- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01178944
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
Study Overview
Status
Conditions
- Gastric Adenocarcinoma
- Recurrent Gastric Carcinoma
- Esophageal Undifferentiated Carcinoma
- Gastric Squamous Cell Carcinoma
- Adenocarcinoma of the Gastroesophageal Junction
- Stage IV Gastric Cancer
- Stage IIIB Gastric Cancer
- Stage IIIC Gastric Cancer
- Stage IV Esophageal Adenocarcinoma
- Stage IV Esophageal Squamous Cell Carcinoma
- Stage IIIB Esophageal Adenocarcinoma
- Stage IIIC Esophageal Adenocarcinoma
- Recurrent Esophageal Adenocarcinoma
- Recurrent Esophageal Squamous Cell Carcinoma
- Stage IIIB Esophageal Squamous Cell Carcinoma
- Stage IIIC Esophageal Squamous Cell Carcinoma
- Undifferentiated Gastric Carcinoma
Intervention / Treatment
Detailed Description
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
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New York
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Buffalo, New York, United States, 14263
- Roswell Park Cancer Institute
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Rochester, New York, United States, 14621
- Rochester General Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / 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.
|
Correlative studies
Given IV
Other Names:
Given IV
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
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Up to 5 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
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Up to 30 days after the last dose of study drug(s)
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Overall Survival (OS)
Time Frame: From the date of study enrollment to the time of death from any cause, assessed up to 5 years
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Estimated using the Kaplan-Meier method and proportional hazards models.
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From the date of study enrollment to the time of death from any cause, assessed up to 5 years
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Time to Progression (TTP)
Time Frame: From the date of study enrollment to the first observation of progressive disease, assessed up to 5 years
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Estimated using the Kaplan-Meier method and proportional hazards models.
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From the date of study enrollment to the first observation of progressive disease, assessed up to 5 years
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival (OS) for SNP ATIC/AICART - s10932606 Genotypes
Time Frame: From the date of study enrollment up to 5 years
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Kaplan-Meier estimates of median survival time for each genotype
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From the date of study enrollment up to 5 years
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MicroRNA Expression - miR-215-5p
Time Frame: Baseline
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Mean microRNAs expression of mi-215-5p in tumor tissues of responders and non-responders using a microfabricated device called a gene chip.
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Baseline
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Nikhil Khushalani, Roswell Park Cancer Institute
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Disease Attributes
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Stomach Diseases
- Head and Neck Neoplasms
- Esophageal Diseases
- Neoplasms, Squamous Cell
- Stomach Neoplasms
- Carcinoma
- Recurrence
- Adenocarcinoma
- Carcinoma, Squamous Cell
- Esophageal Neoplasms
- Esophageal Squamous Cell Carcinoma
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Folic Acid Antagonists
- Oxaliplatin
- 10-deazaaminopterin
Other Study ID Numbers
- I 169210 (Other Identifier: Roswell Park Cancer Institute)
- P30CA016056 (U.S. NIH Grant/Contract)
- NCI-2010-01583 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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