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

Sponsor:	Roswell Park Cancer Institute
Collaborator:	National Comprehensive Cancer Network
Information provided by (Responsible Party):	Roswell Park Cancer Institute
ClinicalTrials.gov Identifier:	NCT01178944

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:

MedlinePlus related topics: Cancer Esophageal Cancer Esophagus Disorders Stomach Cancer

Drug Information available for: Oxaliplatin Ribonucleic acid Pralatrexate

U.S. FDA Resources

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:	May 2013 (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

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

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

Contacts

Contact: AskRPCI

877-275-7724

AskRPCI@RoswellPark.org

Locations

United States, New York
Roswell Park Cancer Institute	Recruiting
Buffalo, New York, United States, 14263
Contact: Nikhil I. Khushalani 716-845-3099 nikhil.khushalani@roswellpark.org
Principal Investigator: Nikhil I. Khushalani

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:	January 11, 2012
Health Authority:	United States: Institutional Review Board

Additional relevant MeSH terms:

Adenocarcinoma
Carcinoma
Carcinoma, Squamous Cell
Esophageal Diseases
Esophageal Neoplasms
Stomach Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Gastrointestinal Diseases
Digestive System Diseases
Gastrointestinal Neoplasms

Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
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 May 24, 2012