Pembrolizumab + Lenvatinib + Chemo for Esophageal Cancer
Recruiting in Palo Alto (17 mi)
+216 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Waitlist Available
Sponsor: Merck Sharp & Dohme Corp.
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This trial tests a new combination of drugs and chemotherapy for advanced esophageal cancer. It targets patients whose cancer has spread and who need effective first-line treatment. The treatment works by enhancing the immune system, blocking cancer growth, and killing cancer cells.
Do I have to stop taking my current medications for the trial?
The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that you must have adequately controlled blood pressure with or without antihypertensive medications, and there are restrictions on certain treatments like immunosuppressive therapy and live vaccines. It's best to discuss your specific medications with the trial team.
What data supports the idea that Pembrolizumab + Lenvatinib + Chemo for Esophageal Cancer is an effective treatment?
The available research does not provide specific data on the effectiveness of Pembrolizumab + Lenvatinib + Chemo for Esophageal Cancer. However, it does mention that traditional treatments like cisplatin and 5-fluorouracil have a response rate of 25% to 35% in metastatic cases. Newer treatments, such as paclitaxel combined with cisplatin, show promise with less toxicity. Pembrolizumab has been compared to paclitaxel for gastro-esophageal junction cancer, suggesting it is a viable option, but specific data for the combination with Lenvatinib and chemotherapy in esophageal cancer is not provided.
12345What safety data is available for the treatment of esophageal cancer with Pembrolizumab, Lenvatinib, and chemotherapy?
The provided research includes safety data on various chemotherapy regimens involving drugs like fluorouracil (5-FU), cisplatin, and paclitaxel, which are part of the treatment for esophageal cancer. These studies highlight the significant gastrointestinal toxicity associated with traditional cisplatin/5-FU regimens and explore alternative combinations to improve the therapeutic index. The studies also evaluate the toxicity and efficacy of paclitaxel combined with cisplatin and 5-FU, noting the potential for improved outcomes with different combinations. However, specific safety data for the combination of Pembrolizumab, Lenvatinib, and chemotherapy is not directly addressed in these studies.
13678Is the drug combination of Pembrolizumab, Lenvatinib, and chemotherapy promising for esophageal cancer?
Yes, the combination of Pembrolizumab, Lenvatinib, and chemotherapy is promising for esophageal cancer. Pembrolizumab has shown superior effectiveness in improving survival rates when combined with chemotherapy for esophageal cancer. Lenvatinib, when used with Pembrolizumab, has been more effective than when used alone. This combination is approved for treating advanced esophageal cancer, indicating its potential benefits.
29101112Eligibility Criteria
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.Inclusion Criteria
My organs are functioning well.
My blood pressure is 150/90 or lower, and my medication hasn't changed in the last week.
I am not pregnant, breastfeeding, and if able to have children, I use effective birth control or practice abstinence.
+2 more
Exclusion Criteria
I have received treatment for advanced esophageal cancer that cannot be surgically removed.
I have cancer that has spread to my brain or spinal cord.
I have had serious heart problems in the last year.
+20 more
Participant Groups
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.
3Treatment groups
Experimental Treatment
Active Control
Group I: Part 2: Pembrolizumab + Lenvatinib + ChemotherapyExperimental Treatment8 Interventions
In the induction phase, participants receive pembrolizumab 400mg intravenously (IV) every 6 weeks (Q6W) for 2 cycles (each cycle length = 6 weeks) plus Lenvatinib 8 mg orally (PO) once daily (QD) 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) IV every 3 weeks for 4 administrations 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 6 administrations at the investigator's discretion (approximately 12 weeks). In the consolidation phase, participants receive pembrolizumab 400 mg IV Q6W for 16 cycles (each cycle length = 6 weeks) and Lenvatinib 20 mg PO until progressive disease or discontinuation (approximately 96 weeks).
Group II: Part 1: Pembrolizumab + Lenvatinib + ChemotherapyExperimental Treatment5 Interventions
In the induction phase, participants receive pembrolizumab 400mg intravenously (IV) every 6 weeks (Q6W) for 2 cycles (each cycle length = 6 weeks) plus Lenvatinib 8 mg orally (PO) once daily (QD) plus chemotherapy with FP (cisplatin 80 mg/m\^2 and 5-FU 400 mg/m\^2 followed by 2400 mg/m\^2) or TP (paclitaxel 175 mg/m\^2 and cisplatin 75 mg/m\^2) IV every 3 weeks for 4 administrations at the investigator's discretion (approximately 12 weeks). In the consolidation phase, participants receive pembrolizumab 400 mg IV Q6W for 16 cycles (each cycle length = 6 weeks) and Lenvatinib 20 mg PO until progressive disease or discontinuation (approximately 96 weeks).
Group III: Part 2: Pembrolizumab + ChemotherapyActive Control6 Interventions
Participants receive pembrolizumab 400 mg IV every 6 weeks for 18 cycles (each cycle length = 6 weeks, approximately 2 years) plus 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 \[approximately 2 years\]).
5-FU is already approved in United States, European Union, Canada, Japan for the following indications:
🇺🇸 Approved in United States as Fluorouracil for:
- Colorectal cancer
- Breast cancer
- Stomach cancer
- Pancreatic cancer
🇪🇺 Approved in European Union as Fluorouracil for:
- Colorectal cancer
- Breast cancer
- Stomach cancer
- Pancreatic cancer
- Skin cancer
🇨🇦 Approved in Canada as Fluorouracil for:
- Colorectal cancer
- Breast cancer
- Stomach cancer
- Pancreatic cancer
🇯🇵 Approved in Japan as Fluorouracil for:
- Colorectal cancer
- Breast cancer
- Stomach cancer
- Pancreatic cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Medical University of South Carolina-Hollings Cancer Center ( Site 0177)Charleston, SC
St. Luke's University Health Network ( Site 0185)Bethlehem, PA
Hotel-Dieu de Levis ( Site 0013)Levis, Canada
CancerCare Manitoba ( Site 0001)Winnipeg, Canada
More Trial Locations
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Who Is Running the Clinical Trial?
Merck Sharp & Dohme Corp.Lead Sponsor
Merck Sharp & Dohme LLCLead Sponsor
Eisai Inc.Industry Sponsor
References
Combined modality therapy in esophageal cancer: the Memorial experience. [2018]Over the past 20 years in the United States, esophageal cancer has shown the most rapid rate of increase of any solid tumor malignancy. Esophageal cancer is an aggressive disease, and poor survival is achieved with surgery or chemoradiation therapy alone. Ongoing trials are investigating the use of preoperative chemoradiation followed by surgical resection. Chemoradiation employing a combination of cisplatin and a continuous infusion of 5-fluorouracil (5-FU) is the most commonly used therapy. The significant gastrointestinal toxicity of traditional cisplatin/5-FU-based regimens has prompted the evaluation of new agents in combined-modality therapy. The Memorial Sloan-Kettering Cancer Center has conducted chemoradiation trials with weekly paclitaxel/cisplatin and irinotecan/cisplatin, and the results suggest that this regimen has the potential to improve the therapeutic index without compromising efficacy. Randomized trials are now being conducted to evaluate the tolerance and efficacy of paclitaxel/cisplatin in comparison with paclitaxel/5-FU combined with radiotherapy in locally advanced esophageal cancer. The incorporation of these non-5-FU-based therapies with novel biologic agents is planned.
Chemotherapy in esophageal cancer. [2022]The incidence of esophageal cancer continues to increase due to a rapid increase in adenocarcinoma of the distal esophagus and gastroesophageal junction. At least 50% of patients present with metastatic cancer and most patients with localized disease will develop metastases despite potentially curative local therapy. Thus, the majority of esophageal cancer patients will become candidates for palliative chemotherapy. Traditionally, single agents effective in this disease have included cisplatin, 5-fluorouracil, and mitomycin. The combination of cisplatin and continuous-infusion 5-fluorouracil is the standard for both squamous cell carcinoma and adenocarcinoma, with a 25% to 35% response rate in metastatic disease. More recently, paclitaxel has shown favorable results as a single agent or in combination with cisplatin in both disease histologies. One-hour weekly paclitaxel, a promising schedule with little toxicity, is under active investigation. Weekly irinotecan and cisplatin is a highly effective new regimen in both adenocarcinoma and squamous cell carcinoma with relatively little toxicity. Vinorelbine has demonstrated response in squamous cell carcinoma and has less toxicity than its predecessor, vindesine. Use of newer agents in combination with concurrent radiotherapy in locally advanced disease is the subject of ongoing clinical trials.
A Pilot Trial of S-1 and Paclitaxel in Unresectable or Postoperative Recurrent Esophageal Squamous Cell Carcinoma Pretreated by Fluorouracil, Cisplatin, and Docetaxel Chemotherapy. [2019]This study documents the clinical efficacy and toxicity of S-1 and paclitaxel (S1/PTX) in patients with unresectable or postoperative recurrent esophageal squamous cell carcinoma (ESCC) who had been previously treated with fluorouracil (5FU), cisplatin, and docetaxel.
A new combination chemotherapy with cis-diammine-glycolatoplatinum (Nedaplatin) and 5-fluorouracil for advanced esophageal cancers. [2019]The efficacy of a new chemotherapeutic combination consisting of Cis-diammineglycolatoplatinum (Nedaplatin), a derivative of cisplatin (CDDP), and 5-fluorouracil (5FU) was evaluated in patients with advanced esophageal carcinomas.
Pembrolizumab versus paclitaxel for previously treated, advanced gastro-esophageal junction cancer: A systematic review and meta-analysis of randomized clinical trials. [2022]This paper aims to compare the effectiveness and safety of pembrolizumab and paclitaxel as a second line for patients with locally advanced gastroesophageal cancer.
Pilot study of preoperative combined modality treatment for locally advanced operable oesophageal carcinoma: toxicities and long-term outcome. [2019]Paclitaxel, a radiosensitiser, has significant activity in oesophageal cancer. We aimed to conduct a feasibility study of preoperative chemoradiation using paclitaxel, cisplatin and 5-fluorouracil (5-FU).
A phase II study on continuous infusional paclitaxel and 5-Fu as first-line chemotherapy for patients with advanced esophageal cancer. [2022]This study was performed to evaluated the efficacy and safety of continuous infusional paclitaxel and 5-Fu as first-line chemotherapy in patients with advanced esophageal squamous cell cancer (ESCC).
Phase II trial of paclitaxel, fluorouracil, and cisplatin in patients with advanced carcinoma of the esophagus. [2022]We have previously identified paclitaxel as an active single agent in the treatment of esophageal cancer. We performed a phase II trial of paclitaxel in combination with cisplatin and fluorouracil (5-FU), conventionally used chemotherapy for esophageal cancer. The antitumor response, toxicity, and survival of patients treated with the three-drug regimen were evaluated.
Immuno-oncology for esophageal cancer. [2021]Esophageal cancer (EC) is the seventh most common cancer, with a poor prognosis for metastatic EC patients and limited effective drugs for treatment. Nivolumab and pembrolizumab, monoclonal antibodies that inhibit interactions of PD-1 and its ligand (PD-L1), which induce lymphocyte activation, have antitumor activity. The ATTRACTION-3 trial compared nivolumab with taxane after first-line chemotherapy and demonstrated superior overall survival (OS) for esophageal squamous cell carcinoma. The KEYNOTE-181 trial that compared pembrolizumab with chemotherapy demonstrated superior OS for EC with a PD-L1 combined positive score ≥10. Trials to evaluate efficacy of combined cytotoxic agents and immune checkpoint inhibitors (ICI) as first-line chemotherapies, ICI-containing chemoradiotherapy, and pre/postoperative chemotherapy are ongoing and might provide important data to improve clinical outcomes.
Cost Effectiveness of Adding Pembrolizumab to Platinum and Fluoropyrimidine-Based Chemotherapy as First-Line Treatment for Advanced Esophageal Cancer: A US Healthcare Payer's Perspective. [2022]Pembrolizumab plus cisplatin and fluorouracil demonstrated superior efficacy and comparable safety compared with fluorouracil and cisplatin (FP) as first-line treatment for locally advanced unresectable or metastatic carcinoma of the esophagus and gastroesophageal junction adenocarcinoma in a phase III trial (KEYNOTE-590). This study evaluated the cost effectiveness of pembrolizumab plus FP versus FP and versus a blended chemotherapy comparator including FP, carboplatin plus paclitaxel, FOLFOX, FOLFIRI, docetaxel plus FP, trastuzumab plus FP, and trastuzumab plus FOLFOX from a US healthcare payer's perspective.
Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. [2023]Pembrolizumab (Keytruda) has been approved to treat metastatic or locally advanced esophageal or gastroesophageal junction cancer. It is used in combination with platinum- and fluoropyrimidine-based chemotherapy.
Esophagitis as a complication of the combination of lenvatinib and pembrolizumab for advanced endometrial cancer: A case report. [2023]Pembrolizumab is a monoclonal antibody targeting the programmed cell death protein 1 (PD-1). It is used in the management and treatment of various oncologic conditions. To name a few: refractory and advanced melanoma, non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), renal cell carcinoma and gastric cancer. It is also approved for metastatic mismatch repair deficient (dMMR) endometrial carcinoma after failure of front-line chemotherapy. Lenvatinib is an oral multikinase inhibitor that targets vascular endothelial growth factor receptors 1-3, fibroblast growth factor receptors 1-4, platelet-derived growth factor receptor-a, RET, and KIT. The combination of lenvatinib and pembrolizumab has proven to be more effective together than as monotherapy. Here, we present the case of a patient who probably developed lenvatinib-related esophagitis, a complication not previously described in the literature to our knowledge.Case presentation.We describe a 65 years old female with metastatic endometrial cancer who presented dysphagia after a few months of lenvatinib plus pembrolizumab treatment. Upper endoscopy results revealed a very fragile upper esophageal mucosa with mucosal lacerations, consistent with grade 2 esophagitis. The biopsy showed esophagitis with mixed lymphocytic and eosinophilic inflammation and apoptotic component. Pembrolizumab was then stopped pending the results of the biopsy, following the recommendations of the gastroenterologist. Dysphagia, however, remained unchanged. In the meantime, the lenvatinib had to be stopped due to a dental procedure, and the patient noted a marked improvement in her symptoms. After discussion with the gastroenterologist, pembrolizumab was resumed and lenvatinib was suspended. The patient was also started on a PPI twice daily since the first digestive exploration. 1 month later, upper endoscopy showed complete recovery, the patient's symptoms improved, and lenvatinib was resumed. However, symptoms of dysphagia resumed a few days later. Lenvatinib was finally resumed at a reduced dose without reappearance in her symptoms.