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

16 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment for gastroesophageal cancer?

Research shows that using docetaxel and 5-fluorouracil (5-FU) with radiotherapy is effective for esophageal cancer, with a high response rate and manageable side effects. This combination has shown favorable antitumor effects and good survival rates in patients with advanced esophageal cancer. ^{1 2 3 4 5}

Is the combination of immunotherapy and chemoradiotherapy safe for treating gastroesophageal cancer?

Studies have shown that chemoradiotherapy using docetaxel and 5-fluorouracil for esophageal cancer can be performed safely, with mild blood-related side effects and some non-blood-related side effects like esophagitis (inflammation of the esophagus) and anorexia (loss of appetite). No treatment-related deaths were reported, indicating a generally safe profile for this combination. ^{1 5 6 7 8}

What makes the Immunotherapy + Chemoradiotherapy treatment for gastroesophageal cancer unique?

This treatment combines immunotherapy (pembrolizumab) with chemoradiotherapy (docetaxel, fluorouracil, oxaliplatin, and radiation therapy), which is unique because it leverages the immune system to fight cancer while also using chemotherapy and radiation to directly target cancer cells. This combination aims to enhance the overall effectiveness against gastroesophageal cancer compared to traditional treatments that may not include immunotherapy. ^{1 4 9 10 11}

What is the purpose of this trial?

This phase I trial investigates how well pembrolizumab and chemoradiotherapy works in treating patients with gastroesophageal cancer that cannot be removed by surgery (unresectable). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as fluorouracil, oxaliplatin and docetaxel 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 photons to kill tumor cells and shrink tumors. Giving pembrolizumab together with chemoradiotherapy may help to control gastroesophageal cancer.

Research Team

Jaffer Ajani, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Results of Neoadjuvant Chemoradiotherapy With Docetaxel and 5-Fluorouracil Followed by Esophagectomy to Treat Locally Advanced Esophageal Cancer. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Comparing docetaxel plus cisplatin versus fluorouracil plus cisplatin in esophageal squamous cell carcinoma treated with neoadjuvant chemoradiotherapy. [2022]

3. Japan pubmed.ncbi.nlm.nih.gov

[Weekly docetaxel in combination with concomitant radiotherapy for esophageal cancer]. [2018]

4. Italy pubmed.ncbi.nlm.nih.gov

Weekly docetaxel with concomitant radiotherapy in patients with inoperable oesophageal cancer. [2022]

5. United States 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. [2022]

6. Canada pubmed.ncbi.nlm.nih.gov

A Pilot Study of Chemoradiotherapy With Weekly Docetaxel for Thoracic Esophageal Carcinoma With T4 and/or M1 Lymph Node Metastasis. [2022]

7. Switzerland 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. [2018]

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

Phase I study of docetaxel (TXT) and 5-fluorouracil (5-FU) with concurrent radiotherapy in patients with advanced esophageal cancer. [2018]

9. Greece pubmed.ncbi.nlm.nih.gov

Docetaxel/ TS-1 with radiation for unresectable squamous cell carcinoma of the esophagus--a phase II trial. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Preoperative pembrolizumab combined with chemoradiotherapy for oesophageal squamous cell carcinoma (PALACE-1). [2021]

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

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. [2023]