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Esophageal Squamous Cell Carcinoma

Esophageal Neoplasms

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Neoplasms, Squamous Cell

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Oxaliplatin

10-deazaaminopterin

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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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
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
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 undifferentiated gastric carcinoma