Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at San Francisco, California
Dates
study started
estimated completion
Principal Investigator
Mary Feng, MD
Photo of Mary Feng
Mary Feng

Description

Summary

This phase II trial studies how well radiation therapy works for the treatment of gastrointestinal cancer that are spreading to other places in the body (metastatic). Radiation therapy uses high energy x-rays to kill cancer cells and shrink tumors. This trial is being done to determine if giving radiation therapy to patients who are being treated with immunotherapy and whose cancers are progressing (getting worse) can slow or stop the growth of their cancers. It may also help researchers determine if giving radiation therapy to one tumor can stimulate the immune system to attack other tumors in the body that are not targeted by the radiation therapy.

Official Title

Phase II Study of Hypofractionated Radiation Therapy to Augment Immune Response in Patients With Metastatic GastroIntestinal Malignancies Progressing on Immune Therapy (ARM-GI)

Details

PRIMARY OBJECTIVE:

  1. To determine whether radiation therapy can convert overall response rates from progressive disease to stable or responsive disease as measured by Response Evaluation Criteria in Solid Tumors (RECIST) version (v.) 1.1.

SECONDARY OBJECTIVES:

  1. To define overall response rate by immune-Modified Response Evaluation Criteria in Solid Tumors (iRECIST) criteria.

II. To determine time to progression. III. To determine overall survival. IV. To determine local control in radiated lesion(s). V. To characterize the effect of distant radiation on unirradiated target lesions.

VI. To describe the incidence of new metastatic lesions. VII. To determine treatment safety by Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0.

VIII. To describe time to new systemic therapy.

EXPLORATORY OBJECTIVES:

  1. To define radiation-induced effects on circulating immune cells. II. To describe remodeling of the circulating T cell repertoire by deep sequencing of variable, diversity and joining (VDJ) regions of T cell receptors (TCRs).

III. To describe changes in circulating tumor deoxyribonucleic acid (DNA) (ctDNA).

OUTLINE:

Patients undergo radiation therapy for a total of 5 treatments over 5-9 calendar days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 14 day, 6 months, and then up to 36 months.

Keywords

Stage IV Esophageal Adenocarcinoma Stage IV Esophageal Squamous Cell Carcinoma Stage IV Gastric Cancer Stage IV Adenocarcinoma of the Gastroesophageal Junction Stage IVA Esophageal Adenocarcinoma Stage IVA Esophageal Squamous Cell Carcinoma Stage IVA Gastric Cancer Stage IVA Adenocarcinoma of the Gastroesophageal Junction Stage IVB Esophageal Adenocarcinoma Stage IVB Esophageal Squamous Cell Carcinoma Stage IVB Gastric Cancer Stage IVB Gastroesophageal Junction Adenocarcinoma Metastatic Anal Canal Carcinoma Metastatic Colorectal Carcinoma Metastatic Esophageal Carcinoma Metastatic Gastric Carcinoma Metastatic Gastroesophageal Junction Adenocarcinoma Metastatic Hepatocellular Carcinoma Metastatic Malignant Digestive System Neoplasm Metastatic Small Intestinal Carcinoma Pancreatobiliary Carcinoma Pathologic Stage IV Gastric Cancer AJCC v8 Pathologic Stage IVA Esophageal Adenocarcinoma AJCC v8 Pathologic Stage IVA Esophageal Squamous Cell Carcinoma AJCC v8 Pathologic Stage IVB Esophageal Adenocarcinoma AJCC v8 Pathologic Stage IVB Esophageal Squamous Cell Carcinoma AJCC v8 Pathologic Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8 Postneoadjuvant Therapy Stage IV Esophageal Squamous Cell Carcinoma AJCC v8 Postneoadjuvant Therapy Stage IV Gastric Cancer AJCC v8 Postneoadjuvant Therapy Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8 Postneoadjuvant Therapy Stage IVA Esophageal Adenocarcinoma AJCC v8 Postneoadjuvant Therapy Stage IVA Esophageal Squamous Cell Carcinoma AJCC v8 Postneoadjuvant Therapy Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8 Postneoadjuvant Therapy Stage IVB Esophageal Adenocarcinoma AJCC v8 Postneoadjuvant Therapy Stage IVB Esophageal Squamous Cell Carcinoma AJCC V8 Postneoadjuvant Therapy Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8 Stage IV Anal Cancer AJCC v8 Stage IV Colorectal Cancer AJCC v8 Stage IV Hepatocellular Carcinoma AJCC v8 Stage IVA Colorectal Cancer AJCC v8 Stage IVA Hepatocellular Carcinoma AJCC v8 Stage IVB Colorectal Cancer AJCC v8 Stage IVB Hepatocellular Carcinoma AJCC v8 Stage IVC Colorectal Cancer AJCC v8 Carcinoma Colorectal Neoplasms Carcinoma, Squamous Cell Adenocarcinoma Carcinoma, Hepatocellular Stomach Neoplasms Esophageal Squamous Cell Carcinoma Esophageal Neoplasms Anus Neoplasms Digestive System Neoplasms Gastrointestinal Neoplasms Radiation Therapy (RT)

Eligibility

You can join if…

Open to people ages 18 years and up

  • Patients must have a histologically, cytologically, or radiographically confirmed metastatic gastrointestinal (GI) malignancy (esophageal, gastroesophageal, gastric, small intestine, hepatocellular, pancreaticobiliary, colorectal, or anal cancer)
  • Patients must be receiving immunotherapy (checkpoint inhibitor or CTLA4 inhibitor) with overall response of progressive disease by RECIST criteria
  • Patients must have at least two metastases which are individually progressing as per RECIST criteria, one of which can be safely unirradiated as adjudicated by the treating radiation oncologist (e.g. lesions for which small increases in dimensions are unlikely to precipitate significant symptoms)
  • Patients must have 1-5 sites of disease meeting standard-of-care indications for palliative radiation therapy as adjudicated by the treating radiation oncologist. For example:
  • Symptomatic disease causing pain, bleeding, dyspnea, dysphagia, or nausea
  • At-risk for neurologic, respiratory, cardiovascular, gastrointestinal, musculoskeletal, or hepatobiliary compromise
  • Evaluation by a radiation oncologist within 28 days of study registration
  • Absolute neutrophil count at least 1,200/microliter (mcL)
  • Platelets at least 75,000/mcL
  • Hemoglobin at least 9 g/dL (unless documented bleeding where at least 8 g/dL is permitted)
  • Total bilirubin less than 2 mg/dL or 1.5 X upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 5 X ULN
  • International normalized ratio (INR) less than 1.5 X ULN unless on anticoagulation therapy
  • Albumin at least 2.8 g/dL
  • Creatinine less than 1.5 X ULN and/or creatinine clearance >= 60 mL/min
  • Life expectancy exceeding 6 months
  • Eastern Cooperative Oncology Group (ECOG) 0-2 or Karnofsky performance status >= 50
  • Radiation therapy is known to be teratogenic and therefore women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of radiation therapy. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study and for 3 months after completion of radiation therapy. Contraception requirements during the follow-up period of 6 months will be according to standard of care for immunotherapy administration.
  • If a woman is of child-bearing potential, a negative pregnancy test within 28 days prior to study enrollment is required
  • Ability to understand a written informed consent document, and the willingness to sign it

You CAN'T join if...

  • Enrollment on immunotherapy clinical trial for which radiation therapy is not permitted
  • Administration of radiation therapy within 4 weeks prior to study enrollment
  • Treatment with systemic corticosteroids or other immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, methotrexate, anti-tumor necrosis factor (TNF) agents, etc) within 2 weeks of enrollment
  • Systemic corticosteroids for adrenal insufficiency is not excluded
  • Systemic corticosteroids for acute asthma, bronchitis, or chronic obstructive pulmonary disease exacerbation (less than 2 weeks in duration) is not excluded
  • Systemic corticosteroids used for short-term purposes (e.g. nausea, anti-inflammatory indications for brain/spinal metastases or radiation-induced pain flares) are not excluded
  • Radiation therapy is contraindicated as adjudicated by the radiation oncologist

Location

  • University of California, San Francisco accepting new patients
    San Francisco California 94143 United States

Lead Scientist at UCSF

  • Mary Feng, MD
    Dr. Mary Feng specializes in treating patients with cancers in the abdomen (gastrointestinal and hepatobiliary). Her approach is to make sure care is compassionate and coordinated. Her research uses advanced biology and technical advances to personalize and adapt radiation treatments for each patient to make treatment the most effective with the least amount of side effects.

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
University of California, San Francisco
ID
NCT04221893
Study Type
Interventional
Last Updated