The following clinical trials represent a selection of key studies currently recruiting patients with esophageal cancer for inclusion in investigations of new therapies and new regimens of existing treatments for the disease. Each clinical trial description includes the NLM Identifier to be used as a reference with ClinicalTrials.gov. This information can help oncology practice managers and providers direct eligible patients to one of these clinical trials.
1 Durvalumab plus Definitive Chemoradiation versus Definitive Chemoradiation Alone in ESCC
The purpose of this randomized, double-blind, placebo-controlled, multicenter, international, phase 3 study is to assess the efficacy and safety of durvalumab (Imfinzi) administered concurrently with definitive chemoradiation versus definitive chemoradiation alone in patients with locally advanced, unresectable esophageal squamous-cell carcinoma (ESCC). Patients aged ≥18 years with histologically or cytologically confirmed locally advanced ESCC whose disease is unresectable and have been deemed suitable for definitive chemoradiation therapy, who have a European Cooperative Oncology Group (ECOG) performance status of 0 or 1, have adequate organ and bone marrow function, and who have a life expectancy of >3 months may be eligible if other criteria are met. Eligible patients will be randomized in a 2:1 ratio to receive either durvalumab plus definitive chemoradiation or placebo plus definitive chemoradiation.
The primary outcome measure is progression-free survival (PFS) as per RECIST version 1.1 as assessed by blinded independent central review. The secondary outcome measure is overall survival (OS) in all randomized patients and in patients with PD-L1–high tumors until the date of death. Other outcome measures include the assessment of the safety and tolerability profile of both trial arms. The study plans to enroll 600 participants throughout the United States and worldwide. For more information, contact the AstraZeneca Clinical Study Information Center at 1-877-240-9479 or
2 Proton Beam Therapy versus Intensity Modulated Photon Radiotherapy in Esophageal Cancer
The purpose of this randomized, parallel, phase 3 trial is to evaluate the efficacy of proton beam radiation therapy versus intensity modulated photon radiotherapy in the treatment of patients with stage I-IVa esophageal cancer. Patients aged ≥18 years with histologically proven diagnosis of adenocarcinoma or squamous-cell carcinoma of the thoracic esophagus or gastroesophageal junction; who have a Zubrod performance status of 0, 1, or 2; and who have had induction chemotherapy with FOLFOX (folinic acid [leucovorin], fluorouracil, and oxaliplatin [Eloxatin]) within 10 to 90 days of registration may be eligible if other criteria are met. Eligible patients will be randomized to receive either proton beam radiation therapy 5 days a week for 5.5 weeks, chemotherapy, and esophagectomy within 4 to 8 weeks of completing chemotherapy and radiation therapy; or intensity modulated photon radiotherapy 5 days a week for 5.5 weeks, chemotherapy, and esophagectomy within 4 to 8 weeks after completing chemotherapy and radiation therapy.
The primary outcome measures are OS, from the date of randomization to the date of death due to any cause or date of last follow-up for patients without a reported OS event, and the incidence of specific grade ≥3 cardiopulmonary adverse events (AEs) that are definitely, probably, or possibly related to protocol treatment. Secondary outcome measures include pathologic response rate at time of surgery, grade 4 lymphopenia during chemoradiation, lymphocyte counts up to 8 weeks after chemoradiation, locoregional failure, distant metastatic-free survival, PFS, quality-adjusted life-years as per EuroQol five-dimensional questionnaire, and cost–benefit economic analysis of treatment. The study plans to enroll 300 participants throughout the United States. For more information, contact the recruiting sites directly. The NLM identifier is NCT03801876.
3 Atezolizumab with or without Tiragolumab versus Placebo in Unresectable ESCC
The purpose of this randomized, double-blind, placebo-controlled, phase 3 study is to evaluate the efficacy and safety of tiragolumab (MTIG7192A) plus atezolizumab (Tecentriq) versus atezolizumab alone versus placebo in patients with unresectable ESCC whose cancers have not progressed following definitive concurrent chemoradiotherapy. Patients aged ≥18 years with a histologically or cytologically confirmed diagnosis of ESCC whose disease is unresectable and ineligible for curative surgery, who have an ECOG performance status of 0 or 1, who have received definitive concurrent chemoradiotherapy, and who have adequate hematologic and end-organ function before randomization may be eligible if other criteria are met. Eligible patients will be randomized in a 1:1:1 ratio to receive tiragolumab 600 mg intravenously (IV) every 3 weeks on day 1 of each 21-day cycle plus atezolizumab 1200 mg IV every 3 weeks on day 1 of each 21-day cycle (arm A); atezolizumab 1200 mg IV plus tiragolumab-matching placebo every 3 weeks on day 1 of each 21-day cycle (arm B); or tiragolumab-matching placebo and atezolizumab-matching placebo IV every 3 weeks on day 1 of each 21-day cycle (arm C).
The primary outcome measures include investigator-assessed PFS between arm A and arm C, OS between arm A and arm C, and OS between arm B and arm C. Secondary outcome measures include investigator-assessed PFS between arm B and arm C and between arm A and arm B; OS between arm A and arm B; independent review facility (IRF)-assessed PFS; investigator-assessed and IRF-assessed confirmed objective response rate (ORR); investigator-assessed and IRF-assessed duration of objective response (DOR); the percentage of participants with AEs; and the serum concentration of tiragolumab and atezolizumab. The study plans to enroll 750 participants throughout the United States and worldwide. For more information, contact Roche at 1-888-662-6728,
4 Pembrolizumab plus Lenvatinib plus Chemotherapy versus Standard of Care as First-Line Treatment in Metastatic ESCC
The purpose of this randomized, parallel, open-label, phase 3 study is to assess the efficacy and safety of pembrolizumab (Keytruda) plus lenvatinib (Lenvima) plus chemotherapy compared with the standard-of-care treatment of pembrolizumab plus chemotherapy as first-line treatment in patients with metastatic ESCC. Patients aged ≥18 years with a histologically or cytologically confirmed diagnosis of metastatic ESCC who have adequate organ function and have adequately controlled blood pressure with or without antihypertensive medications may be eligible if other criteria are met. In part 1 of the study, eligible patients will receive pembrolizumab 400 mg IV once every 6-week cycle for up to 2 cycles, plus lenvatinib 8 mg orally (PO) once daily for up to 12 weeks, plus cisplatin and 5-fluorouracil for up to 12 weeks. In part 2 of the study, eligible patients will be randomized to receive pembrolizumab 400 mg IV once every 6-week cycle for up to 2 cycles, plus lenvatinib 20 mg PO once daily for up to 12 weeks, plus investigator’s choice of chemotherapy for up to 12 weeks; or pembrolizumab 400 mg IV once every 6-week cycle for up to 18 cycles plus investigator’s choice of chemotherapy with cisplatin and 5-fluorouracil.
The primary outcome measures in part 1 of the study are the number of patients with dose-limiting toxicities and AEs, and the number of patients who discontinued study treatment due to an AE. Primary outcome measures in part 2 of the study are OS and PFS per RECIST version 1.1 as assessed by blinded independent central review. Secondary outcome measures in part 2 are ORR and DOR in all patients; OS, PFS, ORR, and DOR in patients with PD-L1 combined positive score ≥10; the number of patients with AEs; and the number of patients who discontinued study treatment due to an AE. The study plans to enroll 862 participants throughout the United States and worldwide. For more information, contact Merck Sharp & Dohme Corp. at 1-888-577-8839 or
5 Radiotherapy plus Chemotherapy versus Chemotherapy Alone in Oligometastatic HER2-Negative Esophageal and Gastric Adenocarcinoma
The purpose of this randomized, sequential assignment, phase 3 study is to evaluate the efficacy of adding radiotherapy to the usual treatment of chemotherapy versus chemotherapy alone in the treatment of patients with oligometastatic HER2-negative esophageal and gastric adenocarcinoma. Patients aged ≥18 years with histologically confirmed oligometastatic HER2-negative disease, who have an ECOG performance status of 0-1, who are hematologically stable, and who have had previous definitive treatment for early-stage disease with either surgery or chemoradiation in which recurrent disease developed >6 months after completion of all previous therapies may be eligible if other criteria are met. Eligible patients will be randomized to 1 of 2 arms in the induction phase of the trial: oxaliplatin (Eloxatin), leucovorin, and 5-fluorouracil IV on days 1 and 15 every 28 days for up to 4 cycles (arm A), or oxaliplatin IV on day 1 and capecitabine PO twice daily on days 1 to 14 every 21 days for up to 6 cycles (arm B). Participants in arm A of the study in part 2 will be randomized to undergo radiation therapy for up to 15 days 1 week after induction, then receive the same chemotherapy for 2 years within 2 to 4 weeks after radiation therapy (arm C), or the continuation of the same chemotherapy for 2 years (arm D). Participants in arm B of the study in part 2 will be randomized to receive the same treatment schedule with their respective chemotherapy regimens (arm E and arm F).
The primary outcome measure is OS from the time of randomization up to 5 years after treatment. Secondary outcome measures include the incidence of AEs in all participants and PFS from the time of randomization up to 5 years after treatment. The study plans to enroll 314 participants throughout the United States. For more information, contact Nataliya V. Uboha, MD, PhD, at 1-608-265-9966 or
6 Tucatinib, Trastuzumab, Ramucirumab, and Paclitaxel versus Ramucirumab and Paclitaxel in Previously Treated HER2-Positive Gastroesophageal Cancer
The purpose of this randomized, double-blind, placebo-controlled, phase 2/3 study is to evaluate whether the addition of tucatinib (Tukysa) and trastuzumab (Herceptin) to a ramucirumab (Cyramza) and paclitaxel combination is superior to a ramucirumab and paclitaxel combination in the treatment of patients with previously treated, locally advanced, unresectable or metastatic HER2-positive gastroesophageal cancer. Patients aged ≥18 years with histologically or cytologically confirmed, locally advanced, unresectable, or metastatic HER2-positive disease, who have received previous treatment with an HER2-directed antibody, whose disease had progressed during or after first-line therapy, who have an ECOG performance status of 0 or 1, and who have a life expectancy of >3 months may be eligible if other criteria are met. In phase 2 of the trial, patients will receive tucatinib 300 mg PO twice daily; trastuzumab loading dose of 6 mg/kg IV on day 1 of cycle 1, followed by 4 mg/kg IV on day 15 of cycle 1 and then days 1 and 15 of each cycle thereafter; ramucirumab 8 mg/kg IV on days 1 and 15 of each cycle; and paclitaxel 60 or 80 mg/m2 IV on days 1, 8, and 15 of each cycle. In phase 3 of the trial, patients will be randomized to either the same therapy as in phase 2 (arm 3A); ramucirumab plus paclitaxel plus tucatinib and trastuzumab placebos (arm 3B); or tucatinib plus ramucirumab plus paclitaxel plus a trastuzumab placebo (arm 3C).
The primary outcome measures in phase 2 are the incidence of dose-limiting toxicities, AEs, laboratory abnormalities, and dose modifications. The primary outcome measures in phase 3 are OS from the time of randomization to death due to any cause and PFS per RECIST version 1.1. Secondary outcome measures include the area under the plasma concentration-time curve to the time of last quantifiable concentration, maximum observed concentration, and trough concentration of tucatinib and paclitaxel in phase 2; PFS, confirmed ORR, DOR, disease control rate, and the incidence of AEs, laboratory abnormalities, and dose modifications in phase 3; and confirmed ORR, DOR, and disease control rate for both phase 2 and phase 3. The study plans to enroll 578 participants throughout the United States and worldwide. For more information, contact Seagen Trial Information Support at 1-866-333-7436 or
7 Pembrolizumab versus Placebo in Patients Receiving Chemotherapy and Radiation Therapy for Esophageal Carcinoma
The purpose of this randomized, double-blind, placebo-controlled, phase 3 study is to assess the efficacy and safety of treatment with definitive chemoradiotherapy plus pembrolizumab (Keytruda) compared with treatment with definitive chemoradiotherapy plus placebo in patients with esophageal carcinoma. Patients aged ≥18 years with histologically or cytologically confirmed diagnosis of ESCC, gastroesophageal carcinoma, or esophageal adenocarcinoma, who have been deemed suitable for definitive chemoradiotherapy and ineligible for curative surgery, who have an ECOG performance status of 0 to 1, and who have adequate organ function may be eligible if other criteria are met. Eligible participants will be randomized to receive either pembrolizumab 200 mg IV on day 1 of each 3-week cycle for 8 cycles followed by pembrolizumab 400 mg on day 1 of each 6-week cycle for 5 cycles plus investigator’s choice of chemotherapy, or pembrolizumab placebo plus investigator’s choice of chemotherapy.
The primary outcome measures include OS and event-free survival, defined as the time from randomization to a local, regional, or distant recurrence as assessed by blinded independent central review based on imaging or biopsy or death from any cause. Secondary outcome measures include the number of participants with an AE and the number of participants discontinuing study treatment due to an AE. The study plans to enroll 600 participants throughout the United States and worldwide. For more information, contact Merck Sharp & Dohme Corp. at 1-888-577-8839 or
8 Perioperative Nivolumab and Ipilimumab in Locoregional Esophageal and Gastroesophageal Junction Adenocarcinoma
The purpose of this randomized, parallel, phase 2/3 study is to evaluate the usefulness of treatment with nivolumab (Opdivo) and ipilimumab (Yervoy) in addition to standard-of-care chemotherapy and radiation therapy in patients with esophageal and gastroesophageal junction adenocarcinoma who are undergoing surgery. Patients aged ≥18 years with histologically confirmed disease, who have an ECOG performance status of 0-1 before esophagectomy and 0-2 after esophagectomy, who have not received previous immunotherapy, who do not have a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of study treatment, and who are hematologically stable may be eligible if other criteria are met. Eligible participants will be randomized to receive either carboplatin and paclitaxel IV once weekly and radiation therapy once daily for 5 days beginning on day 1 of each 5-week cycle (arm A); arm A treatment plus nivolumab IV on days 1 and 15 of each 5-week cycle (arm B); nivolumab IV on day 1 every 2 weeks for up to 12 cycles (arm C); or arm C treatment plus ipilimumab IV on day 1 of cycles 1, 4, 7, and 10 for up to 12 cycles (arm D).
The primary outcome measures include pathologic complete response of arm A and arm B and disease-free survival of arm C versus arm D. Secondary outcome measures include the incidence of AEs and OS in all arms, and disease-free survival in arm C versus arm D. The study plans to enroll 278 participants throughout the United States. For more information, contact the recruiting sites directly. The NLM identifier is NCT03604991.
9 Sintilimab versus Placebo with Chemotherapy in Unresectable, Locally Advanced, Recurrent, or Metastatic ESCC
The purpose of this randomized, double-blind, multicenter, phase 3 study is to evaluate the efficacy and safety of sintilimab (Tyvyt) versus placebo in combination with chemotherapy for the first-line treatment of patients with unresectable, locally advanced, recurrent, or metastatic ESCC. Patients aged 18 to 75 years with histopathologically confirmed unresectable, locally advanced, recurrent, or metastatic ESCC who have an ECOG performance status of 0 or 1, who have at least 1 measurable lesion as per RECIST version 1.1, and who have been deemed unsuitable for definitive treatment, such as definitive chemoradiotherapy and/or surgery, may be eligible if other criteria are met. Eligible participants will be randomized to receive either sintilimab 3 mg/kg IV (weight <60 kg) or 200 mg IV (weight ≥60 kg) every 3 weeks on day 1 of each cycle plus investigator’s choice of chemotherapy, or placebo plus investigator’s choice of chemotherapy.
The primary outcome measures include OS in the overall population and OS in the PD-L1–positive population. Secondary outcome measures include ORR, PFS, disease control rate, and DOR in the overall population, and the ORR, disease control rate, DOR, and PFS in the PD-L1–positive population. The study plans to enroll 746 participants throughout the United States and worldwide. For more information, contact Winnie Leung at