  • 5 Fluorouracile
  • 5 Fluorouracilum
  • 5 UF
  • 5-Fluoro-2,4(1H, 3H)-pyrimidinedione
  • 5-Fluorouracile
  • 5-Fu
  • 5FU
  • AccuSite
  • Carac
  • Uracile fluoré
  • Fluouracil
  • Flurablastine
  • Fluracédyl
  • Flurill
  • Fluroblastine
  • Ribofluor
  • Ro 2-9757
  • Ro-2-9757
  • 2,4-dioxo-5-fluoropyrimidine
  • 51-21-8
Procédure: Biospecimen Collection

Undergo blood sample collection

Autres noms:
  • Collecte d'échantillons biologiques
  • Spécimen biologique collecté
  • Collecte de spécimens
Médicament: Leucovorin Calcium

Given IV

Autres noms:
  • Wellcovorine
  • acide folinique
  • Adinépar
  • Calcifoline
  • Calcium (6S)-Folinate
  • Folinate de Calcium
  • Leucovorine calcique
  • Calfolex
  • Calinat
  • Céhafoline
  • Citofolin
  • Citrec
  • Facteur Citrovore
  • Cromatonbic Folinico
  • Dalisol
  • Désintox
  • Divical
  • Écofol
  • Émovis
  • Facteur, Citrovorum
  • Flynoken A
  • Folarène
  • Folaxine
  • Cellule FOLI
  • Foliben
  • Folidan
  • Folidar
  • Folinac
  • Pentahydrate de sel de calcium d'acide folinique
  • Folinoral
  • Folinvit
  • Foliplus
  • Folix
  • Imo
  • Lederfolat
  • Léderfoline
  • Leucosar
  • la leucovorine
  • Réscufoline
  • Rescuvoline
  • Tonofoline
Médicament: Oxaliplatin

Given IV

Autres noms:
  • 1-OHP
  • Dacotine
  • Dacplat
  • Eloxatine
  • Ai Heng
  • Aiheng
  • Diaminocyclohexane Oxalatoplatine
  • JM-83
  • Oxalatoplatine
  • RP 54780
  • RP-54780
  • SR-96669
  • SR96669
  • JM83
  • RP54780
Radiation: Hypofractionated Radiation Therapy

Undergo hypofractionated radiation therapy

Autres noms:
  • Radiothérapie hypofractionnée
  • hypofractionnement
  • Radiation, hypofractionné
  • Hypofractionné
Autre: Survey Administration

Ancillary studies

Biologique: Durvalumab

Given IV

Autres noms:
  • Imfinzi
  • MEDI-4736
  • MEDI4736
  • MÉDI 4736
  • Immunoglobuline G1
  • Anti-(Protéine humaine B7-H1) (Chaîne lourde monoclonale humaine MEDI4736)
  • Disulfure avec chaîne Kappa monoclonale humaine MEDI4736
Procédure: Esophagogastroduodenoscopy

Undergo EGD

Autres noms:
  • EGD
  • Endoscopie supérieure
Procédure: Computed Tomography

Undergo CT and PET/CT scan

Autres noms:
  • TDM
  • CHAT
  • Scanner
  • Tomographie axiale informatisée
  • Tomographie assistée par ordinateur
  • Tomodensitométrie
  • tomographie
  • Tomographie axiale informatisée (procédure)
  • Tomodensitométrie (TDM)
Procédure: Endoscopic Ultrasound

Undergo EUS

Autres noms:
  • endosonographie
  • EUS
Procédure: Positron Emission Tomography

Undergo PET and PET/CT scan

Autres noms:
  • ANIMAUX
  • TEP-scan
  • Scan de tomographie par émission de positrons
  • Tomographie par émission de positrons
  • imagerie spectroscopique par résonance magnétique du proton
  • PT
  • L'imagerie médicale
  • Tomographie par émission de positrons (procédure)

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Pathologic complete response
Délai: Up to 5 years after completion of chemoradiation

A single-group design will be used to test whether the proportion is potentially non-inferior, with a non-inferiority proportion (P0) of 0.13 (H0: P ≤ 0.13 versus H1: P > 0.13).
Up to 5 years after completion of chemoradiation

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Incidence of acute ≥ gastrointestinal (GI) adverse events (AEs)
Délai: Up to 6 weeks after completion of chemoradiation

Report acute grade ≥ 3 GI AEs per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 criteria. Will be summarized descriptively.
Up to 6 weeks after completion of chemoradiation
Incidence of post operative AEs
Délai: From surgery up to 6 months after completion of chemoradiation

Determined by the Clavien-Dindo Classification. Will be summarized descriptively.
From surgery up to 6 months after completion of chemoradiation
Patient-reported quality of life (QOL)
Délai: Up to 24 months after completion of chemoradiation

Per Functional Assessment of Cancer Therapy- Esophageal. Will be assessed over time. Wilcoxon signed-rank tests will be used to calculate p-values. Descriptive statistics and graphical methods will also be used to summarize the data.
Up to 24 months after completion of chemoradiation
Financial toxicity
Délai: Up to 24 months after completion of chemoradiation

Financial toxicity will be measured using the COmprehensive Score for financial Toxicity (COST), a patient-reported outcome measure that describes the financial distress experienced by cancer patients. The survey consists of 12 questions, each answered with a 0-4 scale where 0=Not at all, 1=A little bit, 2=Somewhat, 3=Quite a bit, and 4=Very much. Results will be reported descriptively and include separate consideration of individual item scores.
Up to 24 months after completion of chemoradiation
Overall survival (OS)
Délai: From study entry to death from any cause, up to 5 years after completion of chemoradiation

Will be assessed graphically using the Kaplan-Meier method. Summary statistics will be reported, including medians, 95% confidence intervals, etc.
From study entry to death from any cause, up to 5 years after completion of chemoradiation
Progression-free survival (PFS)
Délai: From study entry to the first of either disease progression or death, up to 5 years after completion chemoradiation

Will be assessed graphically using the Kaplan-Meier method. Summary statistics will be reported, including medians, 95% confidence intervals, etc.
From study entry to the first of either disease progression or death, up to 5 years after completion chemoradiation
Long-term toxicity secondary to trimodality therapy
Délai: Up to 5 years after completion of chemoradiation

Will be reported descriptively using CTCAE version 5.0 criteria.
Up to 5 years after completion of chemoradiation
Event free survival
Délai: From study entry to the first of either disease progression or recurrence or relapse or death, up to 5 years after completion of chemoradiation

Will be assessed graphically using the Kaplan-Meier method. Summary statistics will be reported, including medians, 95% confidence intervals, etc.
From study entry to the first of either disease progression or recurrence or relapse or death, up to 5 years after completion of chemoradiation
Outcomes for patients treated with hypofractionated radiotherapy and FOLFOX but who did not proceed to esophagectomy
Délai: Up to 5 years after completion of chemoradiation

OS and PFS will be assess using Kaplan-Meier methodology. Summary statistics will be reported, including medians, 95% confidence intervals, etc. AEs and QOL data will be reported with summary statistics and graphical methods, as appropriate.
Up to 5 years after completion of chemoradiation
Toxicity of chemoradiation between patients receiving proton based versus photon-based radiotherapy
Délai: Up to 5 years after completion of chemoradiation

Will be done descriptively, reporting frequencies and percentages between patients.
Up to 5 years after completion of chemoradiation
Toxicity of chemoradiation between groups receiving proton based versus photon-based radiotherapy
Délai: Up to 5 years after completion of chemoradiation

Will be done descriptively, reporting toxicity rates between groups using the chi-square test.
Up to 5 years after completion of chemoradiation

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Mayo Clinic

Les enquêteurs

  • Chercheur principal: Christopher L. Hallemeier, MD, Mayo Clinic in Rochester

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Liens utiles

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

21 novembre 2023

Achèvement primaire (Estimé)

25 mai 2029

Achèvement de l'étude (Estimé)

25 mai 2029

Dates d'inscription aux études

Première soumission

3 octobre 2023

Première soumission répondant aux critères de contrôle qualité

9 octobre 2023

Première publication (Réel)

12 octobre 2023

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

1 octobre 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

29 septembre 2026

Dernière vérification

1 septembre 2026

Plus d'information

Termes liés à cette étude

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • GMROR2241
  • 23-001689 (Autre identifiant: Mayo Clinic Institutional Review Board)
  • NCI-2023-07432 (Identificateur de registre: CTRP (Clinical Trial Reporting Program))
  • GMROR2241 (Autre identifiant: Mayo Clinic Radiation Oncology)

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Oui

Étudie un produit d'appareil réglementé par la FDA américaine

Non

produit fabriqué et exporté des États-Unis.

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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