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

NCT02830594 | Completed Phase 2 Results DMC

• 2 other identifiers: 16099NCI-2016-00686
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Gastric Adenocarcinoma; Gastric Squamous Cell Carcinoma; Gastroesophageal Junction Adenocarcinoma; Metastatic Malignant Neoplasm in the Stomach; Stage IV Esophageal Adenocarcinoma AJCC v7; Stage IV Esophageal Squamous Cell Carcinoma AJCC v7

Outcome Measures

Primary Outcomes (3)

• 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.

  Baseline to 105 weeks

• 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.

  Baseline to 105 weeks

• 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.

  Baseline to 105 weeks

Secondary Outcomes (4)

• Incidence of Treatment Related Adverse Events of Pembrolizumab

  Up to 36 months

• Overall Response Rate (ORR)

  Up to 36 months

• Progression-free Survival (PFS)

  Up to 36 months

• Overall Survival (OS)

  Up to 36 months

Study Arms (1)

Treatment (pembrolizumab, RT)

EXPERIMENTAL

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.

Radiation: External Beam Radiation Therapy; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab

Interventions

External Beam Radiation Therapy RADIATION

Undergo palliative external beam radiation therapy

Also known as: Definitive Radiation Therapy, EBRT, External Beam Radiation, External Beam Radiotherapy, External Beam RT, external radiation, External Radiation Therapy, external-beam radiation, Radiation, External Beam

Treatment (pembrolizumab, RT)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (pembrolizumab, RT)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (pembrolizumab, RT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Adenocarcinoma Of Esophagus; Esophageal Squamous Cell Carcinoma

Interventions

Radiation; pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Physical Phenomena

Results Point of Contact

• Title: Paul Frankel, Ph.D.
• Organization: City of Hope

pfrankel@coh.org

626-218-5265

Study Officials

• Marwan Fakih

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2016
• First Posted: July 13, 2016
• Study Start: October 5, 2016
• Primary Completion: January 20, 2022
• Study Completion: January 16, 2024
• Last Updated: February 20, 2024
• Results First Posted: June 30, 2022

Record last verified: 2024-02

Locations

US (1)