Clinical trial NCT06078709: Preoperative Hypofractionated Radiotherapy With FOLFOX for Esophageal or Gastroesophageal Junction Adenocarcinoma
Official title: Preoperative Hypofractionated Radiotherapy With FOLFOX for Esophageal/Gastroesophageal Junction Adenocarcinoma (PHOX)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: 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
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2023-10-12
Enrollment: 99
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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

Primary outcomes:
measure: Pathologic complete response
timeFrame: Up to 5 years after completion of chemoradiation
Secondary outcomes:
measure: Incidence of acute ≥ gastrointestinal (GI) adverse events (AEs)
timeFrame: Up to 6 weeks after completion of chemoradiation
measure: Incidence of post operative AEs
timeFrame: From surgery up to 6 months after completion of chemoradiation
measure: Patient-reported quality of life (QOL)
timeFrame: Up to 24 months after completion of chemoradiation
measure: Financial toxicity
timeFrame: Up to 24 months after completion of chemoradiation
measure: Overall survival (OS)
timeFrame: From study entry to death from any cause, up to 5 years after completion of chemoradiation
measure: Progression-free survival (PFS)
timeFrame: From study entry to the first of either disease progression or death, up to 5 years after completion chemoradiation
measure: Long-term toxicity secondary to trimodality therapy
timeFrame: Up to 5 years after completion of chemoradiation
measure: Event free survival
timeFrame: From study entry to the first of either disease progression or recurrence or relapse or death, up to 5 years after completion of chemoradiation
measure: Outcomes for patients treated with hypofractionated radiotherapy and FOLFOX but who did not proceed to esophagectomy
timeFrame: Up to 5 years after completion of chemoradiation
measure: Toxicity of chemoradiation between patients receiving proton based versus photon-based radiotherapy
timeFrame: Up to 5 years after completion of chemoradiation
measure: Toxicity of chemoradiation between groups receiving proton based versus photon-based radiotherapy
timeFrame: Up to 5 years after completion of chemoradiation
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic in Arizona
state: Arizona
city: Jacksonville
country: United States
facility: Mayo Clinic in Florida
state: Florida
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
Study officials:
affiliation: Mayo Clinic in Rochester
name: Christopher L. Hallemeier, MD
role: PRINCIPAL_INVESTIGATOR
References: