Chemotherapy + Radiation/Surgery for Stomach Cancer

Overseen By Quynh Nhu Nguyen, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Prior chemotherapy, Radiation therapy, Fistula, Pregnancy, others

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: 4

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining chemotherapy with radiation or surgery is more effective than chemotherapy alone for treating esophageal or stomach cancer that has spread to three or fewer locations in the body. The chemotherapy drugs, fluorouracil and capecitabine, aim to stop cancer cells from growing and spreading. Radiation therapy uses high-energy rays to shrink tumors, while surgery may involve removing tumors or affected organs. Individuals with esophageal or stomach cancer that has spread to a few locations and who have not received previous treatment might be suitable candidates for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people, offering a chance to contribute to important advancements in cancer treatment.

Will I have to stop taking my current medications?

The trial information does not specify if 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 trial's treatments are likely to be safe?

Research has shown that the two main chemotherapy drugs in this study, fluorouracil and capecitabine, are generally well-tolerated by patients with stomach cancer. A large study found that most people can manage the side effects of these drugs. Common side effects include nausea and tiredness, while serious reactions occur less frequently.

When combined with radiation therapy, these drugs maintain their effectiveness, and the side effects remain manageable. Studies indicate that using capecitabine with radiation is as safe as using fluorouracil with radiation.

This trial is in phase 2, building on previous research and focusing on safety and effectiveness. This phase also indicates that earlier tests have shown the treatment to be safe enough for a larger group of participants. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of chemotherapy and radiation or surgery for stomach cancer because it offers a more comprehensive approach to treatment. Unlike standard chemotherapy, which typically involves drugs like fluorouracil alone, this treatment pairs it with capecitabine, potentially enhancing the effectiveness of the chemotherapy. Additionally, the integration of local therapies such as radiation and surgical options allows for a more targeted attack on cancer cells, reducing the likelihood of disease progression. This multi-faceted strategy could lead to improved outcomes and provide a promising alternative to existing treatment protocols.

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

Research has shown that using capecitabine and fluorouracil together effectively treats stomach and other gastrointestinal cancers. In this trial, participants in Group I will receive maintenance chemotherapy with capecitabine and fluorouracil. Studies have found that taking capecitabine as a pill works at least as well as receiving fluorouracil through an IV, helping patients live longer. Participants in Group II will receive capecitabine and fluorouracil combined with radiation therapy and may also undergo surgery as clinically indicated. This combination not only provides similar benefits to other treatments but also keeps side effects low. Overall, these treatments stop cancer cells from growing and spreading. ^{6 7 8 9 10}

Who Is on the Research Team?

Quynh-Nhu Nguyen

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 with esophageal or gastric cancer that has spread to up to three places. They must have a life expectancy of at least six months, be able to perform daily activities (ECOG 0-2), and not have had previous chemotherapy or radiation for this cancer. Women must agree to use birth control during the study.

Inclusion Criteria

My cancer in the esophagus or stomach is confirmed as adenocarcinoma.

The patient has three or less observable metastatic lesions by diagnostic scans (CT scan, PET/CT, eEndoscopic ultrasound, MRI, or bone scan). Metastatic lesions include distant M1 lymph node group; which will be counted as one site (M1 metastatic lymph nodes to include cervical, mediastinal, gastric, retroperitoneal lymph nodes will be counted as one lesion). Osseous metastases or visceral metastases will each count as one metastatic site. Each CNS metastases will count as one metastatic site. Satellite lesions in the primary esophageal malignancy such as skipped esophageal primaries are not considered metastatic sites. Symptomatic metastatic sites can be treated locally prior to randomization or by palliative radiation. Symptomatic metastatic sites may be treated with radiation or surgery prior to enrollment. Patient ECOG of 0-2, with life expectancy of at least 6 months. Patients age >18 yrs old but <80 yrs old and signed informed consent. Women of child-bearing age must have pregnancy test at time of enrollment, agree to use of adequate contraception (birth control hormone or barrier method) for the duration of the study and for six months after discontinuation of systemic agents.

I have 3 or fewer spots of cancer spread that can be seen on scans.

Exclusion Criteria

Patients with fistula documented radiographically or by EDG/EUS, EBUS.

Patients with known hypersensitivity to 5-fluorouracil

I am at risk for severe side effects due to a specific enzyme deficiency.

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 for a minimum of 6 cycles and a maximum of 8 cycles in the absence of disease progression or unacceptable toxicity

12-16 weeks

Randomized Treatment

Participants are randomized to either maintenance chemotherapy or local therapy with chemotherapy and radiation, with possible surgery

Varies based on treatment arm

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 6 years

Follow-up at 4-8 weeks, 2-3 months, every 3-6 months for up to 3 years, then every 6-12 months

What Are the Treatments Tested in This Trial?

Interventions

• Capecitabine
• Conventional Surgery
• Fluorouracil
• Radiation Therapy

Trial Overview The trial is testing if adding radiation therapy or surgery to chemotherapy (with drugs like fluorouracil and capecitabine) provides better outcomes than chemotherapy alone in patients with limited-spread esophageal or gastric cancer.

How Is the Trial Designed?

Group I: Group II (local therapy) Experimental Treatment 5 Interventions

Participants receive fluorouracil and capecitabine and undergo RT per instructions of the treating physician in the absence of disease progression or unacceptable toxicity. Participants may also undergo surgery to some or all of the remaining sites of disease as is clinically prudent and indicated by treating physician.

Group II: Group I (maintenance chemotherapy) Experimental Treatment 3 Interventions

Participants receive fluorouracil and capecitabine per instructions of the treating physician 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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a phase III study involving 485 gastric cancer patients, oral doxifluridine (5'-DFUR) did not show differences in overall or disease-free survival compared to oral 5-fluorouracil (5-FU).

However, 5'-DFUR was found to be more effective in reducing peritoneal recurrence and showed better disease-free survival in patients with Stage III or IIIb gastric cancer compared to those treated with 5-FU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase III randomized study comparing oral doxifluridine and oral 5-fluorouracil after curative resection of gastric cancer. Takiguchi, N., Nakajima, N., Saitoh, N., et al.[2019]

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]

S-1, an oral chemotherapy drug combining tegafur with modulators, has shown advantages over standard 5-FU-based treatments for gastric cancer in large Phase III studies, making it a recommended option in treatment guidelines.

S-1, either alone or in combination with cisplatin, is non-inferior to traditional 5-FU regimens while offering greater convenience and reduced toxicity, highlighting its potential for higher efficacy in treating gastrointestinal cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

S-1 for the treatment of gastrointestinal cancer. Satoh, T., Sakata, Y.[2022]

Xeloda (capecitabine) is an oral medication designed to convert into 5-fluorouracil (5-FU) specifically within tumors, potentially increasing anti-tumor activity while reducing systemic toxicity, as shown in various phase I and II trials.

In a phase II trial for colorectal cancer, Xeloda demonstrated a response rate of 21-24% across different regimens, with good tolerability and a longer time to disease progression for the intermittent regimen, which was selected for further studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential of Xeloda in colorectal cancer and other solid tumors. Cassidy, J.[2017]

In a study of 44 previously untreated patients with advanced gastric cancer, capecitabine demonstrated an objective response rate of 34% and a median overall survival of 9.5 months, indicating its efficacy as a first-line treatment.

Capecitabine was generally well tolerated, with the most common side effects being hand-foot syndrome and nausea, and severe myelosuppression was not observed, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of capecitabine in previously untreated patients with advanced and/or metastatic gastric cancer. Hong, YS., Song, SY., Lee, SI., et al.[2022]

In a study of 46 patients with gastric adenocarcinoma, capecitabine (CA) was found to be better tolerated than 5-fluoro-uracil (FU), with fewer treatment interruptions during concurrent radiotherapy.

Both CA and FU showed similar effectiveness in terms of local control, distant recurrences, and overall survival rates, suggesting that CA can be a viable alternative to FU in postoperative chemoradiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can capecitabine be used instead of concurrent bolus 5-FU in postoperative chemoradiotherapy for gastric adenocarcinoma? Yoney, A., Isikli, L.[2019]

Capecitabine (Xeloda) is an oral chemotherapy that delivers 5-FU directly to tumors, offering superior response rates and equivalent survival outcomes compared to intravenous 5-FU in first-line metastatic colorectal cancer (MCRC).

Capecitabine has a favorable safety profile, with manageable side effects like hand-foot syndrome and diarrhea, allowing for prompt dose adjustments without compromising treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of and clinical experience with capecitabine (Xeloda) in the treatment of solid tumours. Sternberg, CN., Reichardt, P., Holland, M.[2015]

In a study of 108 gastric cancer patients, those receiving concurrent capecitabine and radiation therapy had a longer median recurrence-free survival of 52 months compared to 35 months for those receiving 5-fluorouracil with radiation and 25 months for chemotherapy alone.

Capecitabine combined with radiation therapy demonstrated similar overall survival rates (53 months) compared to 5-fluorouracil with radiation (54 months) and fluoropyrimidine-based chemotherapy alone (44 months), indicating its effectiveness as an adjuvant treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine with radiation is an effective adjuvant therapy in gastric cancers. Tham, CK., Choo, SP., Poon, DY., et al.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/21415237/

Efficacy of Capecitabine Versus 5-fluorouracil in Colorectal ... Conclusions: Oral capecitabine is at least equivalent to i.v. 5-FU in terms of overall survival in patients with gastrointestinal cancers. Capecitabine and 5-FU ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0923753419343595

Efficacy of capecitabine versus 5-fluorouracil in colorectal ... Conclusions. Oral capecitabine is at least equivalent to i.v. 5-FU in terms of overall survival in patients with gastrointestinal cancers. Capecitabine and 5-FU ...

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)34359-5/fulltext

Efficacy of capecitabine versus 5-fluorouracil in colorectal ... Oral capecitabine is at least equivalent to iv 5-FU in terms of overall survival in patients with gastrointestinal cancers.

4. nature.com nature.com/articles/s41598-017-07750-3

Capecitabine, 5-fluorouracil and S-1 based regimens for ... In conclusion, we found no difference in overall survival and progression-free-survival between 5-FU, capecitabine and S-1-based first-line ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1155/2023/4946642

Meta‐Analysis of Capecitabine versus 5‐Fluorouracil in ... Compared with 5-fluorouracil, capecitabine treatment improves the overall response rate and reduces the risk of neutropenia and stomatitis in ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3222088/

Adverse Event Profiles of 5-Fluorouracil and Capecitabine In this study, the safety profiles of oral fluoropyrimidines were compared with 5-FU using more than a million case reports on adverse events (AERs) submitted ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10319465/

Meta-Analysis of Capecitabine versus 5-Fluorouracil in ... Abstract. Objective. To investigate the effect of capecitabine versus 5-fluorouracil in advanced gastric cancer patients.

8. cancer.org cancer.org/cancer/types/stomach-cancer/treating/chemotherapy.html

Stomach (Gastric) Cancer & Chemotherapy Drugs Many different chemo drugs can be used to treat stomach cancer, including: 5-FU (fluorouracil), often given along with leucovorin (folinic acid) ...

9. journals.lww.com journals.lww.com/md-journal/fulltext/2024/03010/comparison_of_efficacy_and_safety_of_5_fu_or.36.aspx

Comparison of efficacy and safety of 5-FU or capecitabine... The 5-year survival rate of gastric cancer is only 20%. Palliative systemic chemotherapy, targeted therapy, and immunotherapy are used to treat ...

10. clinicaltrials.gov clinicaltrials.gov/study/NCT02563054

A Study of Capecitabine (Xeloda) in Participants With ... This study will evaluate the efficacy and safety of oral capecitabine (Xeloda) ... and safety data from the ML17032 phase III clinical trial. Asia Pac J Clin ...