Ignite Creation Date:
2025-12-25 @ 1:45 AM
Ignite Modification Date:
2026-02-17 @ 5:27 PM
Study NCT ID:
NCT02830594
Status:
COMPLETED
Last Update Posted:
2024-02-20
First Post:
2016-05-18
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Pembrolizumab and Palliative Radiation Therapy in Treating Patients With Metastatic Esophagus, Stomach, or Gastroesophageal Junction Cancer
Sponsor:
City of Hope Medical Center
Organization:
Study Overview
Official Title:
Combining Pembrolizumab and Palliative Radiotherapy in Gastroesophageal Cancer to Enhance Anti-Tumor T Cell Response and Augment the Abscopal Effect
Status:
COMPLETED
Status Verified Date:
2024-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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.
Detailed Description:
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.
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.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: