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

Primary Purpose

Adenocarcinoma of the Gastroesophageal Junction, Esophageal Undifferentiated Carcinoma, Gastric Adenocarcinoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Laboratory Biomarker Analysis
Oxaliplatin
Pralatrexate
Sponsored by
Roswell Park Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adenocarcinoma of the Gastroesophageal Junction

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Roswell Park Cancer Institute
  • Rochester General Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (pralatrexate, oxaliplatin)

Arm Description

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.

Outcomes

Primary Outcome Measures

Overall Response Rate
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

Number of Participants With an Adverse Event
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
Overall Survival (OS)
Estimated using the Kaplan-Meier method and proportional hazards models.
Time to Progression (TTP)
Estimated using the Kaplan-Meier method and proportional hazards models.

Full Information

First Posted
August 9, 2010
Last Updated
November 14, 2017
Sponsor
Roswell Park Cancer Institute
Collaborators
National Cancer Institute (NCI), National Comprehensive Cancer Network
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1. Study Identification

Unique Protocol Identification Number
NCT01178944
Brief Title
Pralatrexate and Oxaliplatin in Treating Patients With Unresectable or Metastatic Esophageal, Stomach, or Gastroesophageal Junction Cancer
Official Title
Pralatrexate in Combination With Oxaliplatin in Advanced Esophago-gastric Cancer: A Phase II Trial With Predictive Molecular Correlates
Study Type
Interventional

2. Study Status

Record Verification Date
November 2017
Overall Recruitment Status
Completed
Study Start Date
September 2010 (undefined)
Primary Completion Date
January 2015 (Actual)
Study Completion Date
November 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Roswell Park Cancer Institute
Collaborators
National Cancer Institute (NCI), National Comprehensive Cancer Network

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
35 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (pralatrexate, oxaliplatin)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Other Intervention Name(s)
1-OHP, Dacotin, Dacplat, Diaminocyclohexane Oxalatoplatinum, Eloxatin, Eloxatine, JM-83, Oxalatoplatin, Oxalatoplatinum, RP 54780, RP-54780, SR-96669
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Pralatrexate
Other Intervention Name(s)
10-propargyl-10-deazaaminopterin, Folotyn, PDX
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Overall Response Rate
Description
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.
Time Frame
Up to 5 years
Secondary Outcome Measure Information:
Title
Number of Participants With an Adverse Event
Description
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
Time Frame
Up to 30 days after the last dose of study drug(s)
Title
Overall Survival (OS)
Description
Estimated using the Kaplan-Meier method and proportional hazards models.
Time Frame
From the date of study enrollment to the time of death from any cause, assessed up to 5 years
Title
Time to Progression (TTP)
Description
Estimated using the Kaplan-Meier method and proportional hazards models.
Time Frame
From the date of study enrollment to the first observation of progressive disease, assessed up to 5 years
Other Pre-specified Outcome Measures:
Title
Overall Survival (OS) for SNP ATIC/AICART - s10932606 Genotypes
Description
Kaplan-Meier estimates of median survival time for each genotype
Time Frame
From the date of study enrollment up to 5 years
Title
MicroRNA Expression - miR-215-5p
Description
Mean microRNAs expression of mi-215-5p in tumor tissues of responders and non-responders using a microfabricated device called a gene chip.
Time Frame
Baseline

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nikhil Khushalani
Organizational Affiliation
Roswell Park Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Name
Rochester General Hospital
City
Rochester
State/Province
New York
ZIP/Postal Code
14621
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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