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

25 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase Ib trial investigates the side effects and how well a shorter course of chemotherapy and radiation treatment (chemoradiotherapy) for 2 weeks instead of 5 weeks followed by standard chemotherapy works in treating patients with gastric cancer who are scheduled to have treatment and then surgery to remove the tumor. Chemotherapy drugs, such as capecitabine and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy sources to kill tumor cells and shrink tumors. Giving short-course chemo-radiotherapy before chemotherapy and surgery may help to control the disease.

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.

What data supports the effectiveness of the drug Capecitabine (Xeloda) with radiation therapy for gastric cancer?

Research shows that Capecitabine, when combined with radiation therapy, is effective in treating gastric cancers, similar to the established use of 5-fluorouracil (5-FU) with radiation. Capecitabine is a convenient oral drug that acts as a radiosensitizer, enhancing the effects of radiation therapy in various gastrointestinal cancers, including gastric cancer. ^{1 2 3 4 5}

Is the combination of capecitabine and radiation therapy generally safe for humans?

Capecitabine, an oral form of chemotherapy, is generally considered safe and is preferred by many patients because it can be taken at home. It has a favorable safety profile, with common side effects including hand-foot syndrome (redness and swelling of the hands and feet), mouth sores, and diarrhea. Combining capecitabine with radiation therapy has shown promise in treating various cancers, with ongoing studies to further evaluate its safety and effectiveness. ^{2 4 6 7 8}

How does the treatment of Capecitabine with radiation therapy differ from other treatments for gastric cancer?

This treatment is unique because Capecitabine is an oral drug that is selectively activated in tumor tissues, making it more convenient and potentially more effective than the traditional 5-Fluorouracil (5-FU) infusion. It enhances the effect of radiation therapy by increasing the concentration of the active drug in cancer cells, which may improve treatment outcomes. ^{1 2 4 9 10}

Research Team

Brian Badgwell, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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]

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]

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]

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]

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]

References

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

Capecitabine with radiation is an effective adjuvant therapy in gastric cancers. [2021]

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

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

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

Phase II study of capecitabine (Xeloda) and concomitant boost radiotherapy in patients with locally advanced rectal cancer. [2022]

4. England pubmed.ncbi.nlm.nih.gov

A phase II trial of capecitabine in previously untreated patients with advanced and/or metastatic gastric cancer. [2022]

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

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

6. Scotland pubmed.ncbi.nlm.nih.gov

Development of and clinical experience with capecitabine (Xeloda) in the treatment of solid tumours. [2015]

7. United States 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. [2022]

8. Greece pubmed.ncbi.nlm.nih.gov

Irinotecan plus capecitabine as first-line chemotherapy in advanced colorectal cancer. [2018]

9. England pubmed.ncbi.nlm.nih.gov

S-1 for the treatment of gastrointestinal cancer. [2022]

10. Thailand pubmed.ncbi.nlm.nih.gov

Can capecitabine be used instead of concurrent bolus 5-FU in postoperative chemoradiotherapy for gastric adenocarcinoma? [2019]