Neoplasms

Digestive System Diseases

All Conditions

Rare Diseases

Esophageal Neoplasms

Carcinoma

Adenocarcinoma

Stomach Neoplasms

Carcinoma, Squamous Cell

Carcinoma, Hepatocellular

Esophageal Squamous Cell Carcinoma

Gastrointestinal Neoplasms

Digestive System Neoplasms

Anus Neoplasms

Colorectal Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Intestinal Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Neoplasms, Squamous Cell

Liver Neoplasms

Liver Diseases

Stomach Diseases

Head and Neck Neoplasms

Esophageal Diseases

Rectal Neoplasms

Anus Diseases

Esophageal Cancer

Stomach Cancer

Anal Cancer

Small Intestine Cancer

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

Radiation Therapy (RT)

Hewitt Chang

Mary Feng, MD

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.

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.

Radiation Therapy for the Treatment of Metastatic Gastrointestinal Cancers

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

Proportion of patients who achieve as their best overall response according to Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1 criteria: Stable disease (SD), partial response (PR), confirmed Complete Response (CR), or progressive disease (PD). Corresponding exact confidence intervals will be reported for the entire cohort and stratified by histologic subtype, programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) status, microsatellite instability (MSI), and organs treated if sample size allows. Patients with unevaluable or unknown response status will be considered nonresponders.

Will be determined by immune-Modified Response Evaluation Criteria in Solid Tumors (iRECIST). Immune Complete Response (iCR), Partial Response (iPR), or Stable Disease (iSD) per definitions of CR, PR, and SD, but occurring after initial immune unconfirmed progressive disease (iUPD). The same definition will be used for per lesion analysis. PD will be designated for all patients with PD determination by RECIST v1.1 or immune-confirmed progressive disease (iCPD) by iRECIST. Unconfirmed response for all patients designated as iUPD. Will be reported as proportion of response and corresponding exact confidence intervals. Patients with unevaluable or unknown response status will be considered nonresponders.

PFS is defined as the duration of time from start of radiation treatment to time of progression or death a proportion with exact confidence intervals and will be reported for the entire cohort and stratified by histologic subtype, PD1/PDL1 status, MSI, and organs treated if sample size allows. Time to local progression will be described using the cumulative incidence method and comparisons between strata via Gray's test, if sample size allows; Otherwise, Kaplan-Meier methodology will be used and comparisons will be made via log-rank test; and Cox proportional hazards analysis, if possible.

OS will be measured from the date of initiation of RT. OS is defined as the time from the date of initiation of RT to the date of death due to any cause. Censoring will be performed using the date of last known contact for those who are alive at the time of analysis. OS will be reported for the entire cohort and stratified by histologic subtype, PD1/PDL1 status, MSI, and organs treated if sample size allows.

Local control will be defined as absence of per-lesion PD in an irradiated lesion (as defined above, a 20% increase in the longest diameter since the treatment started or a 5 mm increase over the nadir longest diameter from initiation of radiation therapy to time of progression of radiated lesion(s)

Abscopal response rate is defined as present for all patients for whom an unirradiated target or non-target lesion previously determined to be a progressing lesion is designated as SD, CR/iCR or PR/iPR on per-lesion analysis will be described as a proportion with exact confidence intervals and will be reported for the entire cohort, reported for RECIST and iRECIST definitions, and stratified by histologic subtype, PD1/PDL1 status, MSI, and organs treated if sample size allows

From initiation of radiation therapy to first imaging scan after radiation therapy completion, time to new metastatic lesions will be described using the cumulative incidence method and comparisons between strata via Gray's test, if sample size allows; Kaplan-Meier methodology will be used and comparisons will be made via log-rank test; and Cox proportional hazards analysis, if possible.

Common Terminology Criteria for Adverse Events (CTCAE v.5.0) will be used to determine frequency of grade 3 or higher adverse events reported as a proportion with corresponding exact confidence intervals.

Time to new systemic therapy from initiation of radiation therapy to initiation of new systemic therapy will be described using Kaplan-Meier product limit estimators, and Cox proportional hazards analysis, if possible.

Varian Medical Systems

University of California, San Francisco

Symptoms and General Pathology

Recurrence

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Carboplatin

Albumin-Bound Paclitaxel

Nivolumab

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients receive paclitaxel IV on days 1, 8, and 15 of each cycle, and carboplatin IV on day 1 of each cycle. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Patients receive nivolumab IV over 30 minutes on days 1 and 15 of cycle 1 and then on day 1 only of subsequent cycles, paclitaxel IV on days 1, 8, and 15 of each cycle, and carboplatin on day 1 of each cycle. Treatment repeats every 28 days for up to 6 cycles for carboplatin and paclitaxel, and up to 2 years for nivolumab in the absence of disease progression or unacceptable toxicity.

Site Public Contact

John A. Ellerton

Shahzad Siddique

Gary L. Buchschacher

Tatjana Kolevska

Syma Iqbal

Jun Gong

Jennifer B. Valerin

Gregory A. Masters

Mohamedtaki A. Tejani

Christopher M. Reynolds

Ranjith B. Dissanayake

Boris Naraev

Josh D. Simmons

Cathy Eng

This phase 3 trial compares the addition of nivolumab to chemotherapy (carboplatin and paclitaxel) versus usual treatment (chemotherapy alone) for the treatment of anal cancer that has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving nivolumab together with carboplatin and paclitaxel may help doctors find out if the treatment is better or the same as the usual approach.

PRIMARY OBJECTIVE:

I. To demonstrate that anti-PD-1 therapy in combination with carboplatin/weekly paclitaxel results in improved progression-free survival (PFS) versus systemic chemotherapy alone.

SECONDARY OBJECTIVES:

I. To demonstrate that anti-PD-1 therapy in combination with carboplatin/weekly paclitaxel results in improved overall survival (OS) versus systemic chemotherapy alone.

II. To demonstrate that anti-PD-1 therapy in combination with carboplatin/weekly paclitaxel results in improved objective response using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 versus systemic chemotherapy alone.

III. To evaluate toxicity profiles of the two regimens.

OUTLINE: Patients are randomized to 1 of 2 arms. Randomization will be 2:1 favoring the experimental regimen, Arm B.

ARM A: Patients receive paclitaxel intravenously (IV) on days 1, 8, and 15 of each cycle, and carboplatin IV on day 1 of each cycle. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive nivolumab IV over 30 minutes on days 1 and 15 of cycle 1 and then on day 1 only of subsequent cycles, paclitaxel IV on days 1, 8, and 15 of each cycle, and carboplatin on day 1 of each cycle. Treatment repeats every 28 days for up to 6 cycles for carboplatin and paclitaxel, and up to 2 years for nivolumab in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 1 month, then every 3 months for 2 years.

EA2176: Phase 3 Clinical Trial of Carboplatin and Paclitaxel +/- Nivolumab in Metastatic Anal Cancer Patients

A Randomized Phase III Study of Immune Checkpoint Inhibition With Chemotherapy in Treatment-Naive Metastatic Anal Cancer Patients

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page

Defined as the first of progressive disease or death due to any cause. Analyzed using a stratified two-sided overall 0.05 level log-rank test. Will utilize standard Eastern Cooperative Oncology Group -American College of Radiology Imaging Network interim monitoring for efficacy evaluation.

ORR is the ratio of the number of patients with a complete response or partial response, as defined by Response Evaluation Criteria in Solid Tumors version 1.1, to the total number of treated patients.

Evaluated by a stratified log-rank test, and using a two-sided 0.05 level Cochran Mantel-Haenzel.

Analyses of toxicity will be via frequency tabulations and percentages by worst degree of toxicity and comparisons will be done via chi-square or Fisher's exact tests as appropriate.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Radiation Therapy for the Treatment of Metastatic Gastrointestinal Cancers	NCT04221893	Stage IV Esopha... Stage IV Esopha... Stage IV Gastri... Stage IV Adenoc... Stage IVA Esoph... Stage IVA Esoph... Stage IVA Gastr... Stage IVA Adeno... Stage IVB Esoph... Stage IVB Esoph... Stage IVB Gastr... Stage IVB Gastr... Metastatic Anal... Metastatic Colo... Metastatic Esop... Metastatic Gast... Metastatic Gast... Metastatic Hepa... Metastatic Mali... Metastatic Smal... Pancreatobiliar... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Stage IV Anal C... Stage IV Colore... Stage IV Hepato... Stage IVA Color... Stage IVA Hepat... Stage IVB Color... Stage IVB Hepat... Stage IVC Color...	Radiation Thera...	18 Years -	University of California, San Francisco
EA2176: Phase 3 Clinical Trial of Carboplatin and Paclitaxel +/- Nivolumab in Metastatic Anal Cancer Patients	NCT04444921	Anal Basaloid S... Anal Canal Cloa... Metastatic Anal... Recurrent Anal ... Stage III Anal ... Stage IV Anal C... Unresectable An...	Carboplatin Nivolumab Paclitaxel	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for stage iv anal cancer ajcc v8