What side effects are associated with this type of intervention?

Common treatments for esophageal cancer, such as pembrolizumab (a PD-1 inhibitor) combined with chemotherapy, are associated with several side effects. Pembrolizumab can cause immune-related adverse events, including pneumonitis, colitis, hepatitis, endocrinopathies, and skin reactions. Chemotherapy-related side effects often include nausea, vomiting, fatigue, neutropenia, anemia, and increased risk of infections. Both treatment modalities can lead to severe (grade 3 or higher) adverse events, but these are generally manageable with appropriate medical intervention.

What prior FDA approvals exist?

Pembrolizumab, a PD-1 inhibitor, has been approved by the FDA for the treatment of esophageal cancer, particularly for patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC) with high PD-L1 expression. The KEYNOTE-181 trial demonstrated its superiority over chemotherapy in second-line therapy, showing improved overall survival and fewer severe adverse events. Other PD-1 inhibitors, such as nivolumab, have also been explored in clinical trials for similar indications, but pembrolizumab remains a prominent option due to its established efficacy and safety profile.

What other types of research exist?

Promising alternatives to Pembrolizumab for esophageal cancer patients include Nivolumab, Avelumab, Camrelizumab, and Tislelizumab. These drugs have shown efficacy in clinical trials and are potential options for treatment in 2024.

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Checkpoint Inhibitor

Pembrolizumab + Chemotherapy for Esophageal Cancer

Phase 2

Waitlist Available

Led By Manish Shah, MD

Research Sponsored by Weill Medical College of Cornell University

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Clinical tumor stage should be T2 Npositive M0 or T3--T4, Nany, M0

Patients must have histologically or cytologically confirmed esophageal or GEJ adenocarcinoma

Must not have

Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)

Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment

Timeline

Screening 3 weeks

Treatment Varies

Follow Up until death from any cause or for a maximum of 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing if adding pembrolizumab to standard treatments can help patients with advanced esophageal cancer. Pembrolizumab boosts the immune system to better fight cancer. The goal is to see if this combination improves patient outcomes. Pembrolizumab has been used in various cancers, including melanoma, lung cancer, and head and neck cancer, showing durable responses and significant advancements in treatment options.

Who is the study for?

This trial is for adults over 18 with locally advanced esophageal adenocarcinoma, who haven't had prior cancer treatments for their current diagnosis. They must have certain blood cell counts and organ function levels, be willing to provide tissue samples, and agree to use birth control. Exclusions include active infections, other recent cancers except some skin or prostate cancers, autoimmune diseases needing treatment in the last 2 years, known HIV or hepatitis B/C.

What is being tested?

The study tests Pembrolizumab combined with chemotherapy (Taxol and Carboplatin) and chemoradiation on patients with esophageal adenocarcinoma. It's a phase II trial aiming to see how safe this combination is and how well it works by looking at disease-free survival after one year.

What are the potential side effects?

Pembrolizumab can cause immune system reactions that may affect organs like lungs or intestines; Taxol and Carboplatin might lead to low blood cell counts increasing infection risk, fatigue, hair loss, nerve damage causing numbness or tingling sensations.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My cancer is at a specific stage but hasn't spread to distant parts.

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My cancer is confirmed to be esophageal or GEJ adenocarcinoma.

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I am willing to give a tissue sample of my tumor during an endoscopy.

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I am eligible for surgery to remove my cancer.

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My kidney function, measured by creatinine or GFR, is within the normal range.

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I am 18 years old or older.

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I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have been diagnosed with HIV.

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I have an immune system disorder or have been on steroids or other immune-weakening medicines in the last week.

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I have or had lung inflammation not caused by an infection.

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I am currently being treated for an infection with medication.

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My cancer has spread to other parts of my body.

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I have been treated with drugs targeting PD-1, PD-L1, or PD-L2.

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I have received treatment like chemotherapy or radiation for esophageal cancer.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ until death from any cause or for a maximum of 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~until death from any cause or for a maximum of 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and until death from any cause or for a maximum of 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Number of Participants With Major Pathological Response

Secondary study objectives

Number of Participants That Remained Progression Free as of 1 Year

Overall Survival Rates

R0 Resection Rate.

Other study objectives

Association of Anti-PD1 Therapy With Increased Intra-tumoral Immune Cell Infiltration.

Improved 1 Year Survival

Induction of PD-L1 Expression or Induction of an Inflammatory Signature in Tumors.

+2 more

Side effects data

From 2024 Phase 3 trial • 804 Patients • NCT03040999

64%

Radiation skin injury

63%

Stomatitis

58%

Anaemia

56%

Nausea

48%

Dry mouth

45%

Constipation

45%

Weight decreased

44%

Dysphagia

42%

Neutrophil count decreased

33%

Dysgeusia

33%

Vomiting

32%

Fatigue

31%

White blood cell count decreased

28%

Hypomagnesaemia

26%

Decreased appetite

25%

Hypothyroidism

25%

Hypokalaemia

24%

Lymphocyte count decreased

24%

Platelet count decreased

23%

Oropharyngeal pain

23%

Blood creatinine increased

22%

Diarrhoea

22%

Odynophagia

20%

Hypoacusis

20%

Alanine aminotransferase increased

20%

Hyponatraemia

19%

Tinnitus

19%

Oral candidiasis

19%

Asthenia

16%

Pyrexia

16%

Cough

15%

Aspartate aminotransferase increased

15%

Rash

14%

Insomnia

13%

Acute kidney injury

13%

Pharyngeal inflammation

13%

Pruritus

12%

Dysphonia

12%

Gamma-glutamyltransferase increased

11%

Pneumonia

11%

Dehydration

10%

Hyperthyroidism

10%

Hypoalbuminaemia

10%

Hypocalcaemia

10%

Headache

10%

Productive cough

Neck pain

Peripheral sensory neuropathy

Gastrooesophageal reflux disease

Hiccups

Hyperglycaemia

Hyperuricaemia

Dizziness

Hypophosphataemia

Urinary tract infection

Ear pain

Localised oedema

Hyperkalaemia

Erythema

Oral pain

Abdominal pain upper

Arthralgia

Anxiety

Febrile neutropenia

Dyspepsia

Saliva altered

Back pain

Oedema peripheral

Hypertension

Dyspnoea

Nasopharyngitis

Alopecia

Dry skin

Sepsis

Pneumonia aspiration

Trismus

Pneumonitis

Laryngeal oedema

Malnutrition

Pharyngeal haemorrhage

Cellulitis

Septic shock

Clostridium difficile colitis

Systemic infection

Cardiac arrest

Death

Bronchitis

Hepatitis

Immune-mediated hepatitis

Oesophagitis

General physical health deterioration

Hypophagia

Tumour haemorrhage

Cerebrovascular accident

Syncope

Acute respiratory failure

Aspiration

Colitis

Mouth haemorrhage

Hypersensitivity

Acute myocardial infarction

Abscess neck

Device related infection

Stoma site infection

Vascular device infection

Wound infection

Hypercalcaemia

Pulmonary embolism

Respiratory failure

100%

80%

60%

40%

20%

Study treatment Arm

Placebo + CRT Followed by Placebo

Pembrolizumab + CRT Followed by Pembrolizumab

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Cohort 2Experimental Treatment3 Interventions

Subjects in Cohort 2 receive pembrolizumab along with induction chemotherapy with taxol/ carboplatin followed by weekly chemoradiation (taxol/ carboplatin) with pembrolizumab. Following surgery, pembrolizumab is administered every 3 weeks for 1 year. Pembrolizumab dosing is 200 mg administered as a 30 minute IV infusion.

Group II: Cohort 1Experimental Treatment3 Interventions

Subjects in Cohort 1 receive conventional induction chemotherapy with taxol/ carboplatin followed by weekly chemoradiation (taxol/ carboplatin) with pembrolizumab. Following surgery, pembrolizumab is administered every 3 weeks for 1 year. Pembrolizumab dosing is 200 mg administered as a 30 minute IV infusion.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Taxol

2001

Completed Phase 3

~3310

Carboplatin

2014

Completed Phase 3

~6120

Pembrolizumab

2017

Completed Phase 3

~2810

0 / 14Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for esophageal cancer include chemotherapy, chemoradiation, and immune checkpoint inhibitors like pembrolizumab. Chemotherapy uses drugs to kill rapidly dividing cancer cells, while chemoradiation combines chemotherapy with radiation therapy to enhance the cancer-killing effects. Pembrolizumab, a PD-1 inhibitor, works by blocking the PD-1 pathway, which cancer cells exploit to evade the immune system. By inhibiting this pathway, pembrolizumab helps the immune system recognize and attack cancer cells more effectively. These treatments are crucial for esophageal cancer patients as they offer different mechanisms to target and destroy cancer cells, potentially improving survival rates and quality of life.