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:
Collaborator:
Information provided by (Responsible Party):
Roswell Park Cancer Institute
ClinicalTrials.gov Identifier:
NCT01178944
First received: August 9, 2010
Last updated: June 30, 2015
Last verified: June 2015

August 9, 2010
June 30, 2015
September 2010
January 2015   (final data collection date for primary outcome measure)
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.
Overall response rate to combination pralatrexate and oxaliplatin as assessed by RECIST [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01178944 on ClinicalTrials.gov Archive Site
  • 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.
  • Toxicity as assessed by NCI CTCAE version 4.0 [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
  • Time to progression [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To examine whether functionally relevant polymorphisms of genes of the folate metabolism pathway correlate with efficacy and toxicity of pralatrexate. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • To examine whether response to pralatrexate can be predicted by microRNA expression profiling of the epithelial component of the tumor. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • 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.
Not Provided
 
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

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.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • 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
    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
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.
Interventions:
  • Other: Laboratory Biomarker Analysis
  • Drug: Oxaliplatin
  • Drug: Pralatrexate
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
35
Not Provided
January 2015   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01178944
I 169210, NCI-2010-01583, I 169210, P30CA016056
Not Provided
Roswell Park Cancer Institute
Roswell Park Cancer Institute
National Cancer Institute (NCI)
Principal Investigator: Nikhil Khushalani Roswell Park Cancer Institute
Roswell Park Cancer Institute
June 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP