Induction Chemotherapy for Esophageal Cancer

Overseen By Tanya Smith, BS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Rochester

Disqualifiers: Prior chemotherapy, Distant metastases, Neuropathy, others

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a chemotherapy mix called mFOLFOX6 (which includes 5-Fluorouracil, Leucovorin, and Oxaliplatin) can reduce the recurrence of esophageal cancer when administered before the usual chemoradiation treatment. The goal is to determine if this approach can better control the cancer and prevent its spread. It targets individuals diagnosed with advanced esophageal cancer that might be operable. Participants should have no prior treatments, such as chemotherapy or surgery, for their esophageal tumor and must agree to use contraception if they are of reproductive age. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in cancer care.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that the mFOLFOX6 treatment, which includes the drugs 5-Fluorouracil, Leucovorin, and Oxaliplatin, is generally safe for patients with esophageal cancer. Studies have found that this treatment is effective and has fewer serious side effects compared to stronger chemotherapy options. Specifically, it often results in fewer severe side effects, such as grade 3 or 4 toxicities, which are more intense and potentially harmful.

In simpler terms, while every treatment can have side effects, mFOLFOX6 appears easier for patients to handle than some other chemotherapy combinations. This makes it a promising choice for those considering participation in a clinical trial for esophageal cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for esophageal cancer?

Researchers are excited about this treatment for esophageal cancer because it combines mFOLFOX6 with chemoradiation, offering a multi-faceted approach that could enhance effectiveness. Unlike the standard chemotherapy options, which often rely on single-drug regimens, this treatment uses a combination of 5-Fluorouracil, Leucovorin, and Oxaliplatin to attack cancer cells on multiple fronts. The addition of chemoradiation, which includes Carboplatin and Paclitaxel along with targeted radiation therapy, may increase the overall treatment potency. This integrated approach holds promise for better outcomes compared to traditional therapies.

What evidence suggests that this treatment might be an effective treatment for esophageal cancer?

Research has shown that the mFOLFOX6 chemotherapy treatment, which participants in this trial will receive, can be effective for esophageal cancer. One study found that about 63% of patients experienced a reduction in tumor size. Another study suggested that this treatment could be a viable option for patients unable to undergo surgery, offering a chance for recovery. Although it may not always yield better results compared to some other treatments, it remains a strong option for managing the disease. Overall, these findings suggest that mFOLFOX6 may help shrink tumors and potentially improve survival rates for patients with esophageal cancer. ^{5 6 7 8 9}

Who Is on the Research Team?

Richard Dunne, MD

Principal Investigator

University of Rochester Wilmot Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2579679/

Phase I trial of oxaliplatin with fluorouracil, folinic acid and ... The overall response was 48.5%, including 12% complete response. Response rate on primary tumour was 62.9%. This FOLFOX-4 regimen was reasonably ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0923753419549444

Phase II trial of oxaliplatin, leucovorin and fluorouracil in ... Background: The aim of the study was to evaluate the efficacy and tolerability of the combination of oxaliplatin, fluorouracil and leucovorin in patients ...

3. eviq.org.au eviq.org.au/medical-oncology/upper-gastrointestinal/gastric-and-oesophageal-adjuvant-and-neoadjuvant/1704-oesophageal-definitive-folfox6-modified-fl

Oesophageal definitive FOLFOX6 (modified) (fluorouracil ... Overall survival at 3 years was 19.9% (95% CI 10.8–31.0) in the FOLFOX group and 26.9% (95% CI 16.9–37.8) in the cisplatin-fluorouracil group. ... Health related ...

4. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70028-2/abstract

Definitive chemoradiotherapy with FOLFOX versus ... Definitive chemoradiotherapy is a curative treatment option for oesophageal carcinoma, especially in patients unsuitable for surgery.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5512359/

A Randomized Phase II Study of Leucovorin/5-Fluorouracil ... The addition of oxaliplatin (FOLFOX) did not lead to better efficacy compared to LV5FU2 chemotherapy in an adjuvant setting in node-positive ESCC patients.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9813081/

Safety and short-term efficacy of preoperative FOLFOX ... Preoperative FOLFOX had a manageable safety profile and showed favorable short-term efficacy in patients with resectable LAESCC who were ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6514478/

Combination of Oxaliplatin and 5-Fluorouracil/Leucovorin ... This is the first report suggesting the potential effectiveness of FOLFOX as salvage chemotherapy for metastatic esophageal cancer.

8. nature.com nature.com/articles/s41598-025-92657-7

The efficacy and safety of FOLFOX therapy for advanced ... First-line FOLFOX treatment is suitable for patients with advanced ESCC. However, FOLFOX has shown limited efficacy as a later-line treatment.

9. annalsofoncology.org annalsofoncology.org/article/S0923-7534(22)04349-6/fulltext

122P Efficacy and safety of mFOLFOX-6 in advanced ... This regimen has similar response rates and treatment outcomes with lesser grade 3 or 4 toxicities than that of triplet regimens compared to historical studies.