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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

Phase 2
18 Years
Open (Enrolling)
Esophageal Cancer

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Trial Information

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

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.

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, percardium 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-fluorouricil 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, celocoxib,
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.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Esophageal Tumor Response

Outcome Description:

CHFR methylation status correlates with response to taxane containing platinum-based combination therapy and tumor response involving operable Esophageal Cancer.

Outcome Time Frame:

3 years

Safety Issue:



United States: Food and Drug Administration

Study ID:




Start Date:

June 2011

Completion Date:

June 2014

Related Keywords:

  • Esophageal Cancer
  • Operable
  • Based on CHFR Methylation Status
  • Diagnostic Biopsies
  • Esophageal Diseases
  • Esophageal Neoplasms



Ronan Kelly, MD,Baltimore, Maryland  21231