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

• Sponsor: University of Miami (Other)
• Overall Status: Completed
• CT.gov ID: NCT00448760
• Collaborator: (none)
• Enrollment: 29
• Location: 1
• Arm: 1
• Duration (Months): 66
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Esophageal Cancer	Drug: Docetaxel; Drug: Floxuridine; Drug: Leucovorin; Drug: Oxaliplatin; Genetic: Microarray analysis; Genetic: reverse transcriptase-polymerase chain reaction; Procedure: Conventional surgery	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 29 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: Oct 1, 2004
• Actual Primary Completion Date: Apr 1, 2010
• Actual Study Completion Date: Apr 1, 2010

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Neoadjuvant + Adjuvant Chemotherapy

Drug: Docetaxel; Intravenously, 25 mg/m2, over 30 minutes, 2 cycles; Other Names: Taxotere ; Drug: Floxuridine; Intravenuosly, 110mg/kg, continuous infusion over 24 hours, 2 cycles; Other Names: FUdR ; Drug: Leucovorin; Intravenuosly, 500mg/m2, continuous infusion over 24 hours, 2 cycles; Drug: Oxaliplatin; Intravenously, 85 mg/m2, over 2 hours, 2 cycles; Genetic: Microarray analysis; Analysis of tumor for pathologic response to protocol therapy; Genetic: reverse transcriptase-polymerase chain reaction; Analysis of tumor for pathologic response to protocol therapy; Procedure: Conventional surgery; Surgical removal of tumor for correlative studies

Outcome Measures

Primary Outcome Measures

1. Pathologic Complete Response [8 - 16 weeks]

   No evidence of cellular residual cancerous cells as evidenced by tumor tissue samples taken via surgery at the end of neo-adjuvant chemotherapy.

Secondary Outcome Measures

1. Clinical Response [8 - 16 weeks]

   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.

2. Median Progression-free Survival (PFS) [24 months]

3. Overall Survival [24 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Miami Sylvester Comprehensive Cancer Center - Miami	Miami	Florida	United States	33136

Sponsors and Collaborators

• University of Miami

Investigators

• Study Chair: Bach Ardalan, MD, University of Miami Sylvester Comprehensive Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Miami
• ClinicalTrials.gov Identifier: NCT00448760
• Other Study ID Numbers: 20040006; SCCC-2003151; WIRB-20051464
• First Posted: Mar 19, 2007
• Last Update Posted: Feb 7, 2017
• Last Verified: Dec 1, 2016

• Keywords provided by University of Miami: stage II esophageal cancer; stage III esophageal cancer; adenocarcinoma of the esophagus
• Additional relevant MeSH terms: Esophageal Neoplasms; Leucovorin; Docetaxel; Oxaliplatin; Floxuridine

Study Results

Participant Flow

Arm/Group Title	Neoadjuvant + Adjuvant Chemotherapy
Arm/Group Description	Floxuridine : Intravenuosly, 110mg/kg, continuous infusion over 24 hours, 2 cycles Leucovorin : Intravenuosly, 500mg/m2, continuous infusion over 24 hours, 2 cycles Conventional surgery : Surgical removal of tumor for correlative studies reverse transcriptase-polymerase chain reaction : Analysis of tumor for pathologic response to protocol therapy Docetaxel : Intravenously, 25 mg/m2, over 30 minutes, 2 cycles Microarray analysis : Analysis of tumor for pathologic response to protocol therapy Oxaliplatin : Intravenously, 85 mg/m2, over 2 hours, 2 cycles
Period Title: Overall Study
STARTED	29
COMPLETED	26
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Single Arm
Arm/Group Description	5-Fluorodeoxyuridine, Leucovorin, Oxaliplatin and Docetaxel
Overall Participants	29
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	23 79.3%
>=65 years	6 20.7%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	62
Gender (Count of Participants)
Female	23 79.3%
Male	6 20.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	7 24.1%
Not Hispanic or Latino	22 75.9%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	3 10.3%
White	26 89.7%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	29 100%

Outcome Measures

1. Primary Outcome

Title	Pathologic Complete Response
Description	No evidence of cellular residual cancerous cells as evidenced by tumor tissue samples taken via surgery at the end of neo-adjuvant chemotherapy.
Time Frame	8 - 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Single Arm
Arm/Group Description	Floxuridine : Intravenuosly, 110mg/kg, continuous infusion over 24 hours, 2 cycles Leucovorin : Intravenuosly, 500mg/m2, continuous infusion over 24 hours, 2 cycles Conventional surgery : Surgical removal of tumor for correlative studies reverse transcriptase-polymerase chain reaction : Analysis of tumor for pathologic response to protocol therapy Docetaxel : Intravenously, 25 mg/m2, over 30 minutes, 2 cycles Microarray analysis : Analysis of tumor for pathologic response to protocol therapy Oxaliplatin : Intravenously, 85 mg/m2, over 2 hours, 2 cycles
Measure Participants	24
Number (90% Confidence Interval) [percentage of participants]	16.7 57.6%

2. Secondary Outcome

Title	Clinical Response
Description	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.
Time Frame	8 - 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Single Arm
Arm/Group Description	Floxuridine : Intravenuosly, 110mg/kg, continuous infusion over 24 hours, 2 cycles Leucovorin : Intravenuosly, 500mg/m2, continuous infusion over 24 hours, 2 cycles Conventional surgery : Surgical removal of tumor for correlative studies reverse transcriptase-polymerase chain reaction : Analysis of tumor for pathologic response to protocol therapy Docetaxel : Intravenously, 25 mg/m2, over 30 minutes, 2 cycles Microarray analysis : Analysis of tumor for pathologic response to protocol therapy Oxaliplatin : Intravenously, 85 mg/m2, over 2 hours, 2 cycles
Measure Participants	24
Number (90% Confidence Interval) [percentage of participants]	72.4 249.7%

3. Secondary Outcome

Title	Median Progression-free Survival (PFS)
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Single Arm
Arm/Group Description	Floxuridine : Intravenuosly, 110mg/kg, continuous infusion over 24 hours, 2 cycles Leucovorin : Intravenuosly, 500mg/m2, continuous infusion over 24 hours, 2 cycles Conventional surgery : Surgical removal of tumor for correlative studies reverse transcriptase-polymerase chain reaction : Analysis of tumor for pathologic response to protocol therapy Docetaxel : Intravenously, 25 mg/m2, over 30 minutes, 2 cycles Microarray analysis : Analysis of tumor for pathologic response to protocol therapy Oxaliplatin : Intravenously, 85 mg/m2, over 2 hours, 2 cycles
Measure Participants	26
Median (95% Confidence Interval) [months]	13.6

4. Secondary Outcome

Title	Overall Survival
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Single Arm
Arm/Group Description	Floxuridine : Intravenuosly, 110mg/kg, continuous infusion over 24 hours, 2 cycles Leucovorin : Intravenuosly, 500mg/m2, continuous infusion over 24 hours, 2 cycles Conventional surgery : Surgical removal of tumor for correlative studies reverse transcriptase-polymerase chain reaction : Analysis of tumor for pathologic response to protocol therapy Docetaxel : Intravenously, 25 mg/m2, over 30 minutes, 2 cycles Microarray analysis : Analysis of tumor for pathologic response to protocol therapy Oxaliplatin : Intravenously, 85 mg/m2, over 2 hours, 2 cycles
Measure Participants	29
Median (95% Confidence Interval) [months]	21.4

Adverse Events

Arm/Group Title	Single Arm
Arm/Group Description	Floxuridine : Intravenuosly, 110mg/kg, continuous infusion over 24 hours, 2 cycles Leucovorin : Intravenuosly, 500mg/m2, continuous infusion over 24 hours, 2 cycles Conventional surgery : Surgical removal of tumor for correlative studies reverse transcriptase-polymerase chain reaction : Analysis of tumor for pathologic response to protocol therapy Docetaxel : Intravenously, 25 mg/m2, over 30 minutes, 2 cycles Microarray analysis : Analysis of tumor for pathologic response to protocol therapy Oxaliplatin : Intravenously, 85 mg/m2, over 2 hours, 2 cycles
All Cause Mortality
	Single Arm
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Single Arm
	Affected / at Risk (%)	# Events
Total	25/29 (86.2%)
Blood and lymphatic system disorders
Grade 3 Neutropenia	8/29 (27.6%)
Grade 4 Neutropenia	3/29 (10.3%)
Grade 3 Febrile Neutropenia	3/29 (10.3%)
Grade 3Thrombocytopenia	1/29 (3.4%)
Gastrointestinal disorders
Grade 3 Diarrhea	5/29 (17.2%)
General disorders
Grade 3 Fatigue	9/29 (31%)
Grade 3 Deep Venous Thrombosis	1/29 (3.4%)
Grade 3 Nausea	1/29 (3.4%)
Other (Not Including Serious) Adverse Events
	Single Arm
	Affected / at Risk (%)	# Events
Total	0/29 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.