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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01178944
Recruitment Status : Completed
First Posted : August 10, 2010
Results First Posted : December 13, 2017
Last Update Posted : December 13, 2017
National Cancer Institute (NCI)
National Comprehensive Cancer Network
Information provided by (Responsible Party):
Roswell Park Cancer Institute

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Adenocarcinoma of the Gastroesophageal Junction Esophageal Undifferentiated Carcinoma Gastric Adenocarcinoma Gastric Squamous Cell Carcinoma Recurrent Esophageal Adenocarcinoma Recurrent Esophageal Squamous Cell Carcinoma Recurrent Gastric Carcinoma Stage IIIB Esophageal Adenocarcinoma Stage IIIB Esophageal Squamous Cell Carcinoma Stage IIIB Gastric Cancer Stage IIIC Esophageal Adenocarcinoma Stage IIIC Esophageal Squamous Cell Carcinoma Stage IIIC Gastric Cancer Stage IV Esophageal Adenocarcinoma Stage IV Esophageal Squamous Cell Carcinoma Stage IV Gastric Cancer Undifferentiated Gastric Carcinoma Other: Laboratory Biomarker Analysis Drug: Oxaliplatin Drug: Pralatrexate Phase 2

Detailed Description:


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


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.


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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 35 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pralatrexate in Combination With Oxaliplatin in Advanced Esophago-gastric Cancer: A Phase II Trial With Predictive Molecular Correlates
Study Start Date : September 2010
Actual Primary Completion Date : January 2015
Actual Study Completion Date : November 2015

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Treatment (pralatrexate, oxaliplatin)
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.
Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Oxaliplatin
Given IV
Other Names:
  • 1-OHP
  • Dacotin
  • Dacplat
  • Diaminocyclohexane Oxalatoplatinum
  • Eloxatin
  • Eloxatine
  • JM-83
  • Oxalatoplatin
  • Oxalatoplatinum
  • RP 54780
  • RP-54780
  • SR-96669

Drug: Pralatrexate
Given IV
Other Names:
  • 10-propargyl-10-deazaaminopterin
  • Folotyn
  • PDX

Primary Outcome Measures :
  1. Overall Response Rate [ Time Frame: Up to 5 years ]
    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.

Secondary Outcome Measures :
  1. Number of Participants With an Adverse Event [ Time Frame: Up to 30 days after the last dose of study drug(s) ]
    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

  2. Overall Survival (OS) [ Time Frame: From the date of study enrollment to the time of death from any cause, assessed up to 5 years ]
    Estimated using the Kaplan-Meier method and proportional hazards models.

  3. Time to Progression (TTP) [ Time Frame: From the date of study enrollment to the first observation of progressive disease, assessed up to 5 years ]
    Estimated using the Kaplan-Meier method and proportional hazards models.

Other Outcome Measures:
  1. Overall Survival (OS) for SNP ATIC/AICART - s10932606 Genotypes [ Time Frame: From the date of study enrollment up to 5 years ]
    Kaplan-Meier estimates of median survival time for each genotype

  2. MicroRNA Expression - miR-215-5p [ Time Frame: Baseline ]
    Mean microRNAs expression of mi-215-5p in tumor tissues of responders and non-responders using a microfabricated device called a gene chip.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically confirmed carcinoma of the esophagus, stomach or gastro-esophageal junction that is metastatic, or locally advanced and inoperable for cure; histological sub-types permitted include adenocarcinoma, squamous-cell carcinoma, or undifferentiated carcinoma; small-cell carcinoma variant is not eligible
  • No previous systemic therapy for metastatic or recurrent disease; therapy (chemotherapy, radiotherapy, or both) administered in the neo-adjuvant, adjuvant, or definitive setting for previously localized disease is permitted, provided it was completed more than 6 months prior to enrollment; palliative radiotherapy is permitted provided it is completed >= 3 weeks prior to study therapy initiation
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Life expectancy >= 12 weeks
  • Hemoglobin >= 9 g/dl
  • Absolute neutrophil count >= 1500/mm^3
  • Platelet count >= 100,000/mm^3
  • Serum creatinine =< institutional upper limit normal (ULN)
  • Bilirubin =< 1.5 x ULN
  • Transaminases =< 3 x ULN; for documented liver metastases, transaminases up to 5 x ULN is permitted
  • No evidence of >= grade 2 peripheral neuropathy
  • Patients with reproductive potential must be willing to use an adequate contraceptive method (e.g., abstinence, intrauterine device, oral contraceptives, barrier device with spermicide or surgical sterilization) during treatment and for three months after completing treatment; a negative pregnancy test is required for women of child-bearing potential; nursing women are ineligible
  • Written, informed consent

Exclusion Criteria:

  • Hypersensitivity to platinum compounds
  • Uncontrolled inter-current illness including but not limited to active infection, symptomatic congestive heart failure, unstable angina, uncontrolled cardiac arrhythmia, or psychiatric illness that would limit compliance with study requirements
  • Presence of brain metastases
  • Patients with third-space (pleural, peritoneal) fluid not controllable with usual drainage methods are not eligible
  • History of second primary malignancy within 3 years prior to enrollment, except for in-situ cervix carcinoma or non-melanoma skin cancer
  • Undergone an allogeneic stem cell transplant

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01178944

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United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Rochester General Hospital
Rochester, New York, United States, 14621
Sponsors and Collaborators
Roswell Park Cancer Institute
National Cancer Institute (NCI)
National Comprehensive Cancer Network
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Principal Investigator: Nikhil Khushalani Roswell Park Cancer Institute
  Study Documents (Full-Text)

Documents provided by Roswell Park Cancer Institute:
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Responsible Party: Roswell Park Cancer Institute Identifier: NCT01178944    
Other Study ID Numbers: I 169210
NCI-2010-01583 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
I 169210 ( Other Identifier: Roswell Park Cancer Institute )
P30CA016056 ( U.S. NIH Grant/Contract )
First Posted: August 10, 2010    Key Record Dates
Results First Posted: December 13, 2017
Last Update Posted: December 13, 2017
Last Verified: November 2017
Additional relevant MeSH terms:
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Carcinoma, Squamous Cell
Stomach Neoplasms
Esophageal Squamous Cell Carcinoma
Esophageal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Head and Neck Neoplasms
Esophageal Diseases
Antineoplastic Agents
Folic Acid Antagonists
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action