CHFR Methylation Status Esophageal Cancer Study (J10130)

This study is currently recruiting participants.
Verified November 2013 by Sidney Kimmel Comprehensive Cancer Center
Sponsor:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01372202
First received: June 9, 2011
Last updated: November 7, 2013
Last verified: November 2013
  Purpose

This is a Phase 2 Study of Paclitaxel with Cisplatin versus Fluoropyrimidine with a Platinum Agent for Neoadjuvant Therapy in Operable Esophageal Cancer Based on CHFR Methylation Status in Diagnostic Biopsies.


Condition Intervention Phase
Esophageal Cancer
Drug: Paclitaxel with Cisplatin
Drug: Arm B
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Paclitaxel With Cisplatin Versus Fluoropyrimidine With a Platinum Agent for Neoadjuvant Therapy in Operable Esophageal Cancer Based on CHFR Methylation Status in Diagnostic Biopsies

Resource links provided by NLM:


Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • Esophageal Tumor Response [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    CHFR methylation status correlates with response to taxane containing platinum-based combination therapy and tumor response involving operable Esophageal Cancer.


Secondary Outcome Measures:
  • Survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    To determine the survival outcome with this treatment strategy.

  • Time to disease progression [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    To determine time to disease progression with this treatment strategy.

  • Esophageal tumor CHFR methylation and detection in plasma [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    To determine the agreement between tumor CHFR methylation and detection in plasma.


Estimated Enrollment: 56
Study Start Date: June 2011
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm A
Paclitaxel with Cisplatin
Drug: Paclitaxel with Cisplatin
Arm A
Active Comparator: Arm B
Fluoropyrimidine with a Platinum Agent for Neoadjuvant Therapy
Drug: Arm B
Fluoropyrimidine with a Platinum Agent for Neoadjuvant Therapy

Detailed Description:

Primary Objectives

• To determine the rate of pathological complete response when the inclusion of paclitaxel in neoadjuvant therapy is based on the presence or absence of CHFR methylation in diagnostic biopsy specimens.

Secondary Objectives

  • To determine the survival outcome with this treatment strategy.
  • To determine time to disease progression with this treatment strategy.
  • To determine the agreement between tumor CHFR methylation and detection in plasma.
  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically confirmed adenocarcinoma of the esophagus or GE junction
  2. Patient must be untreated with chemotherapy, radiation therapy, or surgery for this diagnosis of esophageal cancer. (Endoscopy with biopsy and dilation is permitted.)
  3. Tumor must be located between 20 cm from the teeth endoscopically and 2 cm into the gastric cardia. Cervical esophageal cancers and true gastric cancers are excluded.
  4. Stage T2-3/N0-3/M0 as determined by imaging studies and biopsy where appropriate. T4 disease is permitted if defined as resectable by the thoracic surgeon (involvement of the pleura, percardium or diaphragm).
  5. Patients must have had an endoscopic ultrasound
  6. Patients must have had a staging PET scan
  7. Age ≥ 18 and ≤ 75
  8. ECOG performance status 0-1.
  9. Surgically resectable tumor
  10. Patients with a history of a curatively treated malignancy must be disease-free and have a survival prognosis that exceeds three years.
  11. Patients must have adequate organ and marrow function as defined below:

    • absolute neutrophil count ≥ 1,000/mcL
    • platelets ≥ 100,000/mcL
    • total bilirubin ≤ 2 mg/dL
    • AST(SGOT)/ALT(SGPT) ≤ 2.5 X institutional ULN
    • creatinine < 1.5 X institutional ULN
  12. Female patients must not be pregnant or breast feeding. Radiotherapy is associated with significant birth defects and/or non-viable fetus. Paclitaxel, cisplatin, oxaliplatin, and 5-fluorouricil have teratogenic potential. A negative pregnancy test is required within 14 days of treatment for all women of childbearing potential. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, the patient should inform the treating physician immediately.
  13. Patients must have the ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  1. Patients may not be receiving any investigational agents.
  2. Incomplete healing from previous major surgery.
  3. History of allergic reactions attributed to compounds of similar chemical or biologic composition to agents they are assigned to.
  4. Concomitant use of phenytoin, carbamazepine, barbiturates, rifampicin, phenobarbital, or St John's Wort; these drugs induce CYP3A and may decrease levels paclitaxel. 5-FU is a strong CYP2C9 inducer, and concomitant use with carvedilol, celocoxib, fosphenytoin, fluoxetine, phenytoin, warfarin and other CYP2C9 substrates should be used with caution.
  5. Uncontrolled, inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  6. HIV-positive patients on combination antiretroviral therapy are ineligible because these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
  7. Patients from whom biopsy tissue cannot be obtained for correlate study analysis.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01372202

Locations
United States, Maryland
Ronan Kelly, MD, Recruiting
Baltimore, Maryland, United States, 21231
Contact: Ronan Kelly, MD,    443-287-0005    rkelly25@jhmi.edu   
Contact: Charles P Raines, CRNP, MSN    410-502-3696    craines1@jhmi.edu   
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01372202     History of Changes
Other Study ID Numbers: J10130, NA_00042668
Study First Received: June 9, 2011
Last Updated: November 7, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
Operable
Based on CHFR Methylation Status
Diagnostic Biopsies

Additional relevant MeSH terms:
Esophageal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Cisplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on April 17, 2014