Clinical trial NCT01372202: CHFR Methylation Status Esophageal Cancer Study
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Esophageal Cancer
Keywords: Operable
Based on CHFR Methylation Status
Diagnostic Biopsies
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2011-06-13
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Pathological Complete Response
timeFrame: 3 years
Secondary outcomes:
measure: Survival
timeFrame: 3 years
measure: Time to Disease Progression
timeFrame: 3 years
measure: Esophageal Tumor CHFR Methylation and Detection in Plasma
timeFrame: 3 years
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Ronan Kelly, M.D.
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Ronan Kelly, M.D.
role: PRINCIPAL_INVESTIGATOR
References: