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

NCT01178944 | Completed Phase 2 Results DMC

• 3 other identifiers: I 169210NCI-2010-01583P30CA016056
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  Overall response rate to combination pralatrexate and oxaliplatin as assessed by Response Evaluation Criteria in Solid Tumors version 1.1. Objective responses will be confirmed 4 weeks after first documentation of response. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

  Up to 5 years

Secondary Outcomes (3)

• Number of Participants With an Adverse Event

  Up to 30 days after the last dose of study drug(s)

• Overall Survival (OS)

  From the date of study enrollment to the time of death from any cause, assessed up to 5 years

• Time to Progression (TTP)

  From the date of study enrollment to the first observation of progressive disease, assessed up to 5 years

Other Outcomes (2)

• Overall Survival (OS) for SNP ATIC/AICART - s10932606 Genotypes

  From the date of study enrollment up to 5 years

• MicroRNA Expression - miR-215-5p

  Baseline

Study Arms (1)

Treatment (pralatrexate, oxaliplatin)

EXPERIMENTAL

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; Drug: Oxaliplatin; Drug: Pralatrexate

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (pralatrexate, oxaliplatin)

Oxaliplatin DRUG

Given IV

Also known as: 1-OHP, Dacotin, Dacplat, Diaminocyclohexane Oxalatoplatinum, Eloxatin, Eloxatine, JM-83, Oxalatoplatin, Oxalatoplatinum, RP 54780, RP-54780, SR-96669

Treatment (pralatrexate, oxaliplatin)

Pralatrexate DRUG

Given IV

Also known as: 10-propargyl-10-deazaaminopterin, Folotyn, PDX

Treatment (pralatrexate, oxaliplatin)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead
• National Cancer Institute (NCI): collaborator
• National Comprehensive Cancer Network: collaborator

Study Sites (2)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Rochester General Hospital

Rochester, New York, 14621, United States

Location

MeSH Terms

Conditions

Adenocarcinoma Of Esophagus; Esophageal Squamous Cell Carcinoma; Stomach Neoplasms

Interventions

Oxaliplatin; 10-propargyl-10-deazaaminopterin

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals

Results Point of Contact

• Title: Senior Administrator, Compliance - Clinical Research Services
• Organization: Roswell Park Cancer Institute

716-845-2300

Study Officials

• Nikhil Khushalani

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2010
• First Posted: August 10, 2010
• Study Start: September 1, 2010
• Primary Completion: January 1, 2015
• Study Completion: November 1, 2015
• Last Updated: December 13, 2017
• Results First Posted: December 13, 2017

Record last verified: 2017-11

Locations

US (2)