Neoplasms

All Conditions

Digestive System Diseases

Symptoms and General Pathology

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Adenocarcinoma

Stomach Neoplasms

Recurrence

Esophageal Squamous Cell Carcinoma

Esophageal Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Neoplasms, Squamous Cell

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Diseases

Head and Neck Neoplasms

Esophageal Diseases

Stomach Cancer

Esophageal Cancer

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Vitamins

Oxaliplatin

10-deazaaminopterin

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Enzyme Inhibitors

Folinic Acid

Folate

Vitamin B9

Patients receive pralatrexate IV over 3-5 minutes and oxaliplatin IV over 2 hours on day 1. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. Oxaliplatin will be discontinued after 12 courses.

Laboratory Biomarker Analysis

Pralatrexate

Nikhil Khushalani

This phase II trial studies how well pralatrexate and oxaliplatin work in treating patients with esophageal, stomach, or gastroesophageal junction cancer that cannot be removed by surgery or has spread from the primary site (place where it started) to other places in the body. Pralatrexate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as oxaliplatin, 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 pralatrexate with oxaliplatin may be an effective treatment for esophageal, stomach, or gastroesophageal junction cancer.

PRIMARY OBJECTIVES:

I. To determine the overall response rate in patients with advanced esophago-gastric cancer (EGC) to combination pralatrexate and oxaliplatin.

SECONDARY OBJECTIVES:

I. To examine the toxicity and tolerability of this regimen. II. To determine the time-to-progression and overall survival using this regimen.

III. To examine whether functionally relevant polymorphisms of genes of the folate metabolism pathway correlate with efficacy and toxicity of pralatrexate.

IV. To examine whether response to pralatrexate can be predicted by micro-ribonucleic acid (microRNA) expression profiling of the epithelial component of the tumor.

OUTLINE:

Patients receive pralatrexate intravenously (IV) over 3-5 minutes and oxaliplatin IV over 2 hours on day 1. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. Oxaliplatin will be discontinued after 12 courses.

After completion of study treatment, patients are followed up for 30 days and then periodically thereafter for up to 5 years.

Pralatrexate and Oxaliplatin in Treating Patients With Unresectable or Metastatic Esophageal, Stomach, or Gastroesophageal Junction Cancer

Pralatrexate in Combination With Oxaliplatin in Advanced Esophago-gastric Cancer: A Phase II Trial With Predictive Molecular Correlates

Kaplan-Meier estimates of median survival time for each genotype

Mean microRNAs expression of mi-215-5p in tumor tissues of responders and non-responders using a microfabricated device called a gene chip.

Overall response rate to combination pralatrexate and oxaliplatin as assessed by Response Evaluation Criteria in Solid Tumors version 1.1. Objective responses will be confirmed 4 weeks after first documentation of response. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Number of participants with an adverse event. Please refer to the adverse event reporting for more detail. Incidence of toxicity as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

Estimated using the Kaplan-Meier method and proportional hazards models.

National Cancer Institute (NCI)

National Comprehensive Cancer Network

Roswell Park Cancer Institute

Patients receive pralatrexate IV over 3-5 minutes and oxaliplatin IV over 2 hours on day 1. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. Oxaliplatin will be discontinued after 12 courses.

Laboratory Biomarker Analysis: Correlative studies

Oxaliplatin: Given IV

Pralatrexate: Given IV

Treatment (Pralatrexate, Oxaliplatin)

Age, Continuous

Sex: Female, Male

Senior Administrator, Compliance - Clinical Research Services

All Cohort -1 treated and eligible patients

Overall Response Rate

Number of Participants With an Adverse Event

Overall Survival (OS)

Time to Progression (TTP)

Overall Survival (OS) for SNP ATIC/AICART - s10932606 Genotypes

Comparison is CR+PR vs stable disease/progression

Responders: CR+PR

Non responders: stable disease/progression

All treated participants that had enough tissue to perform microdissection to collect epithelial cells for subsequent microRNA profiling.

MicroRNA Expression - miR-215-5p

Overall Study

Carcinoma, Hepatocellular

Anus Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Liver Neoplasms

Liver Diseases

Rectal Neoplasms

Anus Diseases

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pralatrexate and Oxaliplatin in Treating Patients With Unresectable or Metastatic Esophageal, Stomach, or Gastroesophageal Junction Cancer	NCT01178944	Adenocarcinoma ... Esophageal Undi... Gastric Adenoca... Gastric Squamou... Recurrent Esoph... Recurrent Esoph... Recurrent Gastr... Stage IIIB Esop... Stage IIIB Esop... Stage IIIB Gast... Stage IIIC Esop... Stage IIIC Esop... Stage IIIC Gast... Stage IV Esopha... Stage IV Esopha... Stage IV Gastri... Undifferentiate...	Laboratory Biom... Oxaliplatin Pralatrexate	18 Years -	Roswell Park Cancer Institute
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
Pralatrexate and Oxaliplatin in Treating Patients With Unresectable or Metastatic Esophageal, Stomach, or Gastroesophageal Junction Cancer	NCT01178944	Adenocarcinoma ... Esophageal Undi... Gastric Adenoca... Gastric Squamou... Recurrent Esoph... Recurrent Esoph... Recurrent Gastr... Stage IIIB Esop... Stage IIIB Esop... Stage IIIB Gast... Stage IIIC Esop... Stage IIIC Esop... Stage IIIC Gast... Stage IV Esopha... Stage IV Esopha... Stage IV Gastri... Undifferentiate...	Laboratory Biom... Oxaliplatin Pralatrexate	18 Years -	Roswell Park Cancer Institute

Spots Global Cancer Trial Database for stage iv esophageal adenocarcinoma