Chemotherapy + Radiation for Esophageal Cancer

Recruiting at 9 trial locations

Overseen By Kebron Elias

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Colorado, Denver

Disqualifiers: Metastatic cancer, Squamous carcinoma, Prior malignancy, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment plan for individuals with cancer in the esophagus or at the junction of the esophagus and stomach. The treatment combines chemotherapy and radiation (known as chemoradiation) before surgery to determine if this approach better prepares the cancer for surgical removal. The trial seeks participants recently diagnosed with this cancer who have not yet received chemotherapy or radiation. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications to join the trial?

The protocol does not specify if you need to stop your current medications. However, since the trial involves chemotherapy and radiation, it's possible that some medications might need to be adjusted. Please consult with the trial coordinators for specific guidance.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the Sequential FLOT treatment, used before surgery for esophageal cancer, can cause some serious side effects. In one study, 65.9% of patients experienced severe reactions, such as low white blood cell counts and infections. Common issues also included tiredness and nerve damage. These side effects are important to consider because they can affect daily life.

The chemoradiation part of the treatment has its own safety profile. In one study, patients who underwent chemoradiation before surgery did not experience a significant increase in harmful effects. This suggests that while the treatment is intense, it does not cause unexpected severe side effects.

Overall, both parts of the treatment carry known risks, which are common for this type of cancer therapy. Understanding these risks is important when considering participation in a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the Sequential FLOT treatment for esophageal cancer because it combines chemotherapy drugs—Docetaxel, Oxaliplatin, and 5-Fluorouracil/Leucovorin—with radiation in a unique sequence. Unlike standard treatments that typically use either chemotherapy or radiation alone, this approach first uses a powerful combo of chemo drugs, followed by targeted chemoradiation with carboplatin and paclitaxel. This strategy could potentially enhance the effectiveness of treatment by maximizing cancer cell kill rates and minimizing resistance, offering hope for improved outcomes in patients with esophageal cancer.

What evidence suggests that this trial's treatments could be effective for esophageal cancer?

Research has shown that the FLOT treatment plan, which includes docetaxel, oxaliplatin, leucovorin, and 5-FU, yields promising results for esophageal cancer. One study found that patients lived for a median of 52 months, with nearly half surviving five years post-treatment. Another study demonstrated that adding docetaxel significantly improved five-year survival rates. In this trial, participants will receive Sequential FLOT followed by chemoradiation. Previous research has shown that using both chemotherapy and radiation for esophageal cancer results in a median survival of 22 months, with some patients remaining cancer-free for up to four years. Combining these treatments aims to improve survival and provide better outcomes for people with esophageal cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Jeffrey Olsen, M.D.

Principal Investigator

University of Colorado, Denver

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed, resectable esophageal or gastroesophageal junction adenocarcinoma who haven't had chemotherapy or radiation. They must be fit enough for triple therapy (chemo, radiation, surgery), have proper kidney and liver function, and not be pregnant. Contraception is required during the study.

Inclusion Criteria

I am a woman who can have children, have a negative pregnancy test, and will use birth control during and 3 months after the study.

My kidney function, measured by creatinine levels, is within the normal range.

My kidney function, based on a formula considering my age, weight, and creatinine levels, is adequate.

Exclusion Criteria

I have a history of hepatitis B or C.

I have no allergies or adverse reactions to the chemotherapy drugs used in this study.

Pregnant or breast-feeding women.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Chemotherapy

Participants receive induction chemotherapy using a combination of docetaxel, oxaliplatin, leucovorin, and short-term infusional 5-FU (FLOT)

8-12 weeks

Neoadjuvant Chemoradiation

Participants undergo chemoradiotherapy with concurrent carboplatin and paclitaxel as neoadjuvant therapy

5-6 weeks

Surgical Resection

Definitive surgical resection is performed for patients with adenocarcinoma of the esophagus or gastroesophageal junction

Follow-up

Participants are monitored for safety and effectiveness after treatment, including evaluation of pathologic complete response and survival outcomes

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Chemoradiation
• Sequential FLOT

Trial Overview The trial tests a new treatment sequence starting with FLOT chemotherapy (docetaxel, oxaliplatin, leucovorin, 5-FU) followed by chemoradiation using carboplatin and paclitaxel before surgical removal of the cancer.

How Is the Trial Designed?

Group I: Sequential FLOT followed by chemoradiation Experimental Treatment 1 Intervention

Sequential Chemotherapy with Docetaxel, Oxaliplatin, and 5-Fluorouracil/Leucovorin followed by chemoradiation with concurrent carboplatin and paclitaxel

Sequential FLOT is already approved in European Union, United States for the following indications:

Approved in European Union as FLOT for:

• Esophageal adenocarcinoma
• Gastroesophageal junction adenocarcinoma

Approved in United States as FLOT for:

• Locally advanced esophageal adenocarcinoma

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

American Cancer Society, Inc.

Collaborator

Trials

237

Recruited

110,000+

Cancer League of Colorado

Collaborator

Trials

13

Recruited

450+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

This phase-II study aims to evaluate the safety and feasibility of a combined FLOT and CROSS treatment regimen in 20 patients with oligometastatic esophageal adenocarcinoma, focusing on whether patients can tolerate the full treatment course.

If the FLOT-CROSS regimen is well-tolerated, it may lead to further testing in larger phase-III trials for neoadjuvant treatment in patients with locally advanced non-metastatic esophageal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy aNd chemoradiotherapy for adenocarcinoma of the OESophagus and esophagogastric junction with oligometastases: Protocol of the TNT-OES-1 trial. van der Zijden, CJ., Eyck, BM., van der Gaast, A., et al.[2023]

In a study of 222 patients with locally advanced esophageal adenocarcinoma, both the FLOT and CROSS treatment regimens showed similar survival rates (around 60-63%) but differed in tolerance and side effects, with only 40% of patients completing the FLOT regimen compared to 92% for CROSS.

While both regimens had comparable operative outcomes, the CROSS regimen was associated with a higher risk of postoperative respiratory failure (13% vs. 3% for FLOT), suggesting that caution is needed when using CROSS in patients with pre-existing respiratory issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CROSS Versus FLOT Regimens in Esophageal and Esophagogastric Junction Adenocarcinoma: A Propensity-Matched Comparison. Donlon, NE., Moran, B., Kamilli, A., et al.[2022]

The FLOT regimen for treating esophagogastric tumors shows similar efficacy to other docetaxel-based regimens in terms of pathological complete response, resection rate, and survival outcomes, based on a meta-analysis of 16 studies involving over 1,000 patients.

Despite comparable effectiveness, the docetaxel regimens are associated with high toxicity rates, with 50-70% of patients experiencing severe neutropenia, highlighting the need for future trials to develop less toxic treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review and meta-analysis of docetaxel perioperative chemotherapy regimens in gastric and esophagogastric tumors. Uson Junior, PLS., Santos, VM., Bugano, DDG., et al.[2021]

In a phase II study involving 16 patients with inoperable locally advanced esophageal squamous cell carcinoma, the chemoradiotherapy regimen using docetaxel and 5-fluorouracil showed a high response rate of 94%, with 31% achieving complete response.

The treatment was found to be safe, with mild hematologic toxicity and manageable nonhematologic side effects, leading to a median progression-free survival of 20 months and 3-year and 5-year survival rates of 44% and 31%, respectively.

NCBI (Pubmed)

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. Hihara, J., Hamai, Y., Emi, M., et al.[2022]

The CROSS protocol for chemoradiotherapy resulted in a significantly higher rate of complete pathological response in patients with distal esophageal and gastroesophageal junction tumors compared to the FLOT regimen, with 32% of CROSS patients achieving complete response versus none in the FLOT group.

Both CROSS and FLOT protocols provided similar two-year survival rates for patients with gastroesophageal junction adenocarcinoma, but the CROSS group experienced significantly more neutropenia, indicating a higher risk of hematological side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CROSS or FLOT in Distal Esophageal and Gastroesophageal Cancer. Karadag, I., Karakaya, S., Ates, O., et al.[2021]

In a study of 277 patients with non-metastatic esophagogastric cancer treated with the FLOT protocol, the median survival was 61 months, and the postoperative in-hospital mortality rate was low at 2%.

Recurrence after treatment predominantly occurred within the first 24 months, with gastric cancer mostly recurring as peritoneal carcinomatosis (56%) and esophageal cancer as distant organ metastasis (78%), but the site of recurrence did not affect overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pattern of Recurrence and Patient Survival after Perioperative Chemotherapy with 5-FU, Leucovorin, Oxaliplatin and Docetaxel (FLOT) for Locally Advanced Esophagogastric Adenocarcinoma in Patients Treated Outside Clinical Trials. Glatz, T., Verst, R., Kuvendjiska, J., et al.[2020]

In a study of 593 patients with esophagogastric adenocarcinomas, the modified FLOT (mFLOT) regimen showed significantly better 3-year event-free survival (60%) compared to the EOX regimen (39%), indicating mFLOT's superior efficacy as perioperative therapy.

While mFLOT improved resection rates (86% vs. 76% for EOX), it was associated with a higher incidence of severe neutropenia and febrile neutropenia, suggesting that while mFLOT is more effective, it also carries a risk of increased toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative Modified FLOT Versus EOX in Locally Advanced Resectable Gastric and Gastro-Oesophageal Junction Adenocarcinoma: Results of a Matched-Pair Analysis. Ramaswamy, A., Bhargava, P., Srinivas, S., et al.[2023]

In a study comparing perioperative FLOT chemotherapy to the ECX/ECF regimen in patients with resectable oesophagogastric adenocarcinoma, FLOT was associated with a shorter median hospital stay after surgery (12 days vs. 15 days, P=0.035).

Both FLOT and ECX/ECF showed similar rates of overall perioperative complications and specific complications like anastomotic leaks, indicating that FLOT is as safe as the traditional ECX/ECF regimen for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of perioperative FLOT versus ECF/ECX on short-term outcomes after surgery for resectable oesophagogastric adenocarcinoma: propensity score-matched study. Moussa, O., Bhogal, RH., Malietzis, G., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2684724/

Chemoradiotherapy for Esophageal Cancer - PMC This regimen achieved an encouraging median survival of 22 months in the 22 patients treated; 6 of these patients were alive and disease free at 40 to 46 months ...

2. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(25)00364-5/fulltext?rss=yes

a systematic review and hierarchical Bayesian meta-analysis High-dose radiotherapy significantly improved LRPFS, with the largest benefit observed at 1-year (median difference: 18.6%; 95% credible ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2331518024000751

Esophageal Cancer Outcomes After Definitive ... At a median follow-up time of 39 months, the 5-year overall survival rate was 41.1%; progression-free survival, 34.6%; local regional recurrence-free survival, ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9801454/

Clinical Outcomes of Definitive Chemoradiotherapy for ... Patients with cervical esophageal carcinoma in Nagasaki University Hospital in Japan achieved superior outcomes compared with previous studies.

5. cancernetwork.com cancernetwork.com/view/tislelizumab-shows-improvements-in-efficacy-vs-chemo-in-esophageal-cancer

Tislelizumab Shows Improvements in Efficacy Vs Chemo ... Data from the RATIONALE 302 trial indicated a median overall survival of 8.6 months (95% CI, 7.5-10.4) in the tislelizumab arm vs 6.3 months (95 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5177593/

Phase II study of bevacizumab and preoperative ... Twenty-eight patients completed chemoradiation and 26 patients underwent surgery (25 R0 resections). Toxicities were not clearly increased. The pathologic ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35442766/

Tislelizumab Versus Chemotherapy as Second-Line ... Tislelizumab significantly improved OS compared with chemotherapy as second-line therapy in patients with advanced or metastatic ESCC, with a tolerable safety ...

8. esmoopen.com esmoopen.com/article/S2059-7029(23)01443-6/fulltext

Tislelizumab versus chemotherapy as second-line ... As a 2L therapy for advanced/metastatic ESCC, tislelizumab improved OS and had a favorable safety profile as compared to chemotherapy in ...

9. jtd.amegroups.org jtd.amegroups.org/article/view/101892/html

Assessment of efficacy, safety and survival of tislelizumab as ... Tislelizumab in combination with neoadjuvant chemotherapy is safe and effective in patients with locally advanced esophageal squamous cell carcinoma (ESCC).

10. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2798101

Evaluation of Clinical and Safety Outcomes of Neoadjuvant ... Most patients achieved R0 surgical resection (98.6%; 95% CI, 97.1%-99.6%). Regarding histologic subtypes, the pooled pCR rates were 32.4% (95% ...