CHFR Methylation Status Esophageal Cancer Study

NCT01372202 | Terminated Phase 2 Results DMC

• 3 other identifiers: J10130NA_00042668R33CA127055
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Esophageal Cancer

Keywords

Operable; Based on CHFR Methylation Status; Diagnostic Biopsies

Outcome Measures

Primary Outcomes (1)

• Pathological Complete Response

  CHFR methylation status correlates with response to taxane containing platinum-based combination therapy and tumor response involving operable Esophageal Cancer. Perform analysis comparing detection of CHFR in tumor and plasma.

  3 years

Secondary Outcomes (3)

• Survival

  3 years

• Time to Disease Progression

  3 years

• Esophageal Tumor CHFR Methylation and Detection in Plasma

  3 years

Study Arms (3)

Arm A

ACTIVE COMPARATOR

Paclitaxel with Cisplatin along with Radiotherapy and followed by Esophagectomy

Drug: Paclitaxel; Drug: Cisplatin; Radiation: Radiotherapy; Procedure: Esophagectomy

Arm B

ACTIVE COMPARATOR

Cisplatin or Oxaliplatin with 5-Fluorouracil along with Radiotherapy and followed by Esophagectomy

Drug: Cisplatin; Drug: Oxaliplatin; Drug: 5-Fluorouracil; Radiation: Radiotherapy; Procedure: Esophagectomy

Arm C

ACTIVE COMPARATOR

Cisplatin with 5-Fluorouracil along with Radiotherapy and followed by Esophagectomy

Drug: Cisplatin; Drug: 5-Fluorouracil; Radiation: Radiotherapy; Procedure: Esophagectomy

Interventions

Paclitaxel DRUG

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

Also known as: Abraxane, Taxol

Arm A

Cisplatin DRUG

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.

Also known as: Platinol

Arm A; Arm B; Arm C

Oxaliplatin DRUG

Oxaliplatin 85 mg/m2 days 1, 15, 29.

Also known as: Eloxatin

Arm B

5-Fluorouracil DRUG

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.

Also known as: 5-FU, Adrucil, Carac, Efudex, Fluorouracil

Arm B; Arm C

Radiotherapy RADIATION

Patients will be treated 5 days/week at 1.8 Gy/day to a total dose of 45Gy.

Also known as: IMRT

Arm A; Arm B; Arm C

Esophagectomy PROCEDURE

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).

Also known as: Resection

Arm A; Arm B; Arm C

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed adenocarcinoma of the esophagus or GE junction
• Patient must be untreated with chemotherapy, radiation therapy, or surgery for this diagnosis of esophageal cancer. (Endoscopy with biopsy and dilation is permitted.)
• 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.
• 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).
• Patients must have had an endoscopic ultrasound
• Patients must have had a staging PET scan
• Age ≥ 18 and ≤ 75
• ECOG performance status 0-1.
• Surgically resectable tumor
• Patients with a history of a curatively treated malignancy must be disease-free and have a survival prognosis that exceeds three years.
• 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

You may not qualify if:

• Patients may not be receiving any investigational agents.
• Incomplete healing from previous major surgery.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to agents they are assigned to.
• 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.
• 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.
• 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.
• Patients from whom biopsy tissue cannot be obtained for correlate study analysis.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Ronan Kelly, M.D.

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

Paclitaxel; Albumin-Bound Paclitaxel; Cisplatin; Oxaliplatin; Fluorouracil; Radiotherapy; Esophagectomy

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics; Digestive System Surgical Procedures; Surgical Procedures, Operative

Results Point of Contact

• Title: Ronan Kelly, MD
• Organization: SKCCC

rkelly25@jhmi.edu

443-287-0005

Study Officials

• Ronan Kelly, M.D.

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2011
• First Posted: June 13, 2011
• Study Start: June 1, 2011
• Primary Completion: June 1, 2014
• Study Completion: October 1, 2014
• Last Updated: January 25, 2019
• Results First Posted: August 30, 2017

Record last verified: 2019-01

Locations

US (1)