Overview

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

Status:
Recruiting
Trial end date:
2023-12-31
Target enrollment:
0
Participant gender:
All
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.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
City of Hope Medical Center
Collaborator:
National Cancer Institute (NCI)
Treatments:
Albumin-Bound Paclitaxel
Carboplatin
Lenvatinib
Paclitaxel
Pembrolizumab
Criteria
Inclusion Criteria:

- 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)

- Platelets >= 100,000/mm^3 (performed within 14 days prior to day 1 of study
participation/ 1st endoscopic biopsy unless otherwise stated)

- Serum total bilirubin =< 1.5 x upper limit of normal (ULN) OR direct bilirubin =< ULN
if total bilirubin levels > 1.5 x ULN (performed within 14 days prior to day 1 of
study participation/1st endoscopic biopsy unless otherwise stated)

- Aspartate aminotransferase (AST) =< 2 x ULN (performed within 14 days prior to day 1
of study participation/1st endoscopic biopsy unless otherwise stated)

- Alanine aminotransferase (ALT) =< 2 x ULN (performed within 14 days prior to day 1 of
study participation/1st endoscopic biopsy unless otherwise stated)

- Creatinine =< 1.5 x ULN OR for patients with creatinine > 1.5 x ULN creatinine
clearance of >= 60 mL/min per 24 hour urine test or the Cockcroft-Gault formula
(performed within 14 days prior to day 1 of study participation/1st endoscopic biopsy
unless otherwise stated)

- International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN (performed
within 14 days prior to day 1 of study participation/1st endoscopic biopsy unless
otherwise stated)

- Activated partial thromboplastin time (aPTT) =< 1.5 x ULN (performed within 14 days
prior to day 1 of study participation/1st endoscopic biopsy unless otherwise stated)

- Female of childbearing potential only: Negative urine or serum pregnancy test. If the
urine test is positive or cannot be confirmed as negative, a serum pregnancy test will
be required (performed within 14 days prior to day 1 of study participation/1st
endoscopic biopsy unless otherwise stated)

- Agreement by women of childbearing potential (WOCBP) and males of childbearing
potential to use an effective method of birth control or abstain from heterosexual
activity for the course of the study through at least 120 days after the last dose of
protocol therapy

- Childbearing potential defined as not being surgically sterilized (men and women)
or have not been free from menses for > 1 year (women only)

Exclusion Criteria:

- 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

- Diagnosed with or treated for cancer within the previous two years, other than
histologies listed in inclusion criteria or non-melanoma carcinoma of the skin

- Female only: Pregnant or breastfeeding

- Any other condition that would, in the investigator's judgment, contraindicate the
patient's participation in the clinical study due to safety concerns with clinical
study procedures

- Prospective participants who, in the opinion of the investigator, may not be able to
comply with all study procedures (including compliance issues related to
feasibility/logistics)