Radiotherapy + Chemotherapy for Esophageal Cancer

(PHOX Trial)

Recruiting in Palo Alto (17 mi)

+2 other locations

Overseen by Christopher L. Hallemeier, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Mayo Clinic

Disqualifiers: Metastatic disease, Upper esophageal tumor, Prior chemotherapy, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the treatment Radiotherapy + Chemotherapy for Esophageal Cancer?

Research shows that 5-Fluorouracil (5-FU) combined with radiotherapy has been used to improve tumor control in esophageal cancer, and the combination of 5-FU and cisplatin is commonly used for this condition. Additionally, fluorinated pyrimidines, like 5-FU, are known to enhance the effects of radiotherapy, making them effective in treating esophageal cancer. ^{1 2 3 4 5}

Is the combination of radiotherapy and chemotherapy safe for esophageal cancer?

The combination of oxaliplatin, 5-fluorouracil, and leucovorin with radiotherapy has been shown to be safe for treating locally advanced esophageal cancer. Another study found that using docetaxel and 5-fluorouracil with radiotherapy was also safe, with mild blood-related side effects and some cases of esophagitis (inflammation of the esophagus). ^{6 7 8 9 10}

How is the treatment of Radiotherapy + Chemotherapy for Esophageal Cancer unique?

This treatment combines oxaliplatin, 5-fluorouracil, and leucovorin with hypofractionated radiotherapy, which is a novel approach compared to the more common use of cisplatin with 5-fluorouracil. The use of oxaliplatin and hypofractionated radiotherapy may offer a different safety and efficacy profile for patients with locally advanced esophageal cancer. ^{2 3 4 6 7}

Eligibility Criteria

This trial is for adults with stage I-III esophageal or gastroesophageal junction adenocarcinoma confirmed by biopsy, who are fit for surgery and have not had prior chemo or radiotherapy to the chest. Participants must be able to consent, complete questionnaires, provide blood samples for research, and use effective contraception if of childbearing potential.

Inclusion Criteria

I am 18 years old or older.

You are willing to donate blood samples for correlative research.

My cancer is confirmed as esophageal or gastroesophageal junction adenocarcinoma, at a specific stage.

Exclusion Criteria

I am currently breastfeeding.

My cancer is located in my cervix or upper esophagus.

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

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Induction Chemotherapy

Patients receive FLOT (5-FU/leucovorin/oxaliplatin/docetaxel) every 2 weeks for up to 4 cycles

8 weeks

4 visits (in-person)

Radiation and Concurrent Chemotherapy

Patients undergo radiation therapy daily for 3 weeks with 2 concurrent cycles of FOLFOX

6 weeks

15 visits (in-person) for radiation, 3 visits (in-person) for chemotherapy

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Follow-up at 6, 12, and 24 months, then annually up to 5 years

Treatment Details

Interventions

• Fluorouracil (Chemotherapy)
• Hypofractionated Radiation Therapy (Radiation Therapy)
• Leucovorin Calcium (Chemotherapy)
• Oxaliplatin (Chemotherapy)

Trial Overview The study tests preoperative hypofractionated radiation therapy combined with FOLFOX (fluorouracil, oxaliplatin, leucovorin calcium) in treating esophageal cancer. The goal is to see if this approach kills more tumor cells before surgery compared to standard treatments.

Participant Groups

Group I: Treatment (FLOT and Radiation and FOLFOX) Experimental Treatment 11 Interventions

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.

Fluorouracil is already approved in United States, European Union, Canada for the following indications:

🇺🇸 Approved in United States as 5-Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer
• Skin cancer

🇪🇺 Approved in European Union as 5-Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer

🇨🇦 Approved in Canada as 5-Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Mayo Clinic in Florida Jacksonville, FL

Mayo Clinic in Arizona Scottsdale, AZ

Mayo Clinic in Rochester Rochester, MN

Who Is Running the Clinical Trial?

Mayo Clinic Lead Sponsor

National Cancer Institute (NCI) Collaborator

References

1. United States pubmed.ncbi.nlm.nih.gov

Phase I trial of Orzel (UFT plus leucovorin), cisplatin, and radiotherapy in the treatment of potentially resectable esophageal cancer. [2013] Fluorinated pyrimidines have been established as radiosensitizers in the combined modality therapy of esophageal cancer. UFT, an oral combination of a 5-fluorouracil pro-drug (uracil) and a dihydropyrimidine dehydrogenase inhibitor (ftorafur), may provide improvement in the ease of administration with equal efficacy. This Phase I study was designed to determine the maximal tolerated dose and dose-limiting toxicity of UFT, leucovorin, and cisplatin when given with radiotherapy in the neoadjuvant treatment of resectable esophageal cancer.

2. Greece pubmed.ncbi.nlm.nih.gov

Gene expression changes in a chemoresistant model with human esophageal cancer xenografts using cDNA microarray. [2015] 5-Fluorouracil (5-FU) and cisplatin combined chemotherapy (FP) is commonly used for esophageal cancer. Acquired resistance needs to be overcome to improve the chemotherapeutic effect.

3. United States pubmed.ncbi.nlm.nih.gov

Evaluation of multimodality treatment of locoregional esophageal carcinoma by Southwest Oncology Group 9060. [2013] Continuous infusion 5-fluorouracil (CI5-FU) has been utilized concurrently with radiotherapy to improve tumor control. In this pilot trial, cisplatin, CI5FU, and radiotherapy were utilized for the treatment of locoregional esophageal carcinoma. It was postulated that the combination would be well tolerated and associated with high response rate and survival duration.

4. United States pubmed.ncbi.nlm.nih.gov

Does paclitaxel improve the chemoradiotherapy of locoregionally advanced esophageal cancer? A nonrandomized comparison with fluorouracil-based therapy. [2022] A phase II trial of accelerated fractionation radiation with concurrent cisplatin and paclitaxel chemotherapy was performed to investigate the role of the paclitaxel, when substituted for fluorouracil (5-FU), in the chemoradiotherapy of esophageal cancer.

5. Italy pubmed.ncbi.nlm.nih.gov

Preoperative low-dose weekly cisplatin and continuous infusion fluorouracil plus hyperfractionated radiotherapy in stage II-III esophageal carcinoma. [2019] The optimal regimen of preoperative chemoradiotherapy for resectable esophageal cancer has not been established. We evaluated accelerated hyperfractionated radiotherapy (RT) concurrent to low-dose weekly cisplatin and continuous infusion fluorouracil (LDCI-FU) followed by esophagectomy in patients with locally advanced squamous cell carcinoma (SCC) of the esophagus.

6. China pubmed.ncbi.nlm.nih.gov

A phase I dose escalation study of S-1 with concurrent radiotherapy in elderly patients with esophageal cancer. [2022] Concurrent chemoradiotherapy (CRT) with 5-fluorouracil (5-FU) and cisplatin (CDDP) are often associated with significant incidence of toxic effects in elderly patients with esophageal cancer. This phase I trial was designed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of S-1, an oral 5-FU derivative, when given with radiotherapy in elderly patients.

7. United States pubmed.ncbi.nlm.nih.gov

Concurrent oxaliplatin, 5-fluorouracil, and radiotherapy in the treatment of locally advanced esophageal carcinoma. [2018] The combination of oxaliplatin, 5-fluorouracil, and leucovorin with concurrent radiotherapy was demonstrated to be a safe regimen for locally advanced esophageal carcinoma in a prior phase I study. We now report the efficacy data for 42 patients treated with this regimen.

8. United States pubmed.ncbi.nlm.nih.gov

Role of definitive chemoradiotherapy using docetaxel and 5-fluorouracil in patients with unresectable locally advanced esophageal squamous cell carcinoma: a phase II study. [2022] Definitive chemoradiotherapy (CRT) with docetaxel (DOC) and 5-fluorouracil (5-FU) is a unique regimen for esophageal cancer. In this prospective phase II study, antitumor effect and safety of CRT using DOC and 5-FU for inoperable locally advanced esophageal cancer were evaluated. DOC 7.5 mg/m2 was infused on days 1, 8, 22, and 29. 5-FU 250 mg/m2 /day was infused continuously on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-45. Radiotherapy was given to 66 Gy in 33 fractions. Eleven patients with thoracic and five with cervical esophageal cancer were eligible. All patients had esophageal squamous cell carcinoma (ESCC). The response rate was 94%, with complete response in five patients (31%) and partial response in 10 (63%). Hematologic toxicity was mild; only one patient (6%) had Grade 1 leukopenia. Nonhematologic Grade 3 or higher adverse events were esophagitis (31%), anorexia (6%), and esophago-bronchial fistula (6%). No treatment-related deaths occurred. The median time to progression was 20 months and overall 3-year and 5-year survival were 44% and 31%, respectively. Definitive CRT using DOC and 5-FU could be performed safely, and it demonstrated a favorable antitumor effect for ESCC. This regimen might be indicated in patients in whom it is desirable to avoid myelosuppression and progression of renal impairment.

9. United States pubmed.ncbi.nlm.nih.gov

Definitive chemoradiation therapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-R) in advanced esophageal cancer: a phase 2 trial (KDOG 0501-P2). [2022] A previous phase 1 study suggested that definitive chemoradiation therapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-R) is tolerable and active in patients with advanced esophageal cancer (AEC). This phase 2 study was designed to confirm the efficacy and toxicity of DCF-R in AEC.

10. United States pubmed.ncbi.nlm.nih.gov

A phase II study of S-1 with concurrent radiotherapy in elderly patients with esophageal cancer. [2022] Concurrent chemoradiotherapy (CCRT) using conventional platinum-based doublets are often associated with significant incidence of toxic effects in elderly patients with esophageal cancer. We previously reported a phase I trial of CCRT using S-1, an oral 5-fluorouracil derivative, which yielded well safe and active outcomes.