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Gastric AdenocarcinomaPhase 2NCT02830594

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

A Phase 2 study testing External Beam Radiation Therapy, Laboratory Biomarker Analysis and Pembrolizumab in people with Gastric Adenocarcinoma and Gastric Squamous Cell Carcinoma, run by City of Hope Medical Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
External Beam Radiation Therapy, Laboratory Biomarker Analysis and Pembrolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
14 participants
Where
1 siteUnited States
Study dates
13 Dec 2016to 16 Jan 2024
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Documented informed consent of the participant
  • Willing to provide tumor tissue amenable to ultrasound or computed tomography (CT)-guided biopsy for biomarker analyses
  • Patients with malignant ascites are permitted to participate and provide ascites samples for biomarker analyses
  • Patents receiving radiation to a single metastatic site in which only the primary tumor is accessible for biopsy by endoscopy will also be eligible
  • Eastern Cooperative Oncology Group (ECOG) performance status of =< 1
  • Life expectancy of >= 3 months
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  • Diagnosis of metastatic squamous cell carcinoma and/or adenocarcinoma of the esophagus, gastroesophageal junction, or stomach in need of palliative radiotherapy to the primary tumor or a single metastatic site for symptoms such as pain, dysphagia, and/or gastrointestinal bleeding
  • Patients with adenocarcinoma histology and known human epidermal growth factor receptor 2 (HER2) overexpressing disease are permitted to participate if the progressed or are intolerant of prior trastuzumab-containing therapy
  • Measurable metastatic sites of disease outside of the target lesion undergoing palliative radiation based on RECIST 1.1 as assessed by the investigator
  • Have no limits on prior lines of therapy or may be treatment-naive if in need of palliative RT provided the patient has not received prior anti-programmed cell death protein 1(PD-1), anti-programmed cell death 1 ligand 1 (PD-L1), or anti-programmed cell death 1 ligand 2 (PD-L2) therapy
  • Absolute neutrophil count (ANC) >= 1,500/mm^3
  • Platelets >= 100,000/mm^3
  • Hemoglobin >= 9 g/dL
  • May receive transfusion to meet this goal
  • Total serum bilirubin =< 1.5 x upper limit of normal (ULN) OR direct bilirubin =< ULN if total bilirubin levels > 1.5 x ULN
  • Albumin >= 2.5 mg/dL
  • Aspartate aminotransaminase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN OR =< 5.0 x ULN if liver metastases present
  • Serum creatinine =< 1.5 x ULN OR creatinine clearance (if measured or calculated per institutional standard) >= 60 mL/min if creatinine levels > 1.5 x ULN
  • Glomerular filtration rate (GFR) can also be used in place of creatinine or creatinine clearance (CrCl)
  • If not receiving anticoagulants: international normalized ratio (INR) OR prothrombin (PT) =< 1.5 x ULN; if on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants
  • If not receiving anticoagulants: activated partial thromboplastin time (aPTT) =< 1.5 x ULN; if on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants
  • Negative urine or serum pregnancy test (female of childbearing potential only)
  • If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Female of childbearing potential: willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication
  • Childbearing potential defined as not being surgically sterilized or have not been free from menses for > 1 year
  • Male: use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy

Who cannot join

  • Anti-PD-1, anti-PD-L1, or anti-PD-L2 agents
  • Prior radiation therapy within the field of the target lesion that in the opinion of the treating radiation oncologist would preclude further palliative radiation to a dose of 30 gray (Gy)
  • Anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
  • Chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to a previously administered agent
  • Note: Subjects with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study
  • Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
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  • Live vaccine within 30 days of planned start of study therapy
  • Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed
  • Immunosuppressive therapy within 7 days prior to the first dose of trial treatment
  • Investigational device within 4 weeks of the first dose of treatment
  • Currently receiving an investigational agent
  • About to undergo palliative radiation for a symptomatic central nervous system (CNS) metastasis
  • Systemic steroid therapy
  • Hypersensitivity to pembrolizumab or any of its excipients
  • Diagnosis of immunodeficiency
  • 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)
  • Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
  • Known history of, or any evidence of active, non-infectious pneumonitis
  • Current active infection requiring systemic therapy
  • Known history of active tuberculosis (TB), human immunodeficiency virus (HIV) 1/2, hepatitis B or hepatitis C
  • Known additional malignancy that is progressing or requires active treatment
  • Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
  • Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Subjects with previously treated brain metastases may participate provided they are stable, have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
  • History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
  • Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Pregnant or breastfeeding (female only)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • City of Hope Medical Center

    Duarte, California, 91010

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

  1. 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:

  1. 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.

Being tested
External Beam Radiation Therapy, Laboratory Biomarker Analysis, Pembrolizumab
Medical subject headings
Adenocarcinoma Of Esophagus, Esophageal Squamous Cell Carcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • External Beam Radiation TherapyRadiation

    Also called Definitive Radiation Therapy, EBRT, External Beam Radiation, External Beam Radiotherapy

    Undergo palliative external beam radiation therapy

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • PembrolizumabBiological

    Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475

    Given IV

Study groups in NCT02830594
Study groupRoleWhat they receive
Treatment (pembrolizumab, RT)ExperimentalINITIAL 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.
Receives: Radiation: External Beam Radiation Therapy; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Changes in Combined Positive Scoring (CPS) in Non-irradiated Sites Assessed by Flow Cytometry

    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.

    Measured: Baseline to 105 weeks

  2. Changes in Tumor Proportion Scores (TPS) in Non-irradiated Sites Assessed by Flow Cytometry

    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.

    Measured: Baseline to 105 weeks

  3. Changes in Myeloid-derived Suppressor Cells (MDSC) in Non-irradiated Sites Assessed by Flow Cytometry

    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.

    Measured: Baseline to 105 weeks

Secondary outcomes (4)

  1. Incidence of Treatment Related Adverse Events of Pembrolizumab

    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.

    Measured: Up to 36 months

  2. Overall Response Rate (ORR)

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

    Measured: Up to 36 months

  3. Progression-free Survival (PFS)

    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.

    Measured: Up to 36 months

  4. Overall Survival (OS)

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

    Measured: Up to 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jul 2016 (estimated)
  2. Study start13 Dec 2016
  3. Primary completion20 Jan 2022
  4. Study completion16 Jan 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
14 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02830594
Sponsor's protocol ID
16099
Other IDs
NCI-2016-00686, 16099
Status last verified
Oct 2026
First submitted
18 May 2016
Last updated
2 Nov 2026
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing External Beam Radiation Therapy, Laboratory Biomarker Analysis and Pembrolizumab in people with Gastric Adenocarcinoma and Gastric Squamous Cell Carcinoma, run by City of Hope Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Jun 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Changes in Combined Positive Scoring (CPS) in Non-irradiated Sites Assessed by Flow Cytometry (time frame: Baseline to 105 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02830594.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2026; AzTrials last refreshed its copy on 8 Nov 2026.

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