Chemotherapy + Radiation for Esophageal Cancer

Recruiting in Palo Alto (17 mi)

+9 other locations

Overseen by Jeffrey Olsen, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of Colorado, Denver

Disqualifiers: Metastatic cancer, Squamous carcinoma, Prior malignancy, others

Stay on Your Current Meds

No Placebo Group

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This study evaluates a novel regimen of induction chemotherapy using a combination of docetaxel, oxaliplatin, and leucovorin, with short term infusional 5-FU (FLOT), given prior to chemoradiotherapy with concurrent carboplatin and paclitaxel, as neoadjuvant therapy prior to definitive surgical resection for patients with adenocarcinoma of the esophagus or gastroesophageal junction

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.

What data supports the idea that Chemotherapy + Radiation for Esophageal Cancer is an effective treatment?

The available research shows that Chemotherapy + Radiation, specifically the CROSS regimen, is effective for treating esophageal cancer. It achieves a good local response, with up to 33% of patients experiencing a complete response, meaning the cancer is no longer detectable. When compared to the FLOT regimen, which is another chemotherapy approach, CROSS is noted for its effectiveness in managing locally advanced esophageal cancer. Additionally, the FLOT regimen is highlighted for improving survival rates in patients with esophagogastric cancer, suggesting that both treatments have their strengths in different aspects of cancer management.

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What safety data exists for chemotherapy and radiation treatment for esophageal cancer?

The safety data for chemotherapy and radiation treatment, including regimens like FLOT and CROSS, show varying levels of toxicity. The FLOT regimen, which includes 5-FU, leucovorin, oxaliplatin, and docetaxel, is noted for its effectiveness but also for significant toxicity, with up to 50-70% of patients experiencing grade 3-4 neutropenia. The CROSS regimen, used for neoadjuvant chemoradiotherapy, achieves good locoregional response rates. A phase II study of definitive chemoradiotherapy using docetaxel and 5-fluorouracil reported mild hematologic toxicity and some nonhematologic adverse events like esophagitis and anorexia, but no treatment-related deaths. Overall, while these treatments are effective, they are associated with notable toxicities, and further trials are needed to develop less toxic strategies.

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Is Sequential FLOT a promising drug for esophageal cancer?

Yes, Sequential FLOT is a promising drug for esophageal cancer. It has shown superior results in treating non-metastatic esophagogastric cancer compared to other treatments. It is effective in improving patient survival and reducing cancer recurrence.

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Eligibility Criteria

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.

Trial Timeline

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

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University of Colorado Hospital Aurora, CO

UCHealth Southern Colorado - Memorial Hospital Central Colorado Springs, CO

UCHealth Southern Colorado - Memorial Hospital North Colorado Springs, CO

UCHealth Northern Colorado - Poudre Valley Hospital Fort Collins, CO

More Trial Locations

Who Is Running the Clinical Trial?

University of Colorado, Denver Lead Sponsor

American Cancer Society, Inc. Collaborator

Cancer League of Colorado Collaborator

National Cancer Institute (NCI) Collaborator

References

1. Pakistan pubmed.ncbi.nlm.nih.gov

CROSS or FLOT in Distal Esophageal and Gastroesophageal Cancer. [2021] To compare the chemoradiotherapy for esophageal cancer followed by surgery study (CROSS) and continuous infusion 5-FU, leucovorin, oxaliplatin, and docetaxel (FLOT) protocols administered in distal esophageal and gastroesophageal junction (GEJ) tumors in terms of effectiveness and toxicity.

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

CROSS Versus FLOT Regimens in Esophageal and Esophagogastric Junction Adenocarcinoma: A Propensity-Matched Comparison. [2022] The FLOT protocol and the CROSS trimodality regimen represent current standards in the management of locally advanced esophageal adenocarcinoma. In the absence of published Randomised Controlled Trial data, this propensity-matched comparison evaluated tolerance, toxicity, impact on sarcopenia and pulmonary physiology, operative complications, and oncologic metrics.

3. Netherlands 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. [2023] FLOT and CROSS are effective neoadjuvant regimens for esophageal cancer patients. Chemotherapy (FLOT) is aimed to have merely a systemic effect whereas neoadjuvant chemoradiotherapy (CROSS) achieves good locoregional response with clinically complete response (cCR) rates up to 33% [1]. The aim of the present study is to assess safety and feasibility of dual therapy (FLOT-CROSS) in patients with oligometastases.

4. Switzerland 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. [2020] The 5-FU, Leucovorin, Oxaliplatin and Docetaxel (FLOT) protocol provides superior oncologic results compared to other perioperative chemotherapeutic protocols for the treatment of non-metastatic esophagogastric cancer (EGAC). Survival and the pattern of recurrence of EGAC after FLOT and curative tumor resection are analyzed in a collective of patients treated outside clinical trials.

5. England 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. [2022] Perioperative FLOT (fluorouracil plus leucovorin, oxaliplatin, and docetaxel) chemotherapy is a recent regimen used to treat resectable oesophagogastric (OG) adenocarcinoma, associated with improved overall survival versus earlier chemotherapy strategies. This study compared short-term perioperative morbidity in a large tertiary centre series of FLOT to a matched cohort receiving ECX/ECF (epirubicin, cisplatin, capecitabine (X) or 5-fluorouracil (F)).

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

Systematic review and meta-analysis of docetaxel perioperative chemotherapy regimens in gastric and esophagogastric tumors. [2021] FLOT regimen became the standard perioperative treatment in several centers around the world for esophagogastric tumors despite concerns about toxicity. In addition, FLOT has never been compared with other docetaxel-based regimens. To address this question, we conducted a systematic review of PubMed, Embase and Web of Science including prospective or retrospective studies of docetaxel based perioperative regimen in gastric and esophagogastric tumors. Data regarding chemotherapy regimens, efficacy and toxicity were extracted. Outcomes were compared using a random effects model. Of 548 abstracts, 16 were considered eligible. Comparing the studies with meta-analysis we can see that the regimens are similar in terms of pathological complete response, resection rate, progression free survival and overall survival in one year, without significant heterogeneity. The meta-regression of docetaxel dose failed to show any association with dose ranging between 120-450 mg/m². Regarding the toxicity of the regimens it is noted that the regimens are quite toxic (up to 50-70% of grade 3-4 neutropenia). The results of this meta-analysis with a combined sample size of more than 1,000 patients suggest that docetaxel perioperative regimens are equivalent in outcomes. Prospective trials addressing modified regimens should be performed to provide less toxic strategies and be applicable to all patients.

7. 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.

8. United States 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. [2023] There is limited real-world data on the efficacy of 2-weekly cycles of docetaxel, oxaliplatin, leucovorin, and fluorouracil (FLOT) compared to epirubicin, oxaliplatin, and capecitabine (EOX) as perioperative therapy in esophagogastric adenocarcinomas (EGAC).