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:
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 6, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
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
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
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 Esophagogastric 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 RECIST [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 33
Study Start Date: September 2010
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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

Detailed Description:

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.

  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 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
  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
Study First Received: August 9, 2010
Last Updated: August 6, 2014
Health Authority: United States: Institutional Review Board

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

ClinicalTrials.gov processed this record on August 20, 2014