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

This study is currently recruiting participants.
Verified October 2013 by Roswell Park Cancer Institute
Sponsor:
Collaborator:
National Comprehensive Cancer Network
Information provided by (Responsible Party):
Roswell Park Cancer Institute
ClinicalTrials.gov Identifier:
NCT01178944
First received: August 9, 2010
Last updated: October 28, 2013
Last verified: October 2013

August 9, 2010
October 28, 2013
September 2010
May 2014   (final data collection date for primary outcome measure)
Overall response rate to combination pralatrexate and oxaliplatin as assessed by RECIST [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01178944 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
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 Esophagogastric Cancer: A Phase II Trial With Predictive Molecular Correlates

RATIONALE: 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 or by stopping them from dividing. Giving pralatrexate and oxaliplatin together may kill more tumor cells. PURPOSE: This phase II trial is studying how well pralatrexate and oxaliplatin work in treating patients with unresectable or metastatic esophageal, stomach, or gastroesophageal junction cancer.

PRIMARY OBJECTIVES: I. To determine the overall response rate in patients with advanced esophago-gastric cancer 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 microRNA expression profiling of the epithelial component of the tumor. OUTLINE: Patients receive pralatrexate IV over 3-5 minutes and oxaliplatin IV over 2 hours on day 1. Treatment repeats every 2 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity. 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 Esophagus
  • Adenocarcinoma of the Gastroesophageal Junction
  • Diffuse Adenocarcinoma of the Stomach
  • Intestinal Adenocarcinoma of the Stomach
  • Mixed Adenocarcinoma of the Stomach
  • Recurrent Esophageal Cancer
  • Recurrent Gastric Cancer
  • Squamous Cell Carcinoma of the Esophagus
  • Stage III Esophageal Cancer
  • Stage III Gastric Cancer
  • Stage IV Esophageal Cancer
  • Stage IV Gastric Cancer
  • Drug: pralatrexate
    Given IV
    Other Names:
    • FOLOTYN
    • PDX
  • Drug: oxaliplatin
    Given IV
    Other Names:
    • 1-OHP
    • Dacotin
    • Dacplat
    • diaminocyclohexane oxalatoplatinum
    • Eloxatin
    • L-OHP
  • Other: pharmacogenomic studies
    Correlative studies
    Other Name: Pharmacogenomic Study
  • Genetic: RNA analysis
    Correlative studies
  • Genetic: polymorphism analysis
    Correlative studies
  • Genetic: polymerase chain reaction
    Correlative studies
    Other Name: PCR
  • Genetic: microarray analysis
    Correlative studies
    Other Name: gene expression profiling
  • Procedure: esophagogastroduodenoscopy
    Correlative studies
    Other Name: EGD
  • Procedure: biopsy
    Correlative studies
    Other Name: biopsies
  • Other: laboratory biomarker analysis
    Correlative studies
Experimental: Arm I
Patients receive pralatrexate IV over 3-5 minutes and oxaliplatin IV over 2 hours on day 1. Treatment repeats every 2 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Interventions:
  • Drug: pralatrexate
  • Drug: oxaliplatin
  • Other: pharmacogenomic studies
  • Genetic: RNA analysis
  • Genetic: polymorphism analysis
  • Genetic: polymerase chain reaction
  • Genetic: microarray analysis
  • Procedure: esophagogastroduodenoscopy
  • Procedure: biopsy
  • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
33
Not Provided
May 2014   (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 included 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
  • 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
  • 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
  • Nursing women are ineligible
Both
18 Years and older
No
Contact: AskRPCI 877-275-7724 AskRPCI@RoswellPark.org
United States
 
NCT01178944
I 169210, NCI-2010-01583
No
Roswell Park Cancer Institute
Roswell Park Cancer Institute
National Comprehensive Cancer Network
Principal Investigator: Nikhil Khushalani Roswell Park Cancer Institute
Roswell Park Cancer Institute
October 2013

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