Inclusion Criteria:

• Age ≥ 18 years.
• Histological confirmation of esophageal or gastroesophageal junction adenocarcinoma, AJCC 8th ed stage T1-4N0-3M0.
• Candidate for trimodality therapy: neoadjuvant chemotherapy and esophagectomy.
• Surgical consultation to confirm that patient is an appropriate candidate for esophagectomy.
• Medical oncology consultation to confirm that patient is an appropriate candidate for chemotherapy.
• ECOG Performance Status (PS) ≤ 1 (Appendix I).
• Negative pregnancy test done ≤ 7 days prior to registration, for women of childbearing potential only.
• Ability to provide written informed consent and complete questionnaire(s) by themselves or with assistance.
• Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study) and provide blood samples for correlative research purposes (see Sections 6, 14).

Exclusion Criteria:

• Clinical or biopsy-proven distant metastatic disease (AJCC 8th ed stage TanyNanyM1).
• Cervical or upper esophageal tumor.
• Prior chemotherapy or radiotherapy for esophageal cancer OR history of radiotherapy to the thorax.
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgement of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with proper assessment of adverse events.
• Receiving any investigational agent which would be considered as a treatment for the primary neoplasm OR other active malignancy ≤ 1 year prior to registration that is considered by the investigator to interfere with the current treatment or measurement of outcomes.
• Any of the following:
  • Pregnant women;
  • Nursing women;
  • Men or women of childbearing potential who are unwilling to employ adequate contraception.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 2/14/23. Questions regarding updates should be directed to the study team contact.