CHFR Methylation Status Esophageal Cancer Study

NCT ID: NCT01372202

Last Updated: 2019-01-25

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-06-30
• Study Completion Date: 2014-10-01

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.

Conditions

Esophageal Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A

Paclitaxel with Cisplatin along with Radiotherapy and followed by Esophagectomy

Group Type: ACTIVE_COMPARATOR

Paclitaxel

Intervention Type: DRUG

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

Cisplatin

Intervention Type: 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.

Radiotherapy

Intervention Type: RADIATION

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

Esophagectomy

Intervention Type: 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).

Arm B

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

Group Type: ACTIVE_COMPARATOR

Cisplatin

Intervention Type: 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.

Oxaliplatin

Intervention Type: DRUG

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

5-Fluorouracil

Intervention Type: 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.

Radiotherapy

Intervention Type: RADIATION

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

Esophagectomy

Intervention Type: 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).

Arm C

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

Group Type: ACTIVE_COMPARATOR

Cisplatin

Intervention Type: 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.

5-Fluorouracil

Intervention Type: 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.

Radiotherapy

Intervention Type: RADIATION

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

Esophagectomy

Intervention Type: 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).

Interventions

Paclitaxel

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

Intervention Type: 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.

Intervention Type: DRUG

Oxaliplatin

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

Intervention Type: 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.

Intervention Type: DRUG

Radiotherapy

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

Intervention Type: RADIATION

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).

Intervention Type: PROCEDURE

Other Intervention Names

Abraxane; Taxol; Platinol; Eloxatin; 5-FU; Adrucil; Carac; Efudex; Fluorouracil; IMRT; Resection

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ronan Kelly, M.D.

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

Ronan Kelly, M.D.

Baltimore, Maryland, United States

Countries

United States

Other Identifiers

NA_00042668

Identifier Type: OTHER

Identifier Source: secondary_id

R33CA127055

Identifier Type: NIH

Identifier Source: secondary_id

View Link

J10130

Identifier Type: -

Identifier Source: org_study_id