Clinical trial NCT00448760: Combination Chemotherapy in Treating Patients With Previously Untreated Stage II or Stage III Esophageal Cancer That Can Be Removed By Surgery
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Esophageal Cancer
Keywords: stage II esophageal cancer
stage III esophageal cancer
adenocarcinoma of the esophagus
Lead sponsor: University of Miami
Sponsor class: OTHER
First posted: 2007-03-19
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Pathologic Complete Response
timeFrame: 8 - 16 weeks
Secondary outcomes:
measure: Clinical Response
timeFrame: 8 - 16 weeks
measure: Median Progression-free Survival (PFS)
timeFrame: 24 months
measure: Overall Survival
timeFrame: 24 months
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami Sylvester Comprehensive Cancer Center - Miami
state: Florida
Study officials:
affiliation: University of Miami Sylvester Comprehensive Cancer Center
name: Bach Ardalan, MD
role: STUDY_CHAIR
References:
citation: 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.