Flavopiridol and Paclitaxel in Treating Patients With Locally Advanced or Metastatic Esophageal Cancer That Has Not Responded to Previous Paclitaxel

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00006245

Collaborator

National Cancer Institute (NCI) (NIH)

Location

Duration (Months)

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combining flavopiridol and paclitaxel in treating patients who have locally advanced or metastatic esophageal cancer that has not responded to previous paclitaxel therapy.

Condition or Disease	Intervention/Treatment	Phase
Esophageal Cancer	Drug: alvocidib Drug: paclitaxel	Phase 2

Detailed Description

OBJECTIVES:

Determine the response rate in patients with paclitaxel-refractory locally advanced or metastatic esophageal cancer treated with sequential paclitaxel and flavopiridol.
Determine the toxicity of this regimen in these patients.
Assess the quality of life of patients treated with this regimen.
Obtain pharmacokinetic information about this regimen.

OUTLINE: This is a multicenter study.

Patients receive paclitaxel IV over 3 hours on day 1 and flavopiridol IV continuously over 24 hours on day 2 weekly for 3 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, after courses 1 and 2, and then every 2 courses thereafter.

PROJECTED ACCRUAL: A total of 12-37 patients will be accrued for this study within 6-18 months.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

Phase II Trial of Flavopiridol and Paclitaxel in Patients With Paclitaxel-Refractory Esophageal Cancer

Study Start Date :

Jul 1, 2000

Actual Study Completion Date :

Aug 1, 2007

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed squamous cell carcinoma or adenocarcinoma of the esophagus or carcinoma of the gastroesophageal (GE) junction
If tumor extends below the GE junction into the proximal stomach, 50% of the tumor must involve the esophagus or GE junction
No gastric cancers with only a minor involvement of the GE junction or distal esophagus
Metastatic or locally advanced disease that is considered surgically unresectable
Must have failed a prior chemotherapy regimen that included paclitaxel for metastatic disease OR
Failed prior combination taxane-based chemotherapy and radiotherapy for locally advanced disease
Must have documented evidence of the following:
Disease progression while on taxane-based neoadjuvant or adjuvant therapy OR
Recurrent disease within 6 months of therapy
Measurable disease
Accurately measured in at least 1 dimension
At least 20 mm by conventional techniques OR
At least 10 mm by spiral CT scan
The following are considered nonmeasurable:
Bone lesions
Leptomeningeal disease
Ascites
Pleural/pericardial effusions
Inflammatory breast disease
Lymphangitis cutis/pulmonis
Abdominal masses that are not confirmed and followed by imaging techniques
Cystic lesions
No brain metastases

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

Karnofsky 70-100%

Life expectancy:

Not specified

Hematopoietic:

Absolute granulocyte count at least 1,500/mm^3
Platelet count at least 150,000/mm^3

Hepatic:

Bilirubin no greater than 1.5 mg/dL

Renal:

Creatinine no greater than 1.5 mg/dL

Cardiovascular:

No active angina or myocardial infarction within the past 6 months
No significant ventricular arrhythmia requiring antiarrhythmic medication
Atrial fibrillation that is well controlled on standard management allowed

Other:

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 2 months after study
No preexisting peripheral neuropathy of grade 2 or greater
No serious concurrent infection
No uncontrolled, nonmalignant medical illness that would preclude study
HIV negative
No other active malignancy within the past 5 years except:
Nonmelanoma skin cancer or
Carcinoma in situ of the cervix
History of T1a or T1b prostate cancer (detected incidentally during transurethral resection of the prostate and comprising less than 5% of resected tissue) allowed if PSA normal since surgery
No medical or psychiatric condition that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy:

No concurrent immunotherapy

Chemotherapy:

See Disease Characteristics
No more than 6 months since prior paclitaxel
No other concurrent chemotherapy

Endocrine therapy:

Not specified

Radiotherapy:

See Disease Characteristics
Prior radiotherapy allowed (indicator lesion must be outside of prior radiation port unless recent evidence of disease progression at that site)
No concurrent radiotherapy

Surgery:

See Disease Characteristics

Other:

No prior cyclin-dependent kinase or protein kinase C inhibitors for esophageal cancer
Recovered from toxic effects of any prior therapy
No concurrent vitamins, antioxidants or herbal preparations or supplements