Pembrolizumab + Capecitabine + Radiation for Gastric Cancer

Not currently recruiting at 4 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Rutgers, The State University of New Jersey

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Metastatic disease, Active infection, 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: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of combining pembrolizumab, capecitabine, and radiation therapy for treating a specific type of stomach cancer, particularly in patients with mismatch repair deficiencies or Epstein-Barr virus-positive tumors. Pembrolizumab, a monoclonal antibody, may help stop tumor cell growth, while capecitabine, a chemotherapy drug, works to kill or inhibit the spread of cancer cells. Radiation therapy uses powerful x-rays to shrink tumors. This trial suits individuals with operable stomach cancer that has not spread and whose tumors are either mismatch repair deficient or Epstein-Barr virus positive. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant medical advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy or any immunosuppressive therapy, you must stop these at least 7 days before starting the trial treatment.

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

Research has shown that the combination of pembrolizumab, capecitabine, and radiation therapy has been tested primarily for advanced stomach cancers. Pembrolizumab, a monoclonal antibody, has received FDA approval for certain stomach cancers, indicating its safety for these conditions is well understood.

In earlier studies, patients who received pembrolizumab with treatments like chemotherapy often experienced side effects such as tiredness, nausea, and weakness. Capecitabine, a chemotherapy drug used for various cancers, is usually well-tolerated. Radiation therapy, which uses high-energy rays to treat cancer, commonly causes side effects like skin irritation and fatigue.

Overall, while each treatment has typical side effects, they are generally manageable. Potential trial participants should consult their doctors to understand what to expect and how to handle these effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this combination treatment for gastric cancer because it brings together pembrolizumab, an immunotherapy drug, with capecitabine, a chemotherapy agent, and radiation therapy. Unlike traditional treatments that primarily focus on chemotherapy alone, this approach leverages pembrolizumab to harness the body’s immune system to target cancer cells more effectively. The integration of immunotherapy with chemotherapy and radiation could potentially enhance the overall effectiveness, offering a more comprehensive attack on cancer cells. Moreover, the use of pembrolizumab might reduce the reliance on chemotherapy, potentially leading to fewer side effects for patients. This innovative combination aims to improve outcomes and quality of life for those battling gastric cancer.

What evidence suggests that pembrolizumab, capecitabine, and radiation therapy might be effective for gastric cancer?

This trial will evaluate the combination of pembrolizumab, capecitabine, and radiation therapy for treating stomach cancer. Studies have shown that combining these treatments can be effective. Pembrolizumab blocks a protein called PD-1, which cancer cells use to hide from the immune system, allowing the immune system to attack the cancer. Capecitabine, a chemotherapy drug, stops cancer cells from growing and dividing. Radiation therapy uses high-energy rays to kill cancer cells and shrink tumors. Research suggests that this combination may improve outcomes for patients with certain types of stomach cancer, specifically those with mismatch repair deficiency and Epstein-Barr virus positivity, by attacking the cancer in multiple ways. Early results indicate that this approach could be more effective than using these treatments individually. ^{1 3 6 7 8}

Who Is on the Research Team?

Salma Jabbour, MD

Principal Investigator

Rutgers Cancer Institute of New Jersey

Are You a Good Fit for This Trial?

This trial is for adults with operable gastric cancer that's mismatch repair deficient or Epstein-Barr virus positive. They must have certain blood and organ function levels, not be pregnant or breastfeeding, agree to use contraception, and have no history of specific treatments or conditions that could affect the trial.

Inclusion Criteria

I am a man who can father a child and agree to use birth control.

Meet specified hematologic and biochemical parameters

I've had recent scans and tests to check my cancer's stage.

Exclusion Criteria

I have not taken steroids or immunosuppressants in the last week.

I have had pneumonitis treated with steroids or have it now.

Active autoimmune disease requiring systemic treatment in the past 2 years

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preoperative Treatment

Participants receive pembrolizumab intravenously every 21 days for up to 2 courses, followed by surgery within 2-6 weeks

6-10 weeks

Postoperative Chemoradiation

Participants receive pembrolizumab and capecitabine, with radiation therapy starting from course 4, for up to 5 weeks

15-20 weeks

Maintenance Treatment

Participants continue to receive pembrolizumab every 21 days for up to 11 courses

33 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Capecitabine
• Pembrolizumab
• Radiation Therapy

Trial Overview The study tests pembrolizumab (a monoclonal antibody) combined with capecitabine (chemotherapy) and radiation therapy. It aims to see if this combination is more effective in stopping the growth of tumor cells compared to current standard treatments.

How Is the Trial Designed?

Group I: Treatment (pembrolizumab, capecitabine, radiation therapy) Experimental Treatment 4 Interventions

Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. Within 2-6 weeks, patients undergo surgery. Beginning up to 56 days after surgery, patients receive pembrolizumab IV over 30 minutes on day 1 and capecitabine PO BID on days 1-14. Treatment repeats every 21 days for up to 5 courses in the absence of disease progression or unacceptable toxicity. Within 2-6 weeks of resting, patients continue to receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 11 courses in the absence of disease progression or unacceptable toxicity. Beginning course 4, patients undergo radiation therapy over 15-30 minutes on days 1-5 for up to 5 weeks.

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?

Rutgers, The State University of New Jersey

Lead Sponsor

Trials

471

Recruited

81,700+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

A retrospective study of 12 patients with severe renal impairment (GFR <30 mL/min) showed that capecitabine can be safely administered with close monitoring and dose adjustments, despite previous contraindications from the manufacturer based on a small Phase II trial.

Most patients experienced only mild to moderate adverse effects, and some showed a positive response to treatment, indicating that capecitabine may still be effective in this population when managed carefully.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective observational study on the use of capecitabine in patients with severe renal impairment (GFR Jhaveri, KD., Flombaum, C., Shah, M., 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]

Pembrolizumab (KEYTRUDA®) has shown efficacy and safety in treating recurrent high microsatellite instability (MSI-high) gastric cancer, as demonstrated in the KEYNOTE-158 and 061 trials.

In a case study of an elderly patient with recurrent gastric cancer after surgery, pembrolizumab was successfully used as a second-line treatment, suggesting it can be a viable option for older patients in late-line chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Long-Term Elderly Survivor with Recurrent MSI-High Gastric Cancer Using Pembrolizumab as a Second-Line Chemotherapy]. Hamada, S., Komatsu, S., Nishiko, M., et al.[2022]

Pembrolizumab (Keytruda) is approved for treating advanced endometrial carcinoma that is microsatellite instability-high or mismatch repair deficient, specifically for patients whose disease has progressed after previous treatments.

This approval is significant for patients who are not candidates for curative surgery or radiation, providing a new therapeutic option for a challenging stage of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Approved Use for Keytruda. Aschenbrenner, DS.[2022]

Capecitabine (Xeloda) is an effective treatment for advanced/metastatic breast cancer, showing a response rate of 20% in a phase 2 trial with a median survival time of 452 days for patients who were resistant to previous therapies.

The most common side effects reported were hand-foot syndrome and various blood-related issues, indicating that while Capecitabine can be beneficial, it also carries a risk of significant adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological and clinical properties of Xeloda (Capecitabine), a new oral active derivative of fluoropyrimidine. Nishida, M.[2018]

In a study of 45 patients with locally advanced rectal cancer, preoperative chemoradiation using capecitabine resulted in significant tumor downstaging, with 63% of primary tumors and 90% of lymph nodes showing downstaging, and a pathologic complete response in 31% of patients.

The treatment was found to be safe and well-tolerated, with no severe hematologic toxicities and manageable Grade 3 side effects, suggesting that capecitabine can effectively enhance surgical options, including sphincter-preserving surgeries for tumors near the anal verge.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative chemoradiation using oral capecitabine in locally advanced rectal cancer. Kim, JS., Kim, JS., Cho, MJ., et al.[2022]

Pembrolizumab (Keytruda) received FDA accelerated approval for treating recurrent gastric or gastroesophageal junction adenocarcinoma in patients whose tumors express PD-L1, based on a multicenter trial involving 259 patients, showing a 13.3% overall response rate.

The treatment was associated with common side effects like fatigue and decreased appetite, and serious adverse reactions included pneumonia and pulmonary embolism, highlighting the need for careful patient monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Recurrent Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma Expressing PD-L1. Fashoyin-Aje, L., Donoghue, M., Chen, H., et al.[2021]

Pembrolizumab (Keytruda) is an approved treatment for metastatic or locally advanced esophageal and gastroesophageal junction cancer, indicating its efficacy in targeting these specific cancer types.

It is used in combination with platinum- and fluoropyrimidine-based chemotherapy, suggesting a synergistic approach to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. Aschenbrenner, DS.[2023]

The combination of pembrolizumab, hypofractionated stereotactic irradiation (HFSRT), and bevacizumab was found to be generally safe and well tolerated in 32 patients with recurrent high-grade gliomas, with manageable treatment-related adverse events such as proteinuria and fatigue.

In the bevacizumab-naïve group, 83% of patients showed a complete or partial response, with a median overall survival of 13.45 months, indicating promising preliminary efficacy of this treatment combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated stereotactic re-irradiation with pembrolizumab and bevacizumab in patients with recurrent high-grade gliomas: results from a phase I study. Sahebjam, S., Forsyth, PA., Tran, ND., et al.[2021]

In a study of 19 colorectal cancer patients, capecitabine was shown to preferentially convert to 5-fluorouracil (5-FU) in tumor tissues, with 5-FU concentrations in tumors being 3.2 times higher than in adjacent healthy tissues, indicating effective targeting of the drug.

The enzyme thymidine phosphorylase (TP) plays a crucial role in this preferential activation, being significantly more active in colorectal tumors compared to healthy tissue, which helps explain the enhanced efficacy of capecitabine in treating colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preferential activation of capecitabine in tumor following oral administration to colorectal cancer patients. Schüller, J., Cassidy, J., Dumont, E., et al.[2022]

In a study of 14 patients with metastatic gastroesophageal cancer, combining palliative radiation therapy with the PD-1 inhibitor pembrolizumab resulted in an objective response rate of 28.6%, indicating potential effectiveness in this challenging cancer type.

While the combination therapy showed promising durable responses, the study did not find significant changes in PD-L1 expression that could explain the observed effects, suggesting that further research is needed to identify other biomarkers that may predict patient benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 2 Trial Combining Pembrolizumab and Palliative Radiation Therapy in Gastroesophageal Cancer to Augment Abscopal Immune Responses. Chao, J., He, TF., D'Apuzzo, M., et al.[2022]

A 74-year-old woman with lung adenocarcinoma developed fatal immune thrombocytopenia after receiving pembrolizumab following radiotherapy, highlighting a potential risk of severe immune-related adverse events (irAEs) when combining these treatments.

Flow cytometry analysis showed increased PD-1 and Ki-67 expression in T cells post-radiotherapy, suggesting that radiotherapy may enhance immune activation and contribute to the development of irAEs in patients undergoing anti-PD-1 therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab-related Immune Thrombocytopenia in a Patient with Lung Adenocarcinoma Treated by Radiotherapy: Potential Immune-related Adverse Event Elicited by Radiation Therapy. Tamanoi, D., Saruwatari, K., Imamura, K., et al.[2022]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

Citations

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Pembrolizumab, Capecitabine, and Radiation Therapy in ... This phase II trial studies how well pembrolizumab works with capecitabine and radiation therapy in treating patients with mismatch repair deficient and ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03221426

NCT03221426 | Study of Pembrolizumab (MK-3475) Plus ... The purpose of this study is to evaluate the efficacy of pembrolizumab (MK-3745) in the neoadjuvant (prior to surgery) or adjuvant (after surgery) treatment.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5827797/

Pembrolizumab for treatment of advanced gastric and ... Pembrolizumab is a monoclonal antibody directed against PD-1 that is US FDA approved for treatment of advanced PD-L1 positive gastric and gastroesophageal ...

4. withpower.com withpower.com/trial/phase-3-stomach-neoplasms-8-2017-38a01

Pembrolizumab + Capecitabine + Radiation for Gastric ... This phase II trial studies how well pembrolizumab works with capecitabine and radiation therapy in treating patients with mismatch repair deficient and ...

5. merck.com merck.com/news/mercks-keytruda-pembrolizumab-plus-chemotherapy-significantly-improved-overall-survival-versus-chemotherapy-alone-in-patients-with-her2-negative-gastric-or-gastroesophageal-junction/

Merck's KEYTRUDA® (pembrolizumab) Plus ... The five-year survival rate for patients diagnosed with gastric cancer at an advanced stage is only 6%. About KEYTRUDA® (pembrolizumab) injection, 100 mg.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03342937

KeyLargo: Pembrolizumab + Oxaliplatin + Capecitabine in ... Five (5) subjects will be enrolled and their safety data after 21 days of treatment will be reviewed before additional subjects are enrolled. Subjects on this ...

7. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-her2-positive-gastric-or-gastroesophageal-junction-adenocarcinoma

FDA approves pembrolizumab for HER2 positive gastric or ... FDA approves pembrolizumab for HER2 positive gastric or gastroesophageal junction adenocarcinoma expressing PD-L1 (CPS ≥1) · Efficacy and Safety.

8. keytruda.com keytruda.com/gastric-cancer/

adults with advanced stomach cancer Common side effects of KEYTRUDA when given with certain chemotherapy or chemotherapy with radiation therapy medicines include feeling tired or weak; nausea ...