Chemotherapy + Radiotherapy for Esophageal and Gastric Cancer

Recruiting at 482 trial locations

Overseen By Nataliya V Uboha

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: ECOG-ACRIN Cancer Research Group

Disqualifiers: CNS metastasis, Uncontrolled illness, Pregnancy, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

314 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding radiotherapy to standard chemotherapy improves treatment for esophageal and gastric cancer that has spread to a few areas. Radiotherapy uses high-energy rays to target and kill cancer cells. Participants will receive various combinations of chemotherapy drugs, such as Capecitabine, Fluorouracil, Leucovorin, and Oxaliplatin, along with radiotherapy to determine the most effective approach. This trial may suit individuals with HER2 negative esophageal or gastric cancer with limited metastasis who have not undergone significant prior treatment with the same chemotherapy drugs being tested. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I have to stop taking my current medications for the trial?

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 to get specific guidance based on your situation.

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

Research shows that the treatments in this trial have promising safety records. Patients with advanced esophageal and gastric cancer have generally tolerated the FOLFOX regimen well, though side effects like nausea and fatigue can occur. Some patients have experienced cancer stabilization or partial response to the treatment.

The CAPOX regimen, which includes capecitabine and oxaliplatin, has also undergone extensive research. Earlier studies found serious side effects to be rare, with only 7% of patients experiencing severe issues. Most patients managed the treatment well, though some reported mild to moderate side effects like diarrhea and hand-foot syndrome, which causes redness and swelling in the hands and feet.

Radiotherapy, another part of this trial, has been used safely and effectively for esophageal cancer. Some studies suggest that proton therapy, a type of radiotherapy, might have fewer side effects than other forms. However, combining radiotherapy with chemotherapy can increase the risk of side effects like fatigue and esophagitis, which is inflammation of the esophagus.

Overall, while these treatments have known side effects, they are generally manageable. Potential trial participants should discuss all possible risks and benefits with their healthcare providers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for esophageal and gastric cancer because they combine chemotherapy with radiotherapy in innovative ways. Unlike standard treatments that typically involve chemotherapy alone, these experimental arms integrate drugs like oxaliplatin, leucovorin, and fluorouracil with radiation to potentially enhance effectiveness. The CAPOX regimen also introduces capecitabine, an oral chemotherapy drug, which may offer more convenience compared to traditional intravenous methods. By combining these approaches, there's hope for improved outcomes and more personalized treatment options for patients.

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

This trial will evaluate the effectiveness of different chemotherapy and radiotherapy combinations for esophageal and gastric cancer. Studies have shown that combining chemotherapy and radiotherapy can improve outcomes for these cancers. In this trial, participants in Arm A will receive the FOLFOX treatment, which includes oxaliplatin, leucovorin, and 5-fluorouracil. Research indicates that FOLFOX is effective for advanced gastric cancer, often leading to significant tumor shrinkage and longer periods without cancer progression. Participants in Arm B will receive the CAPOX treatment, which combines capecitabine and oxaliplatin. CAPOX has demonstrated similar effectiveness, with good response rates and benefits for esophagogastric cancer. Additionally, some participants will receive radiation therapy alongside these chemotherapy regimens, as seen in Arms C and E, which can enhance the effects of chemotherapy and potentially improve survival rates. Combining these treatments might offer a better chance of controlling cancer that has spread to a few other areas. ^{2 4 6 7 8}

Who Is on the Research Team?

Nataliya V Uboha

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

This trial is for adults with HER2 negative esophageal or gastric adenocarcinoma that has spread to up to 3 other body parts. They should have stable disease after certain chemotherapy treatments and be in good physical condition (ECOG 0-1). Participants need functioning major organs, not be pregnant or breastfeeding, and agree to use contraception. Those with uncontrolled illnesses, CNS metastasis, prior adverse reactions to the study drugs, or recent live vaccines cannot join.

Inclusion Criteria

My cancer has spread to the lymph nodes in my chest.

I am using or willing to use effective birth control after my last treatment dose.

Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3.0 x upper limit of normal (ULN)

Exclusion Criteria

I have not received any live vaccines in the last 30 days.

I have no health issues preventing radiation therapy, as confirmed by a radiation oncologist.

I am of childbearing age and have a negative pregnancy test within the last 14 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Patients receive chemotherapy with either FOLFOX or CAPOX regimen to assess response before randomization

12-24 weeks

Radiation

Patients undergo radiation therapy for up to 15 days, followed by continuation of chemotherapy

2-4 weeks

Consolidation

Patients continue chemotherapy with or without radiation therapy for up to 2 years

2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Capecitabine
• Fluorouracil
• Leucovorin
• Oxaliplatin
• Radiation Therapy

Trial Overview The study is testing if adding radiotherapy (high energy rays) to standard chemotherapy (leucovorin calcium, fluorouracil/5-FU, oxaliplatin) improves outcomes for patients with limited-spread esophageal and gastric cancer compared to chemotherapy alone. It's a phase III trial where participants are randomly assigned treatment options.

How Is the Trial Designed?

Group I: Arm E (radiation therapy, CAPOX) Experimental Treatment 3 Interventions

One week post induction of patients in ARM B, patients undergo radiation therapy for up to 15 days. Within 2-4 weeks post radiation therapy, patients receive oxaliplatin and capecitabine as in Arm B for 2 years in the absence of disease progression or unacceptable toxicity.

Group II: Arm C (radiation therapy, FOLFOX) Experimental Treatment 5 Interventions

One week post induction of patients in ARM A, patients undergo radiation therapy for up to 15 days. Within 2-4 weeks post radiation therapy, patients receive oxaliplatin, leucovorin, and 5-fluorouracil as in Arm A for 2 years in the absence of disease progression or unacceptable toxicity.

Group III: Arm B (CAPOX) Experimental Treatment 2 Interventions

Patients receive oxaliplatin IV over 2 hours on day 1 and capecitabine PO BID on days 1-14. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Group IV: Arm A (FOLXFOX) Experimental Treatment 4 Interventions

Patients receive oxaliplatin IV over 1.5 hours, leucovorin IV over 1.5 hours, and 5-fluorouracil IV over 46-48 hours on days 1 and 15. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

Group V: Arm D (FOLFOX) Active Control 4 Interventions

Post induction of patients in ARM A, patients continue oxaliplatin, leucovorin, and 5-fluorouracil as in Arm A for 2 years in the absence of disease progression or unacceptable toxicity.

Group VI: Arm F (CAPOX) Active Control 2 Interventions

Post induction of patients in ARM B, patients continue oxaliplatin and capecitabine as in Arm B for 2 years in the absence of disease progression or unacceptable toxicity.

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

Approved in European Union as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in United States as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Canada as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Japan as Xeloda for:

• Colorectal cancer
• Breast cancer

Who Is Running the Clinical Trial?

ECOG-ACRIN Cancer Research Group

Lead Sponsor

Trials

122

Recruited

160,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a clinical trial involving 142 patients with advanced esophageal squamous cell cancer, adding panitumumab to cisplatin and 5-fluorouracil (CFP) did not improve overall survival compared to CF alone, with median survival times of 10.2 months for CF versus 9.4 months for CFP.

The trial was stopped early due to interim results showing that patients receiving CFP had a higher risk of death related to disease progression, and more serious adverse events were reported in the CFP group, indicating that the addition of EGFR inhibition may not be beneficial in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cisplatin and 5-fluorouracil with or without epidermal growth factor receptor inhibition panitumumab for patients with non-resectable, advanced or metastatic oesophageal squamous cell cancer: a prospective, open-label, randomised phase III AIO/EORTC trial (POWER). Moehler, M., Maderer, A., Thuss-Patience, PC., et al.[2022]

A modified radiochemotherapy regimen for esophageal cancer, involving leucovorin, 5-fluorouracil, and cisplatin, was well tolerated by 33 patients, with a complete response rate of 70%.

The treatment resulted in a median overall survival of 14 months and a 2-year survival rate of 40%, indicating its efficacy, while allowing for outpatient administration for more than one-third of treatment cycles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemoradiotherapy for cancer of the esophagus: contribution of the leucovorin, 5-fluorouracil bolus, and infusion-cisplatin-radiotherapy schedule starting with two neoadjuvant chemotherapy cycles: results from a pilot study. Tran Vuong, TN., Le Prisé, E., Vauléon, E., et al.[2016]

In a study of 1002 patients with untreated advanced esophagogastric cancer, capecitabine was found to be noninferior to fluorouracil in terms of overall survival, with a hazard ratio of 0.86, indicating it is an effective alternative.

Oxaliplatin demonstrated similar efficacy to cisplatin, with a hazard ratio of 0.92, and was associated with fewer severe side effects, making it a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine and oxaliplatin for advanced esophagogastric cancer. Cunningham, D., Starling, N., Rao, S., et al.[2023]

In a Phase I study involving 12 patients with advanced esophageal cancer, the combination of UFT/leucovorin, carboplatin, and paclitaxel with radiation therapy showed preliminary efficacy, with 2 out of 3 patients achieving a pathologic complete response after treatment at the higher dose level.

The study identified maximum tolerated doses for the regimen, but also noted significant toxicity, including febrile neutropenia in multiple patients, indicating that while the treatment may be effective, it carries a risk of serious side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of UFT/leucovorin, carboplatin, and paclitaxel in combination with external beam radiation therapy for advanced esophageal carcinoma. Czito, BG., Cohen, DP., Kelsey, CR., et al.[2015]

In a phase II trial involving 24 patients with resectable esophageal carcinoma, the combination of neoadjuvant therapy using paclitaxel, carboplatin, 5-fluorouracil, and conformal radiotherapy resulted in a 57% pathologic complete response rate, indicating significant effectiveness in shrinking tumors before surgery.

The treatment showed a median overall survival of 31 months and a disease-free survival rate of 57% at 3 years, although some patients experienced significant side effects, including esophagitis and hypotension, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant chemoradiotherapy for esophageal cancer using weekly Paclitaxel and Carboplatin plus infusional 5-Fluorouracil. Gannett, DE., Wolf, RF., Takahashi, GW., et al.[2022]

Capecitabine is an effective oral prodrug for fluorouracil, providing patients with greater convenience and fewer complications compared to traditional infusion therapies, and has been extensively studied in various solid tumors with a favorable safety profile.

While capecitabine can cause gastrointestinal issues and hand-foot syndrome, its overall tolerability is better than that of fluorouracil, and ongoing clinical trials are expected to further explore its use in combination therapies for gastrointestinal and other solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting cancers in the gastrointestinal tract: role of capecitabine. Saif, MW.[2021]

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]

In a study of 50 patients with nonmetastatic colorectal cancer, adverse reactions were more frequent with the XELOX regimen (capecitabine combined with oxaliplatin), particularly neurotoxicity, thrombocytopenia, and neutropenia, compared to capecitabine monotherapy.

The type of capecitabine formulation (innovative vs. generic) did not significantly affect the safety profile; instead, the chemotherapy scheme used was the main factor influencing the occurrence of adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine safety profile, innovative and generic adjuvant formulation of nonmetastatic colorectal cancer. Sánchez-Gundín, J., Torres-Suárez, AI., Fernández-Carballido, AM., et al.[2020]

Capecitabine, an oral medication, showed at least equivalent efficacy to intravenous 5-FU plus leucovorin in treating metastatic colorectal cancer, with an overall response rate of 18.9% compared to 15.0% for 5-FU/LV among 602 patients.

Capecitabine had a more favorable safety profile, resulting in significantly lower rates of stomatitis and neutropenia, while being associated with a higher incidence of hand-foot syndrome, making it a convenient and effective alternative to traditional IV treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. Van Cutsem, E., Twelves, C., Cassidy, J., et al.[2022]

Capecitabine, an oral prodrug of 5-fluorouracil, has been shown to be an effective and convenient alternative to infusional 5-FU in the treatment of esophageal, stomach, and pancreatic cancers when combined with irradiation.

Research is ongoing into the benefits of adding a COX-2 inhibitor to treatment regimens for upper gastrointestinal cancers, as these cancers often show high levels of COX-2 expression, which may enhance therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

COX-2 inhibitors as radiation sensitizers for upper GI tract cancers: esophagus, stomach, and pancreas. Rich, TA., Shepard, R.[2015]

In a study of 35 patients with advanced esophageal cancer, the combination of oxaliplatin, leucovorin, and fluorouracil demonstrated a 40% overall response rate, indicating significant anti-tumor activity.

While the treatment was effective, it also had notable side effects, including a 29% incidence of severe neutropenia and 26% experiencing significant peripheral neuropathy, highlighting the need for careful monitoring of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of oxaliplatin, leucovorin and fluorouracil in patients with advanced carcinoma of the esophagus. Mauer, AM., Kraut, EH., Krauss, SA., et al.[2020]

A regimen of accelerated hyperfractionated radiotherapy combined with low-dose cisplatin and continuous infusion fluorouracil showed effectiveness in treating locally advanced squamous cell carcinoma of the esophagus, resulting in a median survival of 28 months and a 5-year survival rate of 38%.

Patients who achieved a pathological complete response had significantly better outcomes, with a median survival of 132 months and a 5-year survival rate of 72%, indicating the importance of treatment response in predicting long-term survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative low-dose weekly cisplatin and continuous infusion fluorouracil plus hyperfractionated radiotherapy in stage II-III esophageal carcinoma. Caro, M., Font, A., Comas, S., et al.[2019]

Citations

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A phase II study of capecitabine plus 3-weekly oxaliplatin ... Our study shows that the XELOX regimen achieved a very good response rate and PFS in patients with advanced gastric cancer. Two patients achieved a complete ...

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FG-M108 plus capecitabine and oxaliplatin (CAPOX) for ... This phase I/II trial evaluated safety, pharmacokinetics and preliminary antitumor activity of FG-M108 plus CAPOX in previously untreated pts with CLDN18.2+/ ...

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Combined treatment of oxaliplatin and capecitabine in ... The effectiveness rate was 40.6% and the overall clinical benefit rate was 84.4%. Toxic and side effects. The main side effects of chemotherapy were alimentary ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2405844024151833

Capecitabine enhances sensitivity to oxaliplatin in ... Capecitabine effectively enhanced the sensitivity of intermediate and advanced gastric cancer to oxaliplatin, improved the therapeutic effect.

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First-line treatment with oxaliplatin and capecitabine in ... This phase II study assessed the safety and efficacy of oxaliplatin and capecitabine in patients with advanced oesophageal cancer.

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Comparison of capecitabine plus oxaliplatin (CAPOX) vs ... Conclusions: There were more disease progression in CapOx arm but both arms did not show significant differences in survival outcome. There were ...

8. asco.org asco.org/abstracts-presentations/ABSTRACT77463

Adjuvant capecitabine and oxaliplatin for gastric cancer Serious XELOX-related grade 3/4 AEs occurred in 34/496 patients (7%). There were 62/496 (13%) and 80/476 (17%) deaths on study in the safety populations of ...