Preoperative Hypofractionated Radiotherapy With FOLFOX for Esophageal or Gastroesophageal Junction Adenocarcinoma (PHOX)

Mayo Clinic

Status and phase

Enrolling

Phase 2

Conditions

Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8

Clinical Stage II Gastroesophageal Junction Adenocarcinoma AJCC v8

Clinical Stage II Esophageal Adenocarcinoma AJCC v8

Clinical Stage I Esophageal Adenocarcinoma AJCC v8

Clinical Stage I Gastroesophageal Junction Adenocarcinoma AJCC v8

Clinical Stage III Esophageal Adenocarcinoma AJCC v8

Treatments

Procedure: Biospecimen Collection

Procedure: Computed Tomography

Biological: Durvalumab

Procedure: Endoscopic Ultrasound

Drug: Fluorouracil

Drug: Docetaxel

Radiation: Hypofractionated Radiation Therapy

Drug: Leucovorin Calcium

Other: Survey Administration

Procedure: Esophagogastroduodenoscopy

Procedure: Positron Emission Tomography

Drug: Oxaliplatin

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT06078709

NCI-2023-07432 (Registry Identifier)

23-001689 (Other Identifier)

GMROR2241 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

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.

Enrollment

99 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

99 participants in 1 patient group

Treatment (FLOT and Radiation and FOLFOX)

Experimental group

Description:

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.

Treatment: