Combination Chemotherapy in Treating Patients With Previously Untreated Stage II or Stage III Esophageal Cancer That Can Be Removed By Surgery

Esophageal Cancer Clinical Trial

Official title:

A Nonrandomized Phase II Study: Feasibility and Outcome of Neo Adjuvant Chemotherapy With Oxaliplatin, Fluorodeoxyuridine (FUdR), Taxotere and Leucovorin in the Treatment of Previously Untreated Advanced Esophago-Gastric Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00448760
• Other study ID #: UMIAMI-20040006
• Secondary ID: SCCC-2003151WIRB
• Status: Completed
• Phase: Phase 2
• First received: March 15, 2007
• Last updated: July 25, 2014
• Start date: October 2004
• Est. completion date: April 2010

Study information

• Verified date: August 2013
• Source: University of Miami Sylvester Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, floxuridine, docetaxel, and leucovorin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Giving chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This phase II trial is studying how well combination chemotherapy works in treating patients with previously untreated stage II or stage III esophageal cancer that can be removed by surgery.

Description:

OBJECTIVES:

Primary

• Determine whether neoadjuvant chemotherapy comprising oxaliplatin, floxuridine, docetaxel, and leucovorin calcium improves the rate of pathologic complete response in patients with previously untreated, resectable stage II or III adenocarcinoma of the esophagus.

Secondary

• Determine the progression-free and overall survival of patients treated with this regimen.

• Determine the clinical response rates (complete response and partial response) in patients treated with this regimen.

• Evaluate thymidylate synthase (TS), mRNA gene expression, TS activity, and TS and mRNA sequence, to determine the altered spots as related to drug resistance in these patients.

• Evaluate the potential for genome-wide gene expression profiling to predict response to therapy, recurrence, progression-free survival, overall survival, and drug sensitivity and resistance in these patients.

• Define the role of 5' untranslated region (5'-UTR) on translation and drug resistance in these patients.

• Evaluate, by bone marrow aspirate analysis and flow cytometry, the initial presence of cancer cells in the marrow, and clearance of these cells after treatment with this regimen.

• Evaluate the safety of this regimen in these patients.

• Assess quality of life of patients during and after treatment with this regimen.

OUTLINE: This is a nonrandomized, open-label study.

Patients receive oxaliplatin IV over 2 hours on days 1 and 15 and docetaxel IV over 30 minutes, floxuridine IV over 24 hours, and leucovorin calcium IV over 24 hours on days 1, 8, and 15. Treatment repeats every 4 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo surgery after completion of chemotherapy. Patients who achieve pathologic complete response (pCR) receive no further chemotherapy. Patients who have not achieved a pCR receive 2 courses of adjuvant chemotherapy (same regimen as the neoadjuvant chemotherapy) beginning 3 weeks after surgery.

Patients undergo blood and tissue collection periodically for correlative studies. Samples are analyzed for thymidylate synthase (TS), mRNA gene expression, TS activity, and TS and mRNA sequence by bone marrow aspirate, flow cytometry, and quantitative reverse transcriptase-polymerase chain reaction.

Quality of life will be assessed at baseline, after neoadjuvant chemotherapy, after adjuvant therapy, and at the first 3-month follow-up visit.

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 34 patients will be accrued for this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: April 2010
• Est. primary completion date: April 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Diagnosis of adenocarcinoma of the esophagus meeting the following criteria:

• Stage II or III disease

• Resectable disease

• Previously untreated disease

• No stage I (mucosal only) or stage IV (metastatic) disease

PATIENT CHARACTERISTICS:

• WBC > 3,000/mm^3

• Absolute neutrophil count > 1,500/mm^3

• Platelet count > 100,000/mm^3

• Creatinine = 2.0 mg/dL

• Bilirubin < 2 times normal

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• Must have central venous access

• No other malignancy within the past 5 years

• No concurrent medical or psychiatric problem that would preclude study treatment

• No contraindications to paclitaxel

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy or radiotherapy to the esophagus

• No oral cryotherapy (e.g., ice chips) on day 1 of each course

Study Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Esophageal Cancer
• Esophageal Neoplasms

Intervention

Drug:
• Docetaxel
Intravenously, 25 mg/m2, over 30 minutes, 2 cycles
• Floxuridine
Intravenuosly, 110mg/kg, continuous infusion over 24 hours, 2 cycles
• Leucovorin
Intravenuosly, 500mg/m2, continuous infusion over 24 hours, 2 cycles
• Oxaliplatin
Intravenously, 85 mg/m2, over 2 hours, 2 cycles

Genetic:
• Microarray analysis
Analysis of tumor for pathologic response to protocol therapy
• reverse transcriptase-polymerase chain reaction
Analysis of tumor for pathologic response to protocol therapy

Procedure:
• Conventional surgery
Surgical removal of tumor for correlative studies

Locations

Country	Name	City	State
United States	University of Miami Sylvester Comprehensive Cancer Center - Miami	Miami	Florida

Sponsors (1)

Lead Sponsor	Collaborator
University of Miami Sylvester Comprehensive Cancer Center

Country where clinical trial is conducted

United States, 

References & Publications (1)

Solomon N, Mezentsev D, Reis I, Lima M, Rios J, Avisar E, Franceschi D, Livingstone A, Podolsky L, Ardalan B. A phase II study of neoadjuvant and adjuvant chemotherapy with 5-fluorodeoxyuridine, leucovorin, oxaliplatin and docetaxel in the treatment of pr — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathologic Complete Response	No evidence of cellular residual cancerous cells as evidenced by tumor tissue samples taken via surgery at the end of neo-adjuvant chemotherapy.	8 - 16 weeks	No
Secondary	Clinical Response	Overall response = Complete response (CR) + Partial Response (PR). Evaluated via endoscopic ultrasounds, PET and CT scans of the chest: Complete Response (CR) applies to participants complete disappearance of all measurable and evaluable disease. No new lesion. No disease related symptoms. No evidence of non-evaluable disease, including tumor markers and other laboratory values.; Partial Response (PR) applies to participants with at least 50 percent reduction in the sum of the products of bi-dimensional perpendicular diameters of all measurable lesions. No progression of evaluable disease. No new lesions.	8 - 16 weeks	No
Secondary	Median Progression-free Survival (PFS)		24 months	No
Secondary	Overall Survival		24 months	No