Immunotherapy + Chemoradiotherapy for Gastroesophageal Cancer

Overseen By Jaffer A Ajani

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Cardiovascular impairment, Pneumonitis, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: 39

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining immunotherapy and chemoradiotherapy can treat gastroesophageal cancer that surgery cannot remove. It uses pembrolizumab, an immunotherapy designed to boost the body's immune system to fight cancer, alongside chemotherapy and radiation. Individuals with confirmed gastroesophageal cancer who cannot undergo surgery, or choose not to, may be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative combination therapy.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive therapy or have received certain treatments like live vaccines recently, you may not be eligible. It's best to discuss your specific medications with the trial team.

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

Research has shown that pembrolizumab, when combined with chemotherapy, is generally well-tolerated. In earlier studies, most patients experienced some side effects, but these were usually manageable. Specifically, about 95% of patients experienced side effects, but only around 59% had more serious ones. This indicates that while side effects are common, severe issues occur less frequently.

When combined with chemoradiotherapy, pembrolizumab has shown promising results in patients with advanced esophageal cancers that are difficult to treat. These studies suggest that the treatment could be effective for those with gastroesophageal cancer that cannot be surgically removed.

Overall, while side effects can occur, many patients tolerate the treatment well. It is important to discuss any concerns with a healthcare provider to understand what this means for a specific situation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about this treatment for gastroesophageal cancer because it combines pembrolizumab, an immunotherapy drug, with chemoradiotherapy. Pembrolizumab works by activating the immune system to better recognize and attack cancer cells, which is different from the traditional chemoradiotherapy approach that directly targets cancer cells with drugs and radiation. This combination has the potential to enhance the overall effectiveness of treatment by leveraging the body's own defenses alongside standard therapies. This new approach could offer improved outcomes for patients by potentially increasing survival rates and decreasing recurrence compared to existing treatments.

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

In this trial, participants will receive a combination of pembrolizumab with chemoradiotherapy. Research has shown that pembrolizumab with chemotherapy can help people with stomach and esophageal cancer live longer and respond better to treatment. Studies have found that this combination significantly improves survival and cancer response. Docetaxel, one of the chemotherapy drugs in this trial, has shown good results, with studies reporting it effectively controls gastric cancer. Fluorouracil, another chemotherapy drug used in this trial, works by slowing cancer cell growth, although resistance can develop. Oxaliplatin, often used with other treatments, has shown positive results in trials. Radiation therapy, which uses high-energy rays to kill cancer cells, has been effective in extending patient survival and preventing cancer spread in the digestive system. By combining these treatments, the goal is to better manage gastroesophageal cancer by attacking it in different ways. ^{6 7 8 9 10}

Who Is on the Research Team?

Jaffer Ajani, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced gastroesophageal cancer that can't be removed by surgery. They should have a good performance status, meaning they're fairly active and able to care for themselves. Participants must not be pregnant or breastfeeding, agree to use contraception, and have adequate organ function as shown by specific blood tests.

Inclusion Criteria

My brain cancer has not worsened recently.

My cancer in the stomach or esophagus cannot be removed by surgery.

My blood clotting tests are normal or within the treatment range if I'm on blood thinners.

Exclusion Criteria

I have an autoimmune disease treated with medication in the last 2 years.

I have been treated with specific immune therapy drugs before.

Note: Participants who have entered the follow-up phase of an investigational trial may participate as long as it has been 4 weeks after the last dose of the previous investigational agent

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Chemotherapy

Participants receive pembrolizumab and oxaliplatin with fluorouracil for 8 weeks

8 weeks

Pembrolizumab every 3 weeks, Oxaliplatin and Fluorouracil every 2 weeks

Consolidation Chemoradiation

Participants receive pembrolizumab, fluorouracil, docetaxel, and radiation therapy

5 weeks

Pembrolizumab every 3 weeks, Fluorouracil continuous, Docetaxel weekly, Radiation therapy 28 fractions

Maintenance Treatment

Participants continue pembrolizumab treatment for up to 30 cycles

Up to 90 weeks

Pembrolizumab every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Follow-up at 30 days, then every 9-12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Docetaxel
• Fluorouracil
• Oxaliplatin
• Pembrolizumab
• Radiation Therapy

Trial Overview The study is testing the combination of pembrolizumab (an immune system-boosting drug) with chemoradiotherapy (a mix of chemotherapy drugs and radiation therapy). The goal is to see if this combo is better at controlling gastroesophageal cancer compared to standard treatments.

How Is the Trial Designed?

Group I: Treatment (pembrolizumab, chemoradiotherapy) Experimental Treatment 5 Interventions

See Detailed Description

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

Approved in United States as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in European Union as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Canada as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Japan as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate 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

Preoperative treatment with pembrolizumab combined with chemoradiotherapy was found to be safe for 20 patients with resectable esophageal squamous cell carcinoma, with a high pathologic complete response (pCR) rate of 55.6%.

Despite some patients experiencing significant adverse events, including grade III lymphopenia in 65% of cases, the treatment did not delay surgery, indicating its feasibility for clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative pembrolizumab combined with chemoradiotherapy for oesophageal squamous cell carcinoma (PALACE-1). Li, C., Zhao, S., Zheng, Y., 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]

In a study of 124 patients with advanced or recurrent esophageal cancer who had previously received platinum-based chemotherapy, paclitaxel (PTX) showed higher objective response rates (25.7% vs. 10.3%) and disease control rates (60.0% vs. 34.6%) compared to docetaxel (DTX).

While both treatments had similar overall survival rates (6.1 months for DTX vs. 7.2 months for PTX), PTX was associated with fewer severe side effects, such as grade 3-4 neutropenia (21.1% for PTX vs. 48.8% for DTX) and febrile neutropenia (5.3% for PTX vs. 20.9% for DTX), making it a more feasible option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective comparison of docetaxel and paclitaxel for patients with advanced or recurrent esophageal cancer who previously received platinum-based chemotherapy. Mizota, A., Shitara, K., Kondo, C., et al.[2018]

In a study of 38 patients with locally advanced esophageal cancer, neoadjuvant chemoradiotherapy (CRT) using docetaxel and 5-fluorouracil showed low toxicity, with esophagitis being the most common side effect (26.3% grade 3), and no postoperative mortality reported.

The treatment resulted in favorable surgical outcomes, with 92.1% of patients achieving complete resection and a 5-year overall survival rate of 44.7%, indicating that this regimen is a promising alternative for patients who cannot tolerate traditional platinum-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of Neoadjuvant Chemoradiotherapy With Docetaxel and 5-Fluorouracil Followed by Esophagectomy to Treat Locally Advanced Esophageal Cancer. Hamai, Y., Hihara, J., Emi, M., et al.[2018]

In a phase II study involving 16 patients with inoperable locally advanced esophageal squamous cell carcinoma, the chemoradiotherapy regimen using docetaxel and 5-fluorouracil showed a high response rate of 94%, with 31% achieving complete response.

The treatment was found to be safe, with mild hematologic toxicity and manageable nonhematologic side effects, leading to a median progression-free survival of 20 months and 3-year and 5-year survival rates of 44% and 31%, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of definitive chemoradiotherapy using docetaxel and 5-fluorouracil in patients with unresectable locally advanced esophageal squamous cell carcinoma: a phase II study. Hihara, J., Hamai, Y., Emi, M., et al.[2022]

Citations

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Addition of docetaxel to S-1 results in significantly superior ... Five-year RFS rates were 59.78% in the S-1 plus docetaxel group and 50.63% in the S-1 group (HR 0.726, 95%CI 0.599–0.879; p = 0.0010). Five-year ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.4_suppl.333

Efficacy and safety of albumin-bound docetaxel vs. ... Median overall survival was 11.3 months with HB1801 versus 7.8 months with docetaxel (HR = 0.59 [95%CI 0.35, 1.01], p=0.025). Treatment-related ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2621422/

Review of docetaxel in the treatment of gastric cancer - PMC In 42 evaluable patients, ORR rate was 40.5% (1 complete response), and an additional 38.1% had stable disease as their best response. With 75% of the patients ...

4. cancernetwork.com cancernetwork.com/view/docetaxel-gastric-and-esophageal-carcinomas

Docetaxel for Gastric and Esophageal Carcinomas Docetaxel demonstrated a cytotoxic effect in 10 of the 18 clinical specimens (56%)-an effectiveness rate similar to that of cisplatin (50%) on the same ...

5. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(25)00154-8/fulltext?rss=yes

Docetaxel as part of first-line chemotherapy for gastric ... Overall survival was also superior for TFOX (median 15·08 months [13·70–16·72] vs 12·65 months [10·94–14·00]), as was objective response rate ( ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11908035/

Efficacy and safety of pembrolizumab in advanced gastric and ... Pembrolizumab combined with chemotherapy significantly improved OS (MD = 1.92 months; 95% CI: 0.94 to 2.91) and ORR (MD = 11.05%; 95% CI: 6.29 ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7927908/

KEYNOTE-975 study design: a Phase III study of definitive ... Pembrolizumab is well tolerated and provides promising antitumor activity in patients with previously treated, advanced, unresectable esophageal ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.4036

KEYNOTE-859: 4.5-year median follow-up of ... Treatment-related AEs were reported in 751 pts (95.7%; grade 3-5, 466 [59.4%]) for pembro + chemo and 736 (93.5%; grade 3-5, 404 [51.3%]) for ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT03382600

Safety and Efficacy of Pembrolizumab (MK-3475) in ... The purpose of this study is to estimate objective response rates (ORRs) of pembrolizumab + oxaliplatin + TS-1 and pembrolizumab + cisplatin + TS-1, ...

10. ascopubs.org ascopubs.org/doi/10.1200/JCO.20.01888

Randomized Phase III KEYNOTE-181 Study of ... More patients had durable responses with pembrolizumab versus chemotherapy, with 53.5% versus 38.1% of patients, respectively, estimated to have ...