Chemoradiotherapy + Chemotherapy for Gastric Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Metastatic disease, Malabsorption syndromes, Infections, Pregnancy, Unstable angina, others

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

Compensation: Varies

Number of Visits: 16

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a shorter, two-week course of combined chemotherapy and radiation (chemoradiotherapy), followed by standard chemotherapy, effectively treats gastric cancer. The focus is on patients scheduled for surgery to remove their stomach tumor, aiming to better control the disease before surgery. Potential participants must have a confirmed diagnosis of stomach cancer without signs of spreading to other parts of the body. The trial involves chemotherapy drugs like capecitabine (Xeloda) and fluorouracil (5-Fluorouracil or 5-FU), along with radiation therapy, to shrink tumors before surgery. As a Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants a chance to be among the first to receive this innovative approach.

Do I need to stop my current medications for this 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.

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

Research has shown that capecitabine is generally well tolerated by patients with stomach cancer. It is commonly used and considered safe for treating several types of cancer, including stomach cancer. One study found that using capecitabine as the first treatment option was well tolerated by patients with advanced stomach cancer.

For fluorouracil, another study highlighted a safety warning for patients with a specific genetic issue (DPD deficiency), which could cause severe reactions. However, when used correctly, it is generally safe when combined with other cancer treatments.

Radiation therapy is effective but can cause side effects like tiredness or skin irritation. These usually subside a few weeks after treatment ends. Studies have shown that radiation therapy can greatly improve outcomes for stomach cancer patients.

Overall, these treatments are generally safe when monitored by healthcare professionals. Patients should always discuss possible side effects with their doctor to understand their implications. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for gastric cancer because it combines chemoradiotherapy with chemotherapy and surgery in a unique sequence. Unlike standard treatments, which typically involve separate administration of chemotherapy and surgery, this approach integrates radiation therapy with chemotherapy upfront. This combination aims to shrink tumors more effectively before surgical removal, potentially improving outcomes. Additionally, the use of capecitabine or fluorouracil during radiation may enhance the cancer-killing effects, offering a promising strategy for managing gastric cancer.

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

In this trial, participants will receive chemoradiotherapy with either capecitabine or fluorouracil (5-FU) alongside radiation therapy. Research has shown that using capecitabine with radiation effectively treats stomach cancer by stopping its growth and improving survival rates. Similarly, combining fluorouracil (5-FU) with radiation has improved survival and reduced cancer recurrence. Specifically, one study found that using 5-FU with radiation increased the 3-year survival rate to 86%. Both treatments in this trial aim to shrink tumors and control the disease before surgery. ^{2 3 6 7 8}

Who Is on the Research Team?

Brian Badgwell, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with confirmed gastric adenocarcinoma who are fit enough for chemotherapy and surgery, have a good kidney function (eGFR >= 60 mL/min/1.73 m^2), no distant cancer spread, and an ECOG performance status of <=2. Pregnant women, those unable to follow the study plan, people with life-threatening reactions to similar chemo drugs or prior radiotherapy in the same area, and individuals with certain health conditions that make treatment risky are excluded.

Inclusion Criteria

I have been diagnosed with stomach cancer through a biopsy.

My kidney function is normal or only mildly reduced.

My cancer is at least stage T2 or has spread to the lymph nodes.

Exclusion Criteria

My scans show cancer has spread, but I haven't had or can't have a laparoscopy due to past surgery.

I have health conditions that prevent me from receiving certain cancer treatments.

I am not pregnant, will not breastfeed, and will use effective birth control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemoradiotherapy

Participants receive radiation therapy 5 days a week for 2 weeks and standard of care chemotherapy

2 weeks

10 visits (in-person)

Chemotherapy

Participants receive standard of care chemotherapy for up to 2 months

8 weeks

Surgery

Participants undergo standard of care surgery 3-8 weeks post-chemotherapy completion

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Capecitabine
• Fluorouracil
• Radiation Therapy
• Therapeutic Surgical Procedure

Trial Overview The trial tests if a shorter course of chemoradiotherapy over 2 weeks followed by standard chemotherapy before surgery can effectively treat stomach cancer. It uses capecitabine and fluorouracil—drugs that target tumor cells—to see if this approach better controls the disease compared to longer treatments.

How Is the Trial Designed?

Group I: Treatment (CXRT, chemotherapy, surgery) Experimental Treatment 4 Interventions

Patients receive CXRT consisting of radiation therapy 5 days a week (Monday through Friday) for 2 weeks (10 treatments) and standard of care chemotherapy consisting of capecitabine PO BID or fluorouracil IV continuous Monday to Friday of each radiation week. About 2 weeks later, patients receive standard of care chemotherapy for up to 2 months in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery 3-8 weeks post-chemotherapy completion.

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

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]

In a phase II study involving 54 patients with locally advanced rectal cancer, the combination of capecitabine and radiotherapy resulted in a pathologic complete response rate of 18% and a significant downstaging of tumors in 51% of patients, indicating its efficacy as a neoadjuvant treatment.

The treatment was well tolerated, with manageable side effects, and showed a sphincter preservation rate of 67% for tumors located close to the anal verge, making it a convenient alternative to traditional 5-FU infusion methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of capecitabine (Xeloda) and concomitant boost radiotherapy in patients with locally advanced rectal cancer. Krishnan, S., Janjan, NA., Skibber, JM., 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]

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]

Combining capecitabine (an oral fluoropyrimidine) with radiation therapy shows promise as a more convenient and effective approach for treating gastrointestinal cancers, with ongoing studies examining its efficacy compared to infusional fluorouracil (5-FU).

Capecitabine's activation to 5-FU is enhanced by thymidine phosphorylase, which is more active in tumor tissues, potentially leading to better drug accumulation in tumors and improved outcomes in radiation therapy, as indicated by ongoing and planned clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine and radiation therapy for advanced gastrointestinal malignancies. Rich, T.[2015]

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 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]

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]

The combination of irinotecan and capecitabine (XELIRI) was found to be effective in treating advanced colorectal adenocarcinoma, with a median survival of 16 months and a 30% partial response rate among 40 patients.

XELIRI was well-tolerated, with common side effects being leukopenia and gastrointestinal issues, making it a more convenient option compared to traditional intravenous chemotherapy regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan plus capecitabine as first-line chemotherapy in advanced colorectal cancer. Gennatas, C., Michalaki, V., Gennatas, S., et al.[2018]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2915433/

Capecitabine with radiation is an effective adjuvant therapy in ... CONCLUSION: Capecitabine with concurrent radiation was as effective as concurrent 5FU with radiation or fluoropyrimidine-based chemotherapy alone when used as ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2014.58.3930

Phase III Trial to Compare Adjuvant Chemotherapy With ... The Adjuvant Chemoradiotherapy in Stomach Tumors (ARTIST) trial tested whether the addition of radiotherapy to adjuvant chemotherapy improved disease-free ...

3. 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) versus 5-fluorouracil (5-FU), in combination with intravenous (IV) cisplatin, in ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0923753419460444

A phase II trial of capecitabine in previously untreated ... Despite overlapping confidence intervals, our objective response rate of 34% compares well with rates reported previously for other single agents in patients ...

5. ar.iiarjournals.org ar.iiarjournals.org/content/32/4/1397

Adjuvant Chemoradiation with 5-Fluorouracil or ... Results: The median follow up was 21 months. Five-years overall and disease-free survival were 44.5% and 48%, respectively. Eighteen patients experienced ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4394098/

Efficacy of S-1 vs capecitabine for the treatment of gastric cancer RESULTS: Compared with capecitabine regimens, the 1-year survival rate in gastric cancer patients was 0.80 (95%CI: 0.52-1.21, P = 0.29). The overall response ...

7. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.21986

Review of capecitabine as oral treatment of gastric ... Capecitabine is being investigated actively for the treatment of gastroesophageal cancer in the first-line metastatic and adjuvant settings.

8. ema.europa.eu ema.europa.eu/en/medicines/human/EPAR/xeloda

Xeloda | European Medicines Agency (EMA) Xeloda has been shown to be effective in treating colon, colorectal, gastric and breast cancer. The safety profile of the medicine is considered acceptable. ...