Chemoradiation and Pembrolizumab Followed by Pembrolizumab and Lenvatinib Before Surgery for the Treatment of Non-metastatic Esophageal or Esophageal/Gastroesophageal Junction Cancer

NCT04929392 | Active Not Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: 20742NCI-2021-03223P30CA033572
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies the effect of chemoradiation and pembrolizumab followed by pembrolizumab and lenvatinib before surgery in treating patients with esophageal or esophageal/gastroesophageal junction cancer that has not spread to other places in the body (non-metastatic). Pembrolizumab is an immunotherapy drug that works by harnessing the immune system to attack cancer. Lenvatinib is an anti-cancer drug that works by stopping or slowing down the growth of cancer cells. Chemotherapy drugs, such as carboplatin and paclitaxel, 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 x-rays to kill tumor cells and shrink tumors. Giving chemoradiation and pembrolizumab followed by pembrolizumab and lenvatinib before surgery may kill more tumor cells.

Conditions

Clinical Stage I Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage II Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage IIA Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage IIB Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8; Esophageal Adenocarcinoma; Esophageal Squamous Cell Carcinoma; Pathologic Stage I Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IA Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IB Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IC Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage II Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IIA Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IIB Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IIIA Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IIIB Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8

Outcome Measures

Primary Outcomes (2)

• Pathological complete response (CR)

  Defined as no residual cancer cells, including lymph nodes under pathologic examination of the surgically resected specimen and/or a Tumor Regression Score of 0 by the College of American Pathologist (CAP) Cancer Protocol for Esophageal Carcinoma. Pathological CR rate will be estimated by the proportion of patients achieving pathological CR, along with the 95% exact binomial confidence interval.

  At 14 weeks after starting protocol chemoradiotherapy

• Clinical complete response (CR)

  Defined as no radiographic evidence of disease on positron emission tomography /computed tomography or CT imaging. Clinical CR rate will be estimated by the proportion of patients achieving clinical CR, along with the 95% exact binomial confidence interval.

  At 14 weeks after starting protocol chemoradiotherapy

Secondary Outcomes (4)

• Immune-mediated tumor cytotoxicity

  Up to 3 years

• Incidence of adverse events

  Up to 90 days post-treatment

• Disease-free survival (DFS)

  Up to 3 years

• Overall survival (OS)

  Up to 3 years

Study Arms (1)

Treatment (chemoradiation, pembrolizumab, lenvatinib)

EXPERIMENTAL

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.

Drug: Carboplatin; Procedure: Endoscopic Biopsy; Radiation: External Beam Radiation Therapy; Drug: Lenvatinib Mesylate; Drug: Paclitaxel; Biological: Pembrolizumab; Procedure: Resection

Interventions

Carboplatin DRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Treatment (chemoradiation, pembrolizumab, lenvatinib)

Endoscopic Biopsy PROCEDURE

Undergo endoscopic biopsy

Also known as: Endoscopy and Biopsy

Treatment (chemoradiation, pembrolizumab, lenvatinib)

External Beam Radiation Therapy RADIATION

Undergo EBRT

Also known as: Definitive Radiation Therapy, EBRT, External Beam Radiation, External Beam Radiotherapy, External Beam RT, external radiation, External Radiation Therapy, external-beam radiation, Radiation, External Beam

Treatment (chemoradiation, pembrolizumab, lenvatinib)

Lenvatinib Mesylate DRUG

Given PO

Also known as: 4-[3-Chloro-4-(N''-cyclopropylureido)phenoxy]7-methoxyquinoline-6-carboxamide Mesylate, E7080, Lenvima, Multi-Kinase Inhibitor E7080

Treatment (chemoradiation, pembrolizumab, lenvatinib)

Paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Treatment (chemoradiation, pembrolizumab, lenvatinib)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (chemoradiation, pembrolizumab, lenvatinib)

Resection PROCEDURE

Undergo surgical resection

Also known as: Surgical Resection

Treatment (chemoradiation, pembrolizumab, lenvatinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented informed consent of the participant and/or legally authorized representative
• Agreement to allow the use of archival tissue from diagnostic tumor biopsies
• If unavailable, exceptions may be granted only with study principal investigator (PI) approval
• Age \>= 18 years
• Eastern Cooperative Oncology Group (ECOG) =\< 1
• Non-metastatic cancer of the esophagus OR esophagus and gastroesophageal junction (GEJ; tumor extending =\< 2 cm into the stomach)
• Confirmed stage I (T1N1 only)-IVA diagnosis of one of the following:
• Squamous cell; OR
• Adenocarcinoma; OR
• Mixed adenosquamous carcinoma
• Deemed appropriate for neoadjuvant chemoradiation by the multidisciplinary team (surgeon, medical oncologist, and radiation oncologist)
• Chemotherapy defined as weekly carboplatin/paclitaxel; AND
• Radiation defined as external beam radiotherapy defined as: 50.4 Gy as per institutional and national treatment guidelines
• Deemed appropriate for esophagectomy or repeat endoscopic biopsies if non-operative management is pursued
• Absolute neutrophil count (ANC) \>= 1500/mm\^3 (performed within 14 days prior to day 1 of study participation/ 1st endoscopic biopsy unless otherwise stated)

You may not qualify if:

• Immune checkpoint inhibitor(s) (e.g. anti-PD-1, anti-CTLA4)
• Multi-tyrosine kinase inhibitor(s) (e.g. lenvatinib)
• Radiotherapy within 21 days prior to day 1 of study participation
• Investigational agent within 21 days prior to day 1 of study participation
• Live-virus vaccination within 30 days prior to day 1 of study participation
• Systemic cytotoxic chemotherapy, antineoplastic biologic therapy, or major surgery within 21 days of study participation
• Chronic systemic steroid therapy or on any other form of immunosuppressive medication
• Coumarin-based anticoagulants
• Unstable or untreated brain/leptomeningeal metastasis
• Clinically active diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, or abdominal carcinomatosis (known risks factors for bowel perforation)
• Severe hypersensitivity reaction to treatment with another antibody and/or hypersensitivity to lenvatinib and/or any of its excipients
• Active autoimmune disease that has required systemic treatment in the past 2 years
• Known history of human immunodeficiency virus (HIV), hepatitis B or hepatitis C (with confirmation of negative hepatitis B surface antigen \[HBSAg\], hepatitis B virus \[HBV\] polymerase chain reaction \[PCR\], and hepatitis C virus \[HCV\] PCR)
• History of pneumonitis (non-infectious) that required steroids or current pneumonitis
• Known history of active tuberculosis

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Adenocarcinoma Of Esophagus; Esophageal Squamous Cell Carcinoma

Interventions

Carboplatin; Endoscopic Mucosal Resection; Endoscopy; Biopsy; Radiation; lenvatinib; Paclitaxel; Taxes; pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Endoscopy, Gastrointestinal; Endoscopy, Digestive System; Diagnostic Techniques, Digestive System; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Digestive System Surgical Procedures; Surgical Procedures, Operative; Minimally Invasive Surgical Procedures; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Specimen Handling; Investigative Techniques; Physical Phenomena; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations

Study Officials

• Vincent Chung, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2021
• First Posted: June 18, 2021
• Study Start: January 25, 2022
• Primary Completion (Estimated): April 25, 2027
• Study Completion (Estimated): April 25, 2027
• Last Updated: September 4, 2025

Record last verified: 2025-08

Locations

US (1)