Pembrolizumab and Chemoradiotherapy for the Treatment of Unresectable Gastroesophageal Cancer

Running, not enrolling · Phase 1

Conditions studied: Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8, Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8, Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8, Clinical Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8, Localized Gastroesophageal Junction Adenocarcinoma, Locally Advanced Gastroesophageal Junction Adenocarcinoma, Pathologic Stage III 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, Pathologic Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8, Postneoadjuvant Therapy Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8, Postneoadjuvant Therapy Stage IIIA Gastroesophageal Junction Adenocarcinoma AJCC v8, Postneoadjuvant Therapy Stage IIIB Gastroesophageal Junction Adenocarcinoma AJCC v8, Postneoadjuvant Therapy Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8, Postneoadjuvant Therapy Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8, Postneoadjuvant Therapy Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8, Unresectable Gastroesophageal Junction Adenocarcinoma

In brief

This phase I trial investigates how well pembrolizumab and chemoradiotherapy works in treating patients with gastroesophageal cancer that cannot be removed by surgery (unresectable). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as fluorouracil, oxaliplatin and docetaxel 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 photons to kill tumor cells and shrink tumors. Giving pembrolizumab together with chemoradiotherapy may help to control gastroesophageal cancer.

Key facts

Study ID: NCT04522336
Run by: M.D. Anderson Cancer Center
People needed: 16
Starts: 2020-09-16
Expected to finish: 2027-07-18
Last updated by the study team: 2026-03-05

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Participants with histologically confirmed diagnosis of unresectable gastroesophageal adenocarcinoma will be enrolled in this study for systemic treatment first
Have histologically documented locally advanced unresectable cancer or localized cancer in a patient who declines surgery
Participant is able to provide endoscopic research biopsies and research blood
Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, as assessed within 7 days prior to treatment initiation
A male participant must agree to use a contraception during the treatment period and for at least 120 days, corresponding to time needed to eliminate any study treatment(s) after the last dose of study treatment and refrain from donating sperm during this period
A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
Not a woman of childbearing potential (WOCBP) OR
A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days/weeks after the last dose of study treatment
Patients with stable brain metastasis and/or carcinomatous leptomeningeal disease as defined in exclusion criteria
The participant (or legally acceptable representative if applicable) provides written informed consent for the trial. The participant may also provide consent for future biomedical research. However, the participant may participate in the main trial without participating in future biomedical research
Absolute neutrophil count >= 1500/uL (within 10 days prior to the start of study treatment)
Platelets >= 100 000/uL (within 10 days prior to the start of study treatment)
Hemoglobin >= 9.0 g/dL or >= 5.6 mmol/L (within 10 days prior to the start of study treatment)
Criteria may be met with blood transfusion as these tumors are losing blood
Creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated* creatinine clearance (CrCl) >= 60 mL/min for participant with creatinine levels > 1.5 x institutional ULN (within 10 days prior to the start of study treatment) (GFR can also be used in place of creatinine or CrCl)
Creatinine clearance (CrCl) should be calculated per institutional standard
Total bilirubin =<1.5 x ULN OR direct bilirubin =< ULN for participants with total bilirubin levels > 1.5 x ULN (within 10 days prior to the start of study treatment)
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN (within 10 days prior to the start of study treatment)
International normalized ratio (INR) OR prothrombin time (PT), activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants (within 10 days prior to the start of study treatment)

You may not qualify if…

Has cancer that is confined to the stomach and not involving gastroesophageal junction
Has significant cardiovascular impairment within 6 months of the first dose of study drug (New York Heart Association [NYHA] class III or IV)
Has had major surgery, open biopsy, or significant traumatic injury within 28 days prior to randomization, or anticipation of the need for major surgery during the course of study treatment
Note: If participant has had major surgery, they must have recovered adequately from the toxicity and/or complications from the treatment prior to starting study intervention
Has pre-existing peripheral neuropathy > grade 1
Participant has a history of (non-infectious) pneumonitis that required treatment with steroids or currently has pneumonitis
Participant has a known additional malignancy that is progressing or has required active treatment in the last 2 years
Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, ductal carcinoma in situ, or cervical carcinoma in situ that has undergone potentially curative therapy are not excluded
Participant has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
Note: Participants with previously treated brain metastases may participate provided they are radiologically stable (i.e., without evidence of progression for at least 4 weeks by repeat imaging [repeat imaging should be performed during study screening]), clinically stable, and without requirement for steroid treatment for at least 14 days prior to the first dose of study treatment
Participant has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
Participant has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs)
Note: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment
Participant has an active infection requiring systemic therapy
Participant has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's involvement for the full duration of the trial, or is not in the best interest of the participant to be involved, in the opinion of the treating investigator
Note: Participants who received colony-stimulating factors (e.g., granulocyte colony stimulating factor [G-CSF], granulocyte macrophage colony-stimulating factor [GM-CSF] or recombinant erythropoietin) within 2 weeks prior to the first dose of study treatment are not eligible
Participant has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
Participant has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority
Participant has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as HCV ribonucleic acid [RNA] [qualitative] is detected) infection. No testing for hepatitis B or hepatitis C is required
Participant has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T cell receptor (e.g., CTLA-4, OX 40, CD137)
Participant has received prior systemic anti-cancer therapy including investigational agents
Has received prior radiotherapy for the current disease
Participant has received a live vaccine within 30 days prior to the first dose of study treatment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed
Participant has severe hypersensitivity (>= grade 3) to pembrolizumab or any of its excipients
Participant is currently participating in or has participated in a study of an investigational agent (anti-cancer agent only) or has used an investigational device within 4 weeks prior to the first dose of study treatment

Where it is running

M D Anderson Cancer Center — Houston, Texas, United States

Full record on ClinicalTrials.gov

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