CHFR Methylation Status Esophageal Cancer Study

Phase 2

Terminated

• Conditions: Esophageal Cancer
• Interventions: Drug: Paclitaxel; Drug: Cisplatin; Drug: Oxaliplatin; Radiation: Radiotherapy; Drug: 5-Fluorouracil; Procedure: Esophagectomy

• Registration Number: NCT01372202
• Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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.

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2011-06
• Study First Submitted: 2011-06-09
• Study First Submitted QC: 2011-06-10
• Study First Posted: 2011-06-13
• Primary Completion: 2014-06
• Study Completion: 2014-10-01
• Results First Submitted: 2017-05-11
• Results First Submitted QC: 2017-07-28
• Results First Posted: 2017-08-30
• Status Verified: 2019-01
• Last Update Submitted: 2019-01-23
• Last Update Posted: 2019-01-25

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 31

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A	Radiotherapy	Paclitaxel with Cisplatin along with Radiotherapy and followed by Esophagectomy
Arm B	Radiotherapy	Cisplatin or Oxaliplatin with 5-Fluorouracil along with Radiotherapy and followed by Esophagectomy
Arm C	Esophagectomy	Cisplatin with 5-Fluorouracil along with Radiotherapy and followed by Esophagectomy
Arm A	Esophagectomy	Paclitaxel with Cisplatin along with Radiotherapy and followed by Esophagectomy
Arm C	Radiotherapy	Cisplatin with 5-Fluorouracil along with Radiotherapy and followed by Esophagectomy
Arm B	Esophagectomy	Cisplatin or Oxaliplatin with 5-Fluorouracil along with Radiotherapy and followed by Esophagectomy
Arm A	Paclitaxel	Paclitaxel with Cisplatin along with Radiotherapy and followed by Esophagectomy
Arm A	Cisplatin	Paclitaxel with Cisplatin along with Radiotherapy and followed by Esophagectomy
Arm B	Cisplatin	Cisplatin or Oxaliplatin with 5-Fluorouracil along with Radiotherapy and followed by Esophagectomy
Arm B	Oxaliplatin	Cisplatin or Oxaliplatin with 5-Fluorouracil along with Radiotherapy and followed by Esophagectomy
Arm B	5-Fluorouracil	Cisplatin or Oxaliplatin with 5-Fluorouracil along with Radiotherapy and followed by Esophagectomy
Arm C	5-Fluorouracil	Cisplatin with 5-Fluorouracil along with Radiotherapy and followed by Esophagectomy
Arm C	Cisplatin	Cisplatin with 5-Fluorouracil along with Radiotherapy and followed by Esophagectomy

Primary Outcome Measures

Name	Time	Method
Pathological Complete Response	3 years	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.

Secondary Outcome Measures

Name	Time	Method
Survival	3 years	Overall survival with given treatment strategy.
Time to Disease Progression	3 years	To determine time to disease progression with this treatment strategy.
Esophageal Tumor CHFR Methylation and Detection in Plasma	3 years	To determine the agreement between tumor CHFR methylation and detection in plasma.

Trial Locations

Locations (1)

Ronan Kelly, M.D.; 🇺🇸 Baltimore, Maryland, United States