Radiation Therapy for the Treatment of Metastatic Gastrointestinal Cancers

University of California San Francisco (UCSF)

Status: Enrolling

Conditions: Stage IVC Colorectal Cancer AJCC v8; Postneoadjuvant Therapy Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8; Metastatic Malignant Digestive System Neoplasm; Stage IV Esophageal Squamous Cell Carcinoma; Stage IV Gastric Cancer; Stage IVB Gastric Cancer; Pathologic Stage IVA Esophageal Squamous Cell Carcinoma AJCC v8; Postneoadjuvant Therapy Stage IV Esophageal Squamous Cell Carcinoma AJCC v8; Pathologic Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8; Metastatic Hepatocellular Carcinoma; Metastatic Gastroesophageal Junction Adenocarcinoma; Postneoadjuvant Therapy Stage IVB Esophageal Squamous Cell Carcinoma AJCC V8; Stage IVA Hepatocellular Carcinoma AJCC v8; Stage IV Esophageal Adenocarcinoma; Stage IVB Gastroesophageal Junction Adenocarcinoma; Stage IVB Hepatocellular Carcinoma AJCC v8; Stage IV Hepatocellular Carcinoma AJCC v8; Postneoadjuvant Therapy Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8; Stage IVA Esophageal Adenocarcinoma; Stage IV Anal Cancer AJCC v8; Stage IVA Adenocarcinoma of the Gastroesophageal Junction; Postneoadjuvant Therapy Stage IV Gastric Cancer AJCC v8; Pathologic Stage IV Gastric Cancer AJCC v8; Stage IVB Esophageal Squamous Cell Carcinoma; Metastatic Colorectal Carcinoma; Postneoadjuvant Therapy Stage IVA Esophageal Adenocarcinoma AJCC v8; Metastatic Esophageal Carcinoma; Stage IVA Gastric Cancer; Postneoadjuvant Therapy Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8; Metastatic Anal Canal Carcinoma; Stage IVA Colorectal Cancer AJCC v8; Pathologic Stage IVB Esophageal Squamous Cell Carcinoma AJCC v8; Metastatic Gastric Carcinoma; Stage IVB Colorectal Cancer AJCC v8; Pancreatobiliary Carcinoma; Stage IV Colorectal Cancer AJCC v8; Stage IVB Esophageal Adenocarcinoma; Postneoadjuvant Therapy Stage IVB Esophageal Adenocarcinoma AJCC v8; Stage IV Adenocarcinoma of the Gastroesophageal Junction; Pathologic Stage IVB Esophageal Adenocarcinoma AJCC v8; Stage IVA Esophageal Squamous Cell Carcinoma; Pathologic Stage IVA Esophageal Adenocarcinoma AJCC v8; Postneoadjuvant Therapy Stage IVA Esophageal Squamous Cell Carcinoma AJCC v8; Metastatic Small Intestinal Carcinoma

Treatments: Radiation: Radiation Therapy (RT)

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04221893

19721

NCI-2019-08355 (Registry Identifier)

Details and patient eligibility

About

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.

Full description

PRIMARY OBJECTIVE:

I. 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:

I. 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:

I. 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.

Enrollment: 28 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patients must have a histologically, cytologically, or radiographically confirmed metastatic gastrointestinal (GI) malignancy (esophageal, gastroesophageal, gastric, small intestine, hepatocellular, pancreaticobiliary, colorectal, or anal cancer).

2. Patients must be receiving immunotherapy (checkpoint inhibitor or CTLA4 inhibitor) with overall response of progressive disease by RECIST criteria.

3. 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).

4. 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

5. Evaluation by a radiation oncologist within 28 days of study registration.

6. Must have adequate organ function to administer radiation therapy and immunotherapy as per standard of care.

7. Age >= 18 years.

8. Life expectancy exceeding 6 months.

9. Eastern Cooperative Oncology Group (ECOG) 0-2 or Karnofsky performance status >= 50.

10. 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.

    a. If a woman is of child-bearing potential, a negative pregnancy test within 28 days prior to study enrollment is required.

11. Ability to understand a written informed consent document, and the willingness to sign it.

Exclusion criteria

1. Enrollment on immunotherapy clinical trial for which radiation therapy is not permitted.
2. Administration of radiation therapy within 4 weeks prior to study enrollment.
3. Treatment with systemic corticosteroids or other immunosuppressive medications which would significantly diminish the effect of immunotherapy as judged by the treating physician.
4. Radiation therapy is contraindicated as adjudicated by the radiation oncologist.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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28 participants in 1 patient group

Radiation therapy (RT)

Experimental group

Description:

Patients undergo radiation therapy for a total of 5 treatments over 5-9 calendar days in the absence of disease progression or unacceptable toxicity. Target prescription dose will be 30 Gy in 5 fractions and each treatment site (up to 5) will undergo standard Department-approved treatment planning, quality-assurance, and delivery protocols

Treatment:

Radiation: Radiation Therapy (RT)