Clinical trial NCT04221893: Radiation Therapy for the Treatment of Metastatic Gastrointestinal Cancers
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: 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
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Varian Medical Systems
First posted: 2020-01-09
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Overall response rate (ORR)
timeFrame: Up to 8 weeks
Secondary outcomes:
measure: ORR by immune-Modified Response Evaluation Criteria in Solid Tumors (iRECIST)
timeFrame: Up to 8 weeks
measure: Progression free survival (PFS)
timeFrame: Up to 36 months
measure: Overall survival (OS)
timeFrame: Up to 36 months
measure: Determine local control in radiated lesion(s)
timeFrame: Up to 36 months
measure: Tumor measurement change by RECIST or iRECIST
timeFrame: Up to 8 weeks
measure: Incidence of New metastatic lesions
timeFrame: Up to 8 weeks
measure: Frequency of grade 3 or higher adverse events
timeFrame: Up to 36 months
measure: Time to new systemic therapy
timeFrame: Up to 36 months
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
Study officials:
affiliation: University of California, San Francisco
name: Mary Feng, MD
role: PRINCIPAL_INVESTIGATOR
References: