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Fluoropyrimidine-based Chemotherapy

Pembrolizumab + Lenvatinib + Chemo for Esophageal Cancer

Phase 3
Recruiting
Research Sponsored by Merck Sharp & Dohme Corp.
Eligibility Criteria Checklist
Specific guidelines that determine who can or cannot participate in a clinical trial
Must have
Has adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP≤150/90 millimeters of mercury (mm Hg) with no change in antihypertensive medications within 1 week prior to randomization
Has a histologically or cytologically confirmed diagnosis of metastatic squamous cell carcinoma of the esophagus
Must not have
Has had previous therapy for locally advanced unresectable or metastatic esophageal cancer
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
Timeline
Screening 3 weeks
Treatment Varies
Follow Up up to ~51 months
Awards & highlights

Summary

This trial is meant to compare the effects of two different cancer treatments on patients with metastatic esophageal cancer. The first treatment is pembrolizumab plus lenvatinib plus chemotherapy, and the second treatment is pembrolizumab plus chemotherapy. The study will measure overall survival and progression-free survival to see which treatment is more effective.

Who is the study for?
This trial is for adults with metastatic squamous cell carcinoma of the esophagus. Participants must have controlled blood pressure, adequate organ function, and agree to contraception if applicable. Exclusions include adenocarcinoma of the esophagus, significant bleeding risks, recent major surgery or radiotherapy, active infections like Hepatitis B/C or HIV, weight loss over 20% in last 3 months, and certain cardiovascular diseases.Check my eligibility
What is being tested?
The study tests pembrolizumab plus lenvatinib with chemotherapy against pembrolizumab with chemotherapy alone in first-line treatment for metastatic esophageal cancer. The goal is to see which combination improves overall survival (OS) and progression-free survival (PFS) better.See study design
What are the potential side effects?
Potential side effects may include allergic reactions to drugs used; high blood pressure from lenvatinib; immune-related issues such as inflammation in organs due to pembrolizumab; fatigue; digestive problems; increased risk of infection; and possible nerve damage.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below
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My blood pressure is 150/90 or lower, and my medication hasn't changed in the last week.
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My esophageal cancer is confirmed to be squamous cell and has spread.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:
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I have received treatment for advanced esophageal cancer that cannot be surgically removed.
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I have cancer that has spread to my brain or spinal cord.
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I have had serious heart problems in the last year.
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My cancer, which started in the esophagus, has spread to other parts of my body.
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I have trouble swallowing or an obstruction in my digestive tract.
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I have a history of Hepatitis B or an active Hepatitis C infection.
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I frequently need treatment for fluid buildup in my chest or abdomen.
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I have lost more than 20% of my weight in the last 3 months.
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I have another cancer that is getting worse or was treated in the last 3 years.
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My cancer has spread to nearby organs like the aorta or windpipe.
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I have frequent and uncontrollable diarrhea.
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My scans show my tumor is surrounding a major blood vessel or has holes.
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I am at risk for or have had significant GI bleeding.
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I have an immune system disorder, am on long-term steroids, or have had an organ transplant.
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I have had lung inflammation not caused by infection, treated with steroids.
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My cancer is in the esophagus and has not spread far.
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I have not had radiotherapy in the last 2 weeks or suffered from radiation pneumonitis.
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I have moderate to severe numbness, tingling, or pain in my hands or feet.
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I have an autoimmune disease but haven't needed strong medication for it in the last 2 years.

Timeline

Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~up to ~51 months
This trial's timeline: 3 weeks for screening, Varies for treatment, and up to ~51 months for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.
Primary outcome measures
Part 1 (FP and TP Safety Run-in): Number of Participants With Adverse Events (AEs)
Part 1 (FP and TP Safety Run-in): Number of Participants With Dose Limiting Toxicities (DLTs)
Part 1 (FP and TP Safety Run-in): Number of Participants who Discontinued Study Treatment Due to an AE
+2 more
Secondary outcome measures
Part 2 (Main Study): Change From Baseline in HRQoL Score Using EORTC Quality of Life Questionnaire-Oesophageal Module (QLQ-OES18)
Part 2 (Main Study): Change From Baseline in Health-related Quality of life (HRQoL) Score Using European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30)
Part 2 (Main Study): DOR per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 CPS ≥10
+9 more

Side effects data

From 2012 Phase 3 trial • 256 Patients • NCT01005680
51%
Neutropenia
47%
Leukopenia
46%
Nausea
43%
Vomiting
35%
Anaemia
31%
Decreased appetite
26%
Haemoglobin decreased
26%
Fatigue
25%
Constipation
25%
White blood cell count decreased
24%
Neutrophil count decreased
19%
Alanine aminotransferase increased
13%
Platelet count decreased
12%
Rash
10%
Aspartate aminotransferase increased
10%
Thrombocytopenia
9%
Blood sodium decreased
8%
Hypokalaemia
7%
Insomnia
7%
Pyrexia
6%
Hyponatraemia
6%
Blood creatinine increased
6%
Lymphopenia
6%
Diarrhoea
6%
Dyspepsia
6%
Red blood cell count decreased
6%
Cough
4%
Dizziness
2%
Bone marrow failure
1%
Cerebral infarction
1%
Dyspnoea
1%
Ischaemic stroke
1%
Pulmonary embolism
1%
Embolism venous
1%
Superior vena cava syndrome
100%
80%
60%
40%
20%
0%
Study treatment Arm
Gemcitabine Plus Cisplatin (GC)
Pemetrexed Plus Cisplatin (PC)

Trial Design

2Treatment groups
Experimental Treatment
Active Control
Group I: Pembrolizumab + Lenvatinib + ChemotherapyExperimental Treatment8 Interventions
Participants receive pembrolizumab intravenously (IV) plus lenvatinib orally in combination with FP or TP in Part 1, or in combination with investigator's choice of chemotherapy with FP IV or TP IV or oxaliplatin, 5-FU and leucovorin (mFOLFOX6) IV in Part 2. Induction consists of pembrolizumab 400 mg once every 6-weeks (Q6W) for up to ~12 weeks plus lenvatinib 8 mg once daily (QD) for up to ~12 weeks plus chemotherapy with FP (cisplatin 80 mg/m^2 and 5-FU 4000 mg/m^2) or TP (paclitaxel 175 mg/m^2 and cisplatin 75 mg/m^2) once every 3 weeks (Q3W) for up to ~12 weeks or mFOLFOX6 (oxaliplatin 85 mg/m^2, 5-FU 400 mg/m^2 followed by 2400 mg/m^2, and leucovorin 400 mg/m^2 [or levoleucovorin 200 mg/m^2] once every 2 weeks [Q2W] for up to ~12 weeks). This is followed by consolidation with pembrolizumab 400 mg Q6W for up to 16 cycles (each cycle = 6 weeks; total pembrolizumab treatment duration is ~2 years) plus lenvatinib 20 mg QD until progressive disease or discontinuation.
Group II: Pembrolizumab + ChemotherapyActive Control7 Interventions
Participants receive pembrolizumab 400 mg IV Q6W for up to 18 cycles (each cycle = 6 weeks; total pembrolizumab treatment duration is ~2 years) in combination with investigator's choice of chemotherapy with FP (cisplatin 80 mg/m^2 IV Q3W for up to 6 administrations [up to ~18 weeks] and 5-FU 4000 mg/m^2 IV Q3W for up to 35 administrations [up to ~2 years]) or TP (paclitaxel 175 mg/m^2 and cisplatin 75 mg/m^2 Q3W for up 6 administrations [up to ~18 weeks]) or in combination with mFOLFOX6 (oxaliplatin 85 mg/m^2, 5-FU 400 mg/m^2 followed by 2400 mg/m^2 and leucovorin 400 mg/m^2 [or levoleucovorin 200 mg/m^2] IV Q2W for up to 52 administrations [approximately 2 years]), during Part 2.
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
5-FU
2014
Completed Phase 3
~3420
Lenvatinib
2020
Completed Phase 4
~2650
Cisplatin
2013
Completed Phase 3
~1940
Oxaliplatin
2011
Completed Phase 4
~2560
Levoleucovorin
2019
Completed Phase 2
~20
Leucovorin
2005
Completed Phase 4
~5730
Paclitaxel
2011
Completed Phase 4
~5380
Pembrolizumab
2017
Completed Phase 2
~2010

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 PD-1 inhibitors like pembrolizumab, tyrosine kinase inhibitors like lenvatinib, and cytotoxic chemotherapy. PD-1 inhibitors work by blocking the programmed death-1 (PD-1) pathway, which cancer cells use to evade the immune system, thereby allowing the immune system to recognize and attack the cancer cells. Tyrosine kinase inhibitors target specific enzymes (tyrosine kinases) involved in the signaling pathways that promote cancer cell growth and survival, effectively inhibiting tumor growth. Cytotoxic chemotherapy uses drugs that kill rapidly dividing cells, including cancer cells, by damaging their DNA or interfering with cell division. These treatments are crucial for esophageal cancer patients as they offer a multi-faceted approach to controlling and potentially reducing tumor burden, improving overall survival and progression-free survival.
Esophageal and Esophagogastric Junction Cancers, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology.

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Who is running the clinical trial?

Merck Sharp & Dohme Corp.Lead Sponsor
2,286 Previous Clinical Trials
4,581,150 Total Patients Enrolled
Merck Sharp & Dohme LLCLead Sponsor
3,919 Previous Clinical Trials
5,067,401 Total Patients Enrolled
Eisai Inc.Industry Sponsor
517 Previous Clinical Trials
158,070 Total Patients Enrolled

Media Library

5-FU (Fluoropyrimidine-based Chemotherapy) Clinical Trial Eligibility Overview. Trial Name: NCT04949256 — Phase 3
Esophageal Cancer Research Study Groups: Pembrolizumab + Lenvatinib + Chemotherapy, Pembrolizumab + Chemotherapy
Esophageal Cancer Clinical Trial 2023: 5-FU Highlights & Side Effects. Trial Name: NCT04949256 — Phase 3
5-FU (Fluoropyrimidine-based Chemotherapy) 2023 Treatment Timeline for Medical Study. Trial Name: NCT04949256 — Phase 3
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