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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
National Comprehensive Cancer Network
Information provided by (Responsible Party):
Roswell Park Cancer Institute
ClinicalTrials.gov Identifier:
NCT01178944
First received: August 9, 2010
Last updated: August 27, 2015
Last verified: August 2015
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Roswell Park Cancer Institute:

Primary Outcome Measures:
  • Overall response rate to combination pralatrexate and oxaliplatin as assessed by Response Evaluation Criteria in Solid Tumors version 1.1 [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Objective responses will be confirmed 4 weeks after first documentation of response.


Secondary Outcome Measures:
  • 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) ] [ Designated as safety issue: Yes ]
  • Overall survival (OS) [ Time Frame: From the date of study enrollment to the time of death from any cause, assessed up to 5 years ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier method and proportional hazards models. Continuous variables will be summarized with commonly used statistics (mean, standard deviation, median, etc.), with sub-group associations tested using the Wilcoxon rank sum test. Categorical variables will be summarized in contingency tables, with associations of interest assessed using Fisher's exact test.

  • Time to progression (TTP) [ Time Frame: From the date of study enrollment to the first observation of progressive disease, assessed up to 5 years ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier method and proportional hazards models. Continuous variables will be summarized with commonly used statistics (mean, standard deviation, median, etc.), with sub-group associations tested using the Wilcoxon rank sum test. Categorical variables will be summarized in contingency tables, with associations of interest assessed using Fisher's exact test.


Other Outcome Measures:
  • Dichotomous genomic events (i.e., homozygote/heterozygote, or presence/absence of polymorphisms, etc.) [ Time Frame: Baseline or any time during study ] [ Designated as safety issue: No ]
    Correlations of the haplotype-tagged single nucleotide polymorphism (SNPs) with response, OS, and TTP will be explored by multivariate logistic and Cox proportional hazards models, to explore the impact of these germline SNPs on binary and time to event outcomes. These exploratory comparisons will be carried out on the entire cohort, as well as within different patient subgroups such as responders, and progression-free and stable patients if feasible.

  • MicroRNA expression profiles [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Initial studies will be conducted to test and optimize individual miRNAs for maximum sensitivity and specificity to predict chemosensitivity, inferring differences in the distributions of biomarkers with stringent statistical multiple testing error control procedures. A 2-sample two-ways test of mean differences in mir log expression by discrete treatment outcome (toxicity or efficacy) will be performed, with a Wilcoxon rank sum test.


Enrollment: 35
Study Start Date: September 2010
Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
  • OXALIPLATIN
  • RP 54780
  • RP-54780
  • SR-96669
Drug: Pralatrexate
Given IV
Other Names:
  • 10-propargyl-10-deazaaminopterin
  • Folotyn
  • PDX
  • PRALATREXATE

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01178944

Locations
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 Comprehensive Cancer Network
Investigators
Principal Investigator: Nikhil Khushalani Roswell Park Cancer Institute
  More Information

No publications provided

Responsible Party: Roswell Park Cancer Institute
ClinicalTrials.gov Identifier: NCT01178944     History of Changes
Other Study ID Numbers: I 169210, NCI-2010-01583, I 169210, P30CA016056
Study First Received: August 9, 2010
Last Updated: August 27, 2015
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma
Carcinoma, Squamous Cell
Esophageal Neoplasms
Stomach Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Esophageal Diseases
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Head and Neck Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Neoplasms, Squamous Cell
Stomach Diseases
10-deazaaminopterin
Aminopterin
Oxaliplatin
Antineoplastic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on August 27, 2015