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

Neoplasm Metastasis

Disease Attributes

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Albumin-Bound Paclitaxel

Carboplatin

Fluorouracil

Capecitabine

Cisplatin

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Patients receive cisplatin IV over 1-4 hours on day 1 and fluorouracil IV continuously over 24 hours on days 1-4. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. Patients with complications associated with the central venous access which prevent further infusion of fluorouracil and only after discussion with the Chief Investigator receive capecitabine BID on days 1-4.

Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis

Quality-of-Life Assessment

Cathy Eng

This randomized phase II trial studies how well cisplatin and fluorouracil work compared with carboplatin and paclitaxel in treating patients with anal cancer that cannot be removed by surgery, has come back at or near the same place as the primary tumor, or spread to other places in the body. Drugs used in chemotherapy, such as cisplatin, fluorouracil, 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. It is not yet known whether cisplatin and fluorouracil are more effective than carboplatin and paclitaxel in treating anal cancer.

PRIMARY OBJECTIVES:

I. To evaluate best overall response rate (ORR).

SECONDARY OBJECTIVES:

I. Overall survival (OS). II. Progression free survival (PFS). III. Disease control rate (DCR) (stable disease \[SD\] or better) at 12 and 24 weeks.

IV. Best ORR of non-irradiated lesions. V. Anti-tumor activity and magnitude of response as captured by waterfall plot analyses.

VI. Toxicity. VII. Quality of life (QOL). VIII. Feasibility of conducting a multicenter international study on squamous cell carcinoma of the anus (SCCA) and recruit within a reasonable time frame.

TERTIARY OBJECTIVES:

I. Explorative biomarker analysis.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive cisplatin intravenously (IV) over 1-4 hours on day 1 and fluorouracil IV continuously over 24 hours on days 1-4. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. Patients with complications associated with the central venous access which prevent further infusion of fluorouracil and only after discussion with the Chief Investigator may receive capecitabine twice daily (BID) on days 1-4.

ARM B: Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 12 weeks.

Cisplatin and Fluorouracil Compared With Carboplatin and Paclitaxel in Treating Patients With Inoperable Locally Recurrent or Metastatic Anal Cancer

InterAACT - An International Multicentre Open Label Randomised Phase II Advanced Anal Cancer Trial Comparing Cisplatin Plus 5-Fluorouracil Versus Carboplatin Plus Weekly Paclitaxel in Patients With Inoperable Locally Recurrent or Metastatic Disease

Multivariate analyses will be performed to evaluate the effect of known prognostic factors and biomarkers on outcomes observed.

The ORR will be summarized as the percentage (including 95% confidence intervals) of responders and presented by treatment group and will be compared (as exploratory endpoint) between treatment groups using a chi-squared test.

Anti-tumor activity and magnitude of response will be captured by waterfall plot analyses. The percentage change in tumor size from baseline to the time of best response will be plotted by patients (ordered from worst to best) and bars colored according to best response.

The ORR of non-irradiated lesions will be summarized as the percentage (including 95% confidence intervals) of responders and presented by treatment group and will be compared (as exploratory endpoint) between treatment groups using a chi-squared test.

QOL will be evaluated using the European Organization for Research and Treatment of Cancer Core Quality of Life and EuroQOL-5 dimension-5 level questionnaires. Differences from baseline will be compared between arms of the study using the two sample t-test or Wilcoxon non-parametric method as appropriate.

DCR will be summarized as the percentage (including 95% confidence intervals) of responders and presented by treatment group and will be compared (as exploratory endpoint) between treatment groups using a chi-squared test.

The proportion of centers engaging will be presented with 95% confidence intervals.

The recruitment rate will be calculated overall centers and by country and center.

The Kaplan Meier estimates of OS over time and median OS with associated 95% confidence intervals will be presented by treatment and (as exploratory endpoint) compared using a log rank test. Cox multivariate regression analysis will be used (as exploratory analysis) to calculate the hazard ratio between treatments along with its 95% confidence interval. The treatment effect will be adjusted for the stratification factors and other identified prognostic factors (e.g. time to disease relapse \& whether pre-treated with platinum) in a multivariate setting.

The Kaplan Meier estimates of PFS over time and median PFS with associated 95% confidence intervals will be presented by treatment and (as exploratory endpoint) compared using a log rank test. Cox multivariate regression analysis will be used (as exploratory analysis) to calculate the hazard ratio between treatments along with its 95% confidence interval. The treatment effect will be adjusted for the stratification factors and other identified prognostic factors (e.g. time to disease relapse \& whether pre-treated with platinum) in a multivariate setting.

The proportion of patients experiencing grade 3-5 toxicity will be compared on a regimen basis using the chi-squared test. Fisher's exact test will be used when expected cell frequencies are \< 5.

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
Cisplatin and Fluorouracil Compared With Carboplatin and Paclitaxel in Treating Patients With Inoperable Locally Recurrent or Metastatic Anal Cancer	NCT02560298	Anal Basaloid C... Anal Canal Cloa... Anal Squamous C... Metastatic Anal... Recurrent Anal ... Stage IIIB Anal... Stage IV Anal C...	Capecitabine Carboplatin Cisplatin Fluorouracil Laboratory Biom... Paclitaxel Quality-of-Life...	18 Years -	Eastern Cooperative Oncology Group

Spots Global Cancer Trial Database for metastatic anal canal carcinoma