Induction Chemotherapy for Esophageal Cancer

Overseen By Tanya Smith, BS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Rochester

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

40 Participants Needed

Trial Summary

What is the purpose of this trial?

Evaluate mFOLFOX6 (5-Fluorouracil, Leucovorin and Oxaliplatin) chemotherapy as induction treatment prior to standard neoadjuvant chemoradiation to decrease the rate of distant recurrence among patients with locally advanced esophageal cancer.

Will I have to stop taking my current medications?

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

What data supports the effectiveness of the drug combination of 5-Fluorouracil, Leucovorin, and Oxaliplatin for esophageal cancer?

Research shows that the combination of 5-Fluorouracil, Leucovorin, and Oxaliplatin (FOLFOX) is effective as an adjuvant therapy for esophageal squamous cell carcinoma, with improved outcomes compared to surgery or radiation alone. Additionally, a study found that a similar regimen led to a complete response in 80% of patients, suggesting its potential effectiveness. ^{1 2 3 4 5}

Is induction chemotherapy for esophageal cancer safe?

Studies have shown that the combination of oxaliplatin, 5-fluorouracil, and leucovorin, sometimes with radiotherapy, is generally safe for treating esophageal cancer, though there can be side effects like febrile neutropenia (fever with low white blood cell count) and other blood-related issues. ^{1 6 7 8 9}

How is the drug 5-Fluorouracil, Leucovorin, Oxaliplatin unique for treating esophageal cancer?

This drug combination is unique because it includes oxaliplatin, which is not commonly used in standard treatments for esophageal cancer, and it may offer a different mechanism of action compared to the more traditional use of cisplatin with 5-fluorouracil. This could potentially provide an alternative for patients who have developed resistance to the usual chemotherapy regimens. ^{2 3 10 11 12}

Research Team

Richard Dunne, MD

Principal Investigator

University of Rochester Wilmot Cancer Center

Eligibility Criteria

This trial is for adults with locally advanced esophageal cancer that can potentially be removed by surgery. They must have good organ function, no prior treatments for esophageal cancer, not be pregnant or planning to become pregnant, and have no serious non-cancer illnesses or neuropathy.

Inclusion Criteria

My blood tests show my organs are functioning well.

My disease can possibly be removed with surgery.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

I have moderate to severe nerve damage.

I've been cancer-free for over 5 years or had certain skin or in situ cancers treated effectively.

I do not have any chronic diseases that would interfere with the study's treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Chemotherapy

Participants receive 3 cycles of mFOLFOX6 chemotherapy

6 weeks

3 visits (in-person)

Chemoradiation

Participants undergo standard chemoradiation therapy

5 cycles

Surgery

Participants undergo surgery following chemoradiation

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

• 5-Fluorouracil
• Leucovorin
• Oxaliplatin

Trial Overview The study tests if adding mFOLFOX6 chemotherapy before the usual chemoradiation treatment improves outcomes in patients with advanced esophageal cancer. It aims to reduce the chance of the cancer spreading elsewhere in the body.

Participant Groups

Group I: Induction Chemotherapy /Chemoradiation Experimental Treatment 2 Interventions

mFOLFOX6 for 3 cycles - Oxaliplatin 85 mg/m2, 5-fluorouracil 2400mg/m2/46 hours, 5-fluorouracil bolus 400mg/m2 and leucovorin 400 mg/m2, then chemoradiation for 5 cycles - Carboplatin AUC 2mg/mL/min, Paclitaxel 50 mg/m2 and radiation therapy.

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

Approved in European Union as 5-FU for:

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

Approved in United States as 5-FU for:

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

Approved in Canada as 5-FU for:

• Colorectal cancer
• Breast cancer
• Stomach cancer

Approved in Japan as 5-FU for:

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

Who Is Running the Clinical Trial?

University of Rochester

Lead Sponsor

Trials

883

Recruited

555,000+

Findings from Research

The study established a 5-Fluorouracil (5-FU) and cisplatin-resistant xenograft model in SCID mice to investigate the mechanisms behind acquired resistance in esophageal cancer treatment.

Gene expression analysis revealed that resistance to FP chemotherapy is linked to the activation of specific genes related to 5-FU and cisplatin, as well as the PI3K/AKT signaling pathway, suggesting potential targets for overcoming resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene expression changes in a chemoresistant model with human esophageal cancer xenografts using cDNA microarray. Yoshida, T., Miyoshi, T., Seike, J., et al.[2015]

In a phase II study involving 50 patients with advanced oesophageal cancer, the addition of cetuximab to the standard treatment of 5-FU/cisplatin/docetaxel (TPF) and chemoradiotherapy resulted in a clinical complete response (cCR) rate of 12% and an overall response rate of 54%.

The median overall survival for patients who underwent complete surgical resection was significantly longer at 42.1 months compared to 24.9 months for those who did not have surgery, indicating that achieving a complete resection is crucial for improving survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II Study Evaluating Combined Neoadjuvant Cetuximab and Chemotherapy Followed by Chemoradiotherapy and Concomitant Cetuximab in Locoregional Oesophageal Cancer Patients. Alsina, M., Rivera, F., Ramos, FJ., et al.[2019]

In a study of 92 patients with esophageal cancer treated with the DCF chemotherapy regimen, the use of pegfilgrastim significantly reduced the incidence of febrile neutropenia from 32.2% to 3.0%, highlighting its efficacy as a primary prophylaxis.

Patients receiving pegfilgrastim also experienced fewer severe adverse effects (12.1% vs 69.5%) and had a lower rate of treatment interruptions, indicating that pegfilgrastim not only enhances safety but also supports the continuation of effective cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk factors for febrile neutropenia and effectiveness of primary prophylaxis with pegfilgrastim in patients with esophageal cancer treated with docetaxel, cisplatin, and 5-fluorouracil. Ohkura, Y., Ueno, M., Udagawa, H.[2020]

In a phase 2 study involving 42 patients with advanced esophageal cancer, the combination of docetaxel, cisplatin, and 5-fluorouracil (DCF-R) showed a clinical complete response rate of 52.4%, indicating significant efficacy in treating this condition.

While DCF-R was effective, it also led to considerable side effects, including high rates of leukopenia and neutropenia, suggesting that while the treatment is promising, careful monitoring for these toxicities is necessary.

NCBI (Pubmed)

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). Higuchi, K., Komori, S., Tanabe, S., et al.[2022]

The combination of oxaliplatin, 5-fluorouracil, and leucovorin with concurrent radiotherapy was found to be safe and effective for treating locally advanced esophageal carcinoma, with 42 patients showing promising results in a structured treatment regimen.

Patients who received preoperative concurrent chemoradiotherapy had a median survival of 28 months, with significant down-staging observed in 16 out of 24 patients, indicating the potential for improved outcomes with this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent oxaliplatin, 5-fluorouracil, and radiotherapy in the treatment of locally advanced esophageal carcinoma. O'Connor, BM., Chadha, MK., Pande, A., et al.[2018]

References

1. Korea (South) pubmed.ncbi.nlm.nih.gov

A Randomized Phase II Study of Leucovorin/5-Fluorouracil with or without Oxaliplatin (LV5FU2 vs. FOLFOX) for Curatively-Resected, Node-Positive Esophageal Squamous Cell Carcinoma. [2018]

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

Gene expression changes in a chemoresistant model with human esophageal cancer xenografts using cDNA microarray. [2015]

3. England pubmed.ncbi.nlm.nih.gov

Combined intensive chemoradiotherapy for organ preservation in patients with resectable and non-resectable oesophageal cancer. [2019]

4. France pubmed.ncbi.nlm.nih.gov

A phase II Study Evaluating Combined Neoadjuvant Cetuximab and Chemotherapy Followed by Chemoradiotherapy and Concomitant Cetuximab in Locoregional Oesophageal Cancer Patients. [2019]

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

Efficacy of cisplatin, 5-fluorouracil, and paclitaxel regimen for carcinoma of the esophagus. [2015]

6. England pubmed.ncbi.nlm.nih.gov

Risk factors for febrile neutropenia and effectiveness of primary prophylaxis with pegfilgrastim in patients with esophageal cancer treated with docetaxel, cisplatin, and 5-fluorouracil. [2020]

7. 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]

8. Germany pubmed.ncbi.nlm.nih.gov

A phase II study of oxaliplatin in combination with leucovorin and fluorouracil as first-line chemotherapy in patients with metastatic squamous cell carcinoma of esophagus. [2018]

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

Concurrent oxaliplatin, 5-fluorouracil, and radiotherapy in the treatment of locally advanced esophageal carcinoma. [2018]

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

A 3-Year Overall Survival Update From a Phase 2 Study of Chemoselection With DCF and Subsequent Conversion Surgery for Locally Advanced Unresectable Esophageal Cancer. [2020]

11. Greece pubmed.ncbi.nlm.nih.gov

Docetaxel plus 5-fluorouracil and cisplatin (DCF) induction chemotherapy for locally advanced borderline-resectable T4 esophageal cancer. [2022]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Pre-operative induction chemotherapy for small cell carcinoma of the oesophagus: a case report. [2019]