Chemoradiation + Pembrolizumab/Lenvatinib for Esophageal Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Must not be taking: Immune checkpoint inhibitors, Multi-tyrosine kinase inhibitors

Disqualifiers: Active autoimmune disease, Brain metastasis, 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 tests a combination of treatments for esophageal cancer that hasn't spread beyond the esophagus. It examines the effectiveness of chemoradiation (a mix of chemotherapy and radiation) with the drugs pembrolizumab and lenvatinib in shrinking tumors before surgery. Pembrolizumab is an immunotherapy that aids the immune system in fighting cancer, while lenvatinib slows cancer cell growth. Individuals with non-metastatic esophageal cancer, including squamous cell or adenocarcinoma types, who are suitable for treatments like surgery, might be a good fit for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on certain treatments like immune checkpoint inhibitors, multi-tyrosine kinase inhibitors, or chronic systemic steroids. It's best to discuss your specific medications with the study team.

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

Research has shown that the combination of carboplatin and paclitaxel is usually well-tolerated. Although some patients in a study experienced serious side effects, the treatment proved effective for many. This suggests that most people's bodies can handle these drugs, but there remains a risk of significant side effects.

For pembrolizumab, studies with esophageal cancer patients indicate that the side effects are similar to those of other cancer treatments. While risks exist, they are generally expected and manageable.

Lenvatinib has been tested in many patients with various types of tumors. Although it can cause side effects, it is considered safe enough for use in many cancer treatments. Patients should be aware that side effects can occur but are usually known and manageable.

Overall, each treatment in this trial has been shown to be safe enough in previous studies and treatments. However, as with any treatment, potential side effects exist, so discussing these with the trial team is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of chemoradiation with pembrolizumab and lenvatinib for esophageal cancer because it introduces a novel approach by integrating immunotherapy and targeted therapy. Pembrolizumab is an immune checkpoint inhibitor that empowers the immune system to attack cancer cells more effectively, while lenvatinib is a targeted therapy that inhibits tumor blood vessel growth, potentially enhancing the effects of pembrolizumab. This combination could offer a more robust response compared to standard treatments like chemotherapy and radiation alone, providing a new avenue for patients with esophageal cancer to achieve better outcomes.

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

In this trial, participants will receive a combination of chemoradiation with pembrolizumab and lenvatinib to treat esophageal cancer. Research has shown that combining chemoradiation, which uses the drugs carboplatin and paclitaxel, with pembrolizumab can help patients live longer by effectively stopping tumor growth before surgery. Studies have found that adding pembrolizumab to chemotherapy reduces the risk of cancer worsening compared to chemotherapy alone. Lenvatinib, when used with pembrolizumab, has shown potential in fighting tumors, but its effect on survival rates in esophageal cancer remains under investigation. These treatments work together to shrink tumors and aim to improve patient outcomes. ^{6 7 8 9 10}

Who Is on the Research Team?

Vincent Chung, MD

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

Adults with non-metastatic esophageal or gastroesophageal junction cancer suitable for chemoradiation and surgery. Participants must have certain blood cell levels, organ function within specific limits, and agree to use birth control. Excluded are those with recent other treatments, immune conditions, severe allergies to similar drugs, active infections like HIV or hepatitis B/C, pregnant/breastfeeding women, and anyone unlikely to follow the study plan.

Inclusion Criteria

I have received a specific dose of radiation therapy.

Exceptions may be granted only with study principal investigator (PI) approval if archival tissue is unavailable

Documented informed consent of the participant and/or legally authorized representative

Exclusion Criteria

I have not had radiotherapy in the last 21 days.

I have an active case of tuberculosis.

I have not been treated with immune checkpoint inhibitors.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemoradiation

Patients receive carboplatin and paclitaxel intravenously once a week and undergo external beam radiation therapy over 6 weeks. Pembrolizumab is administered on day 1 of radiation therapy.

6 weeks

Window Period

Patients receive pembrolizumab intravenously on day 1 of week 3 and lenvatinib mesylate orally once daily from weeks 3 to 6.

4 weeks

Surgery/Surveillance

Patients without complete response undergo standard surgical resection. Patients with complete response undergo surveillance via periodic endoscopic biopsy.

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin, Paclitaxel
• Endoscopic Biopsy
• External Beam Radiation Therapy
• Lenvatinib Mesylate
• Pembrolizumab
• Resection

Trial Overview The trial is testing if a combination of chemoradiation (carboplatin/paclitaxel) and immunotherapy drug pembrolizumab followed by pembrolizumab plus anti-cancer drug lenvatinib before surgery can effectively treat patients. The goal is to see if this regimen kills more tumor cells compared to current standard treatments.

How Is the Trial Designed?

Group I: Treatment (chemoradiation, pembrolizumab, lenvatinib) Experimental Treatment 7 Interventions

CHEMORADIATION PHASE: Patients receive carboplatin IV and paclitaxel IV QW for up to 6 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo EBRT over 6 weeks and receive pembrolizumab IV over 30 minutes on day 1 of radiation therapy in the absence of disease progression or unacceptable toxicity. WINDOW PERIOD: Patients receive pembrolizumab IV over 30 minutes on day 1 of week 3 and lenvatinib mesylate PO QD at weeks 3-6 in the absence of disease progression or unacceptable toxicity. SURGERY/SURVEILLANCE: Patients without complete response undergo standard of care surgical resection. Patients with complete response/pursue non-operative management undergo surveillance via periodic endoscopic biopsy.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 39 patients with locally advanced esophageal squamous cell carcinoma (ESCC), pembrolizumab combined with neoadjuvant chemotherapy resulted in a high objective response rate of 87.2% and a disease control rate of 100%.

The treatment led to significant surgical outcomes, with a major pathological response rate of 68.2% and a complete pathological response rate of 45.5% among those who underwent radical surgery, while maintaining a manageable safety profile with only 15.4% experiencing severe adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab combined with paclitaxel and platinum as induction therapy for locally advanced esophageal squamous cell carcinoma: a retrospective, single-center, three-arm study. Lin, W., Huang, Y., Zhu, L., et al.[2023]

In a study of 55 patients with locally advanced or metastatic esophageal squamous cell carcinoma (ESCC), pembrolizumab combined with chemotherapy or radiotherapy showed favorable long-term survival outcomes, with a 12-month overall survival rate of 78.8%.

The treatment was found to be safe and manageable, with long-term adverse effects reported in only a small number of patients, indicating that pembrolizumab is a promising option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term efficacy and predictors of pembrolizumab-based regimens in patients with advanced esophageal cancer in the real world. Wang, HC., Huang, X., Chen, J., et al.[2023]

Pembrolizumab, a monoclonal antibody that inhibits PD-1, shows significant survival benefits for patients with metastatic or recurrent esophageal cancer who have a PD-L1 CPS ≥10 when used as a second-line treatment.

Current research is exploring the effectiveness of combining pembrolizumab with other treatments, which may enhance outcomes for patients with esophageal squamous cell carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of esophageal cancer. Yamamoto, S., Kato, K.[2021]

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]

The KEYNOTE-975 trial is a Phase III study designed to evaluate the effectiveness of pembrolizumab combined with chemoradiotherapy as a first-line treatment for patients with locally advanced, unresectable esophageal or gastroesophageal junction cancer.

This trial aims to improve survival outcomes, as current treatments have poor results, and will measure overall survival and event-free survival as its primary endpoints.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

KEYNOTE-975 study design: a Phase III study of definitive chemoradiotherapy plus pembrolizumab in patients with esophageal carcinoma. Shah, MA., Bennouna, J., Doi, T., 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]

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