Neoplasms

Digestive System Diseases

All Conditions

Rare Diseases

Esophageal Neoplasms

Adenocarcinoma

Stomach Neoplasms

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Diseases

Esophageal Cancer

Stomach Cancer

Antineoplastic Agents

All Drugs and Chemicals

Fluorouracil

Capecitabine

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Participants receive fluorouracil and capecitabine per instructions of the treating physician in the absence of disease progression or unacceptable toxicity.

Participants receive fluorouracil and capecitabine and undergo RT per instructions of the treating physician in the absence of disease progression or unacceptable toxicity. Participants may also undergo surgery to some or all of the remaining sites of disease as is clinically prudent and indicated by treating physician.

Patients will receive 5-fluorouracil (5-FU) and capecitabine as maintenance chemotherapy.

Chemotherapy

Conventional Surgery

Radiation Therapy

Quynh Nhu Nguyen, MD

Quynh-Nhu Nguyen

This phase II trial studies how well chemotherapy with or without radiation or surgery works in treating participants with esophageal or gastric cancer that has spread to less than 3 places in the body (oligometastatic). Drugs used in chemotherapy, such as fluorouracil and capecitabine, 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. Surgery, such as complete surgical resection, may stop the spread of tumor cells by surgically removing organs or tumors. Giving chemotherapy with radiation or surgery may work better than chemotherapy alone in treating participants with oligometastatic esophageal or gastric cancer.

PRIMARY OBJECTIVES:

I. To evaluate whether esophageal or gastric patients with oligometastatic cancer without disease progression after first line chemotherapy therapy will demonstrate improved overall survival (OS) with early local therapy (concurrent chemotherapy/radiation and surgery).

SECONDARY OBJECTIVES:

I. Assess the relationships between progression-free survival and overall survival between both treatment arms.

II. Report local control, loco-regional control. III. Report time to progression of distant metastases. IV. Report toxicity.

OUTLINE:

Participants receive induction chemotherapy for a minimum of 6 cycles and a maximum of 8 cycles in the absence of disease progression or unacceptable toxicity. Participants are then randomized to 1 of 2 groups.

GROUP I (MAINTENANCE CHEMOTHERAPY): Participants receive fluorouracil and capecitabine per instructions of the treating physician in the absence of disease progression or unacceptable toxicity.

GROUP II (LOCAL THERAPY): Participants receive fluorouracil and capecitabine and undergo radiation therapy (RT) per instructions of the treating physician in the absence of disease progression or unacceptable toxicity. Participants may also undergo surgery to some or all of the remaining sites of disease as is clinically prudent and indicated by treating physician.

After completion of study treatment, participants are followed up at 4-8 weeks, 2-3 months, every 3-6 months for up to 3 years, and then every 6-12 months thereafter.

Chemotherapy With or Without Radiation or Surgery in Treating Participants With Oligometastatic Esophageal or Gastric Cancer

A Randomized Trial Comparing Early Local Chemoradiation Therapy +/- Surgery Versus Systemic Therapy for Patients With Esophageal or Gastric Cancer With Oligometastases

To be analyzed by Bayesian piecewise regression to assess their relationships with treatment arm and prognostic covariates.

OS distributions in the two arms will be estimated by the method of Kaplan and Meier. Bayesian piecewise exponential regression will be used to assess the relationships between each of OS and PFS, and patients' covariates and treatment arm.

PFS distributions in the two arms will be estimated by the method of Kaplan and Meier. Bayesian piecewise exponential regression will be used to assess the relationships between each of OS and PFS, and patients' covariates and treatment arm.

Graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Carcinoma, Squamous Cell

Esophageal Squamous Cell Carcinoma

Neoplasms, Squamous Cell

Head and Neck Neoplasms

Esophageal Diseases

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

INITIAL TREATMENT: Patients undergo palliative external beam RT daily. On day 1, patients undergo the first RT fraction and then receive pembrolizumab intravenously (IV) over 30 minutes. Cycles repeat every 3 weeks for up to 35 cycles in the absence of disease progression or unacceptable toxicity.

SECOND PHASE: Patients who achieve a complete response, stop study treatment, and then experience radiographic disease progression may be eligible for the second phase at the discretion of the investigator if no cancer treatment was administered since the last dose of pembrolizumab and trial eligibility safety parameters are met. Patients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 3 weeks for up to 17 cycles in the absence of disease progression or unacceptable toxicity.

Undergo palliative external beam radiation therapy

External Beam Radiation Therapy

Laboratory Biomarker Analysis

Marwan Fakih

This phase II trial studies how well pembrolizumab and palliative radiation therapy works in treating patients with esophagus, stomach, or gastroesophageal junction cancer that has spread to other parts of the body. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Palliative radiation therapy, such as external beam radiation therapy, uses high energy beams to treat symptoms that are caused by tumors. Giving pembrolizumab together with palliative radiation therapy may work better in treating patients with esophagus, stomach, or gastroesophageal junction cancer that has spread to other parts of the body.

PRIMARY OBJECTIVE:

I. To establish that the combination of pembrolizumab and traditional external beam multifractionated radiation therapy (RT) to the primary tumor or a single target metastatic site of patients with metastatic gastric, esophageal, and/or gastroesophageal junction (GEJ) cancers will lead to an increase in tumor infiltrating cytotoxic T-cells and circulating cytotoxic T cells and a reduction in immunosuppressive regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) in metastatic sites.

SECONDARY OBJECTIVES:

I. To establish that the combination of pembrolizumab and RT is feasible in the patient population and evaluate toxicities per National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version (ver.) 4.03.

II. To evaluate overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and immune related (ir)RECIST in this treatment population and correlate with tumor T-cell response.

III. To evaluate progression-free (PFS) and overall survival (OS) in this treatment population.

EXPLORATORY OBJECTIVES:

I. To measure changes in whole genome serum micro ribonucleic acid (miRNA) signature before and after protocol therapy and correlate with tumor/immune/stromal cell miRNA expression profiling determined by deep sequencing.

II. To measures changes in fecal and oral microbiomic diversity and correlative with ORR, PFS, and OS.

III. To assess germline mutations in a panel of miRNA regulatory genes using the MiraDx assay as predictors of response and toxicity to pembrolizumab and RT.

OUTLINE:

INITIAL TREATMENT: Patients undergo palliative external beam RT daily. On day 1, patients undergo the first RT fraction and then receive pembrolizumab intravenously (IV) over 30 minutes. Cycles repeat every 3 weeks for up to 35 cycles in the absence of disease progression or unacceptable toxicity.

SECOND PHASE: Patients who achieve a complete response, stop study treatment, and then experience radiographic disease progression may be eligible for the second phase at the discretion of the investigator if no cancer treatment was administered since the last dose of pembrolizumab and trial eligibility safety parameters are met. Patients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 3 weeks for up to 17 cycles in the absence of disease progression or unacceptable toxicity.

After completion of treatment, patients are followed up at 30 days, every 6 weeks for 1 year, and then every 9 and 12 weeks for up to 2 years.

Pembrolizumab and Palliative Radiation Therapy in Treating Patients With Metastatic Esophagus, Stomach, or Gastroesophageal Junction Cancer

Combining Pembrolizumab and Palliative Radiotherapy in Gastroesophageal Cancer to Enhance Anti-Tumor T Cell Response and Augment the Abscopal Effect

Multicolor immunofluorescence was performed to quantitate analogous CPS expression in pre- and posttreatment biopsies. Difference in MIDS expression between pre- and posttreatment was tested using a Paired T-test.

Multicolor immunofluorescence was performed to quantitate analogous TPS expression in pre- and posttreatment biopsies. Difference in MIDS expression between pre- and posttreatment was tested using a Paired T-test.

Multicolor immunofluorescence was performed to quantitate analogous MIDS expression in pre- and posttreatment biopsies. Difference in MIDS expression between pre- and posttreatment was tested using a Paired T-test.

Graded per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Adverse events with incidence greater than 10%. An adverse event is any untoward medical experience or change of an existing condition that occurs during or after treatment, whether or not it is considered to be related to the protocol intervention. Serious Adverse Events as: Death; Is life-threatening experience (places the subject at immediate risk of death from the event as it occurred); Unplanned hospitalization (equal to or greater than 24 hours) or prolongation of existing hospitalization; A persistent or significant disability/incapacity; A congenital anomaly/birth defect; Secondary malignancy; Any other adverse event that, based upon appropriate medical judgment, may jeopardize the subject's health and may require medical or surgical intervention to prevent one of the outcomes listed above.

Response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and immune related (ir)RECIST. Overall Response (OR) = CR + PR.

Estimated using the product-limit method of Kaplan and Meier. Event defined as progression or death from any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. irPD defined as a minimum 20% increase and minimum 5 mm absolute increase in TMTB compared to nadir, or irPD for non-target or new non-measurable lesions. Confirmation of progression is recommended minimum 4 weeks after the first irPD assessment.

Estimated using the product-limit method of Kaplan and Meier. Event defined as death from any cause.

City of Hope Medical Center

"Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.

INITIAL TREATMENT: Patients undergo palliative external beam RT daily. On day 1, patients undergo the first RT fraction and then receive pembrolizumab intravenously (IV) over 30 minutes. Cycles repeat every 3 weeks for up to 35 cycles in the absence of disease progression or unacceptable toxicity.

SECOND PHASE: Patients who achieve a complete response, stop study treatment, and then experience radiographic disease progression may be eligible for the second phase at the discretion of the investigator if no cancer treatment was administered since the last dose of pembrolizumab and trial eligibility safety parameters are met. Patients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 3 weeks for up to 17 cycles in the absence of disease progression or unacceptable toxicity.

External Beam Radiation Therapy: Undergo palliative external beam radiation therapy

Laboratory Biomarker Analysis: Correlative studies

Pembrolizumab: Given IV

Treatment (Pembrolizumab, RT)

Age, Continuous

Sex: Female, Male

Race/Ethnicity, Customized

United States

Region of Enrollment

Paul Frankel, Ph.D.

One patient did not undergo any biopsies due to site of metastasis not being visualized under image guidance and 2 patients did not undergo the second biopsy for patient safety. Four patients had posttreatment biopsies without any viable cancer cells but only residual stromal tissue.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Chemotherapy With or Without Radiation or Surgery in Treating Participants With Oligometastatic Esophageal or Gastric Cancer	NCT03161522	Gastric Adenoca... Oligometastasis Stage IV Esopha... Stage IV Esopha... Stage IV Gastri...	Capecitabine Chemotherapy Conventional Su... Fluorouracil Radiation Thera...	18 Years - 79 Years	M.D. Anderson Cancer Center
Pembrolizumab and Palliative Radiation Therapy in Treating Patients With Metastatic Esophagus, Stomach, or Gastroesophageal Junction Cancer	NCT02830594	Gastric Adenoca... Gastric Squamou... Gastroesophagea... Metastatic Mali... Stage IV Esopha... Stage IV Esopha...	External Beam R... Laboratory Biom... Pembrolizumab	18 Years -	City of Hope Medical Center
Chemotherapy With or Without Radiation or Surgery in Treating Participants With Oligometastatic Esophageal or Gastric Cancer	NCT03161522	Gastric Adenoca... Oligometastasis Stage IV Esopha... Stage IV Esopha... Stage IV Gastri...	Capecitabine Chemotherapy Conventional Su... Fluorouracil Radiation Thera...	18 Years - 79 Years	M.D. Anderson Cancer Center
Chemotherapy With or Without Radiation or Surgery in Treating Participants With Oligometastatic Esophageal or Gastric Cancer	NCT03161522	Gastric Adenoca... Oligometastasis Stage IV Esopha... Stage IV Esopha... Stage IV Gastri...	Capecitabine Chemotherapy Conventional Su... Fluorouracil Radiation Thera...	18 Years - 79 Years	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for stage iv esophageal adenocarcinoma ajcc v7