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

NCT ID: NCT00448760

Last Updated: 2017-02-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-10-31
• Study Completion Date: 2010-04-30

Brief 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.

Detailed 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.

Conditions

Esophageal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Neoadjuvant + Adjuvant Chemotherapy

Group Type: EXPERIMENTAL

Docetaxel

Intervention Type: DRUG

Intravenously, 25 mg/m2, over 30 minutes, 2 cycles

Floxuridine

Intervention Type: DRUG

Intravenuosly, 110mg/kg, continuous infusion over 24 hours, 2 cycles

Leucovorin

Intervention Type: DRUG

Intravenuosly, 500mg/m2, continuous infusion over 24 hours, 2 cycles

Oxaliplatin

Intervention Type: DRUG

Intravenously, 85 mg/m2, over 2 hours, 2 cycles

Microarray analysis

Intervention Type: GENETIC

Analysis of tumor for pathologic response to protocol therapy

reverse transcriptase-polymerase chain reaction

Intervention Type: GENETIC

Analysis of tumor for pathologic response to protocol therapy

Conventional surgery

Intervention Type: PROCEDURE

Surgical removal of tumor for correlative studies

Interventions

Docetaxel

Intravenously, 25 mg/m2, over 30 minutes, 2 cycles

Intervention Type: DRUG

Floxuridine

Intravenuosly, 110mg/kg, continuous infusion over 24 hours, 2 cycles

Intervention Type: DRUG

Leucovorin

Intravenuosly, 500mg/m2, continuous infusion over 24 hours, 2 cycles

Intervention Type: DRUG

Oxaliplatin

Intravenously, 85 mg/m2, over 2 hours, 2 cycles

Intervention Type: DRUG

Microarray analysis

Analysis of tumor for pathologic response to protocol therapy

Intervention Type: GENETIC

reverse transcriptase-polymerase chain reaction

Analysis of tumor for pathologic response to protocol therapy

Intervention Type: GENETIC

Conventional surgery

Surgical removal of tumor for correlative studies

Intervention Type: PROCEDURE

Other Intervention Names

Taxotere; FUdR

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Miami

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bach Ardalan, MD

Role: STUDY_CHAIR

University of Miami Sylvester Comprehensive Cancer Center

Locations

University of Miami Sylvester Comprehensive Cancer Center - Miami

Miami, Florida, United States

Countries

United States

References

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 previously untreated advanced esophageal adenocarcinoma. Jpn J Clin Oncol. 2011 Apr;41(4):469-76. doi: 10.1093/jjco/hyq239. Epub 2011 Jan 21.

Reference Type: RESULT

PMID: 21258083 (View on PubMed)

Other Identifiers

SCCC-2003151

Identifier Type: OTHER

Identifier Source: secondary_id

WIRB-20051464

Identifier Type: OTHER

Identifier Source: secondary_id

20040006

Identifier Type: -

Identifier Source: org_study_id