Irinotecan and Flavopiridol in Treating Patients With Advanced Liver Cancer

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00087282

Collaborator

National Cancer Institute (NCI) (NIH)

Location

Duration (Months)

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as irinotecan and flavopiridol, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving irinotecan together with flavopiridol works in treating patients with advanced liver cancer.

Condition or Disease	Intervention/Treatment	Phase
Liver Cancer	Drug: alvocidib Drug: irinotecan hydrochloride	Phase 2

Detailed Description

OBJECTIVES:

Primary

Determine the time to progression in patients with advanced hepatocellular carcinoma treated with irinotecan and flavopiridol.

Secondary

Determine the response rate and overall survival in patients treated with this regimen.
Determine the toxicity of this regimen in these patients.

OUTLINE: This is an open-label, non-randomized study.

Patients receive irinotecan IV over 30 minutes and flavopiridol IV over 1 hour on days 1, 8, 15, and 22. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 16-32 patients will be accrued for this study within 2 years.

Study Design

Study Type:

Interventional

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Non-Randomized Phase II Study of Sequential Irinotecan (CPT-11) And Flavopiridol In Patients With Advanced Hepatoma

Study Start Date :

Jun 1, 2004

Actual Study Completion Date :

Jul 1, 2006

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 or cytologically confirmed hepatocellular carcinoma
Advanced disease
Measurable disease
At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
Prior local therapy (e.g., surgery, hepatic arterial embolization, radiofrequency ablation, or cryoablation) allowed provided therapy was completed ≥ 8 weeks before study entry AND ≥ 1 of the following conditions are met:
Target lesion was not subjected to local therapy
25% increase in the size of target lesion within the field of prior local therapy
Lesions treated with external beam radiotherapy are not acceptable as target lesions
Child-Pugh class A or B status if liver cirrhosis is present
Score 7 or 8 only
No known brain metastases

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

Karnofsky 70-100%

Life expectancy

Not specified

Hematopoietic

Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 75,000/mm^3
WBC ≥ 3,000/mm^3

Hepatic

See Disease Characteristics
AST and ALT ≤ 2.5 times upper limit of normal
Bilirubin ≤ 1.5 mg/dL

Renal

Creatinine normal OR
Creatinine clearance ≥ 60 mL/min

Cardiovascular

No symptomatic congestive heart failure
No unstable angina pectoris
No deep vein thrombosis within the past 6 months
Patients maintained on anticoagulation therapy for an event that occurred more than 6 months ago are eligible
No myocardial infarction within the past 6 months
No cardiac arrhythmia within the past 6 months
Rate-controlled atrial fibrillation allowed if stable for at least 6 months

Pulmonary

No pulmonary embolus within the past 6 months
Patients maintained on anticoagulation therapy for an event that occurred more than 6 months ago are eligible

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 3 months after study participation
No prior allergic reaction attributed to compounds of similar chemical or biological composition to flavopiridol or irinotecan
No clinically significant gastrointestinal bleeding requiring hospitalization within the past month
No active or ongoing infection
No psychiatric illness or social situation that would preclude study compliance
No other uncontrolled illness
No other malignancy within the past 3 years except carcinoma in situ of the cervix, adequately treated basal cell skin cancer, or superficial bladder tumors [Ta, Tis, or T1]

PRIOR CONCURRENT THERAPY:

Biologic therapy

No prior systemic biologic therapy

Chemotherapy

No prior systemic chemotherapy for hepatocellular carcinoma
No other concurrent chemotherapy

Endocrine therapy

Not specified

Radiotherapy

See Disease Characteristics

Surgery

See Disease Characteristics
No prior organ allograft

Other

No concurrent combination antiretroviral therapy for HIV-positive patients
No concurrent vitamins, antioxidants, or herbal preparations and supplements
Single-tablet multivitamin allowed
No other concurrent investigational agents
No other concurrent anticancer agents or therapies

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021

Sponsors and Collaborators

Memorial Sloan Kettering Cancer Center
National Cancer Institute (NCI)

Investigators

Principal Investigator: Ghassan Abou-Alfa, MD, Memorial Sloan Kettering Cancer Center
Principal Investigator: Gary K. Schwartz, MD, Memorial Sloan Kettering Cancer Center