CHFR Methylation Status Esophageal Cancer Study (J10130)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 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: May 21, 2014
Last verified: May 2014
  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
Drug: Cisplatin
Drug: Oxaliplatin
Drug: 5-Fluorouracil
Radiation: Radiotherapy
Procedure: Esophagectomy
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 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm A
Paclitaxel with Cisplatin along with Radiotherapy and followed by Esophagectomy
Drug: Paclitaxel
Paclitaxel 50 mg/m² (1 hr) days 1, 8, 15, 22, 29.
Other Names:
  • Abraxane
  • Taxol
Drug: Cisplatin

Paclitaxel and cisplatin:

  • Paclitaxel 50 mg/m² (1 hr) days 1, 8, 15, 22, 29.
  • Cisplatin 30 mg/m² days 1, 8, 15, 22, 29.

Cisplatin and 5-fluorouracil:

  • 5-Fluorouracil 1000 mg/m2 per day over 24 hours days 1- 4 and 29 - 32.
  • Cisplatin 75 mg/m² days 1, 29.
Other Name: Platinol
Radiation: Radiotherapy
Patients will be treated 5 days/week at 1.8 Gy/day to a total dose of 45Gy.
Other Name: IMRT
Procedure: Esophagectomy
The type of resection (Ivor-Lewis, Transhiatal, etc.) will be left to the discretion of the operating surgeon. Resection will be completed between 5 and 8 weeks starting from the completion of chemotherapy and radiation (days 36 - 56).
Other Name: Resection
Active Comparator: Arm B
Cisplatin or Oxaliplatin with 5-Fluorouracil along with Radiotherapy and followed by Esophagectomy
Drug: Cisplatin

Paclitaxel and cisplatin:

  • Paclitaxel 50 mg/m² (1 hr) days 1, 8, 15, 22, 29.
  • Cisplatin 30 mg/m² days 1, 8, 15, 22, 29.

Cisplatin and 5-fluorouracil:

  • 5-Fluorouracil 1000 mg/m2 per day over 24 hours days 1- 4 and 29 - 32.
  • Cisplatin 75 mg/m² days 1, 29.
Other Name: Platinol
Drug: Oxaliplatin
Oxaliplatin 85 mg/m2 days 1, 15, 29.
Other Name: Eloxatin
Drug: 5-Fluorouracil

Oxaliplatin and 5-fluorouracil:

  • Oxaliplatin 85 mg/m2 days 1, 15, 29.
  • 5-Fluorouracil 180 mg/m2 prolonged infusion starting day 1 of radiation and completing on the final day of radiation (up to 40 days)

Cisplatin and 5-fluorouracil:

  • 5-Fluorouracil 1000 mg/m2 per day over 24 hours days 1-4 and 29-32.
  • Cisplatin 75 mg/m² days 1, 29.
Other Names:
  • 5-FU
  • Adrucil
  • Carac
  • Efudex
  • Fluorouracil
Radiation: Radiotherapy
Patients will be treated 5 days/week at 1.8 Gy/day to a total dose of 45Gy.
Other Name: IMRT
Procedure: Esophagectomy
The type of resection (Ivor-Lewis, Transhiatal, etc.) will be left to the discretion of the operating surgeon. Resection will be completed between 5 and 8 weeks starting from the completion of chemotherapy and radiation (days 36 - 56).
Other Name: Resection

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, pericardium 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-fluorouracil 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, celecoxib, 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
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: NCT01372202

Contacts
Contact: Ronan Kelly, M.D. 410-287-0005 rkelly25@jhmi.edu
Contact: Nancy Tsottles, RN 410-614-5483 tsottna@jhmi.edu

Locations
United States, Maryland
Ronan Kelly, M.D. Recruiting
Baltimore, Maryland, United States, 21287
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
Investigators
Principal Investigator: Ronan Kelly, M.D. Johns Hopkins University
  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: May 21, 2014
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
Oxaliplatin
Cisplatin
Fluorouracil
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators

ClinicalTrials.gov processed this record on September 14, 2014