T900607 in Treating Patients With Unresectable Liver Cancer

A Phase II Study Of Intravenous T900607-Sodium In Subjects With Chemotherapy-Naive Unresectable Hepatocellular Carcinoma

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of T900607 in treating patients who have unresectable liver cancer.

OBJECTIVES:

• Determine the complete and partial response rates of patients with chemotherapy-naïve unresectable hepatocellular carcinoma treated with T900607.
• Determine the efficacy of this drug, in terms of duration of response and time to disease progression, in these patients.
• Determine the pharmacokinetics of this drug in these patients.
• Determine the safety profile of this drug in these patients.

OUTLINE: This is a multicenter study.

Patients receive T900607 IV over 1 hour once weekly. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 20-35 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed unresectable hepatocellular carcinoma (HCC)
• Bidimensionally measurable disease defined as at least 1 lesion that is 1 cm or more in 2 dimensions by CT scan
• Class A or B Child-Pugh liver classification
• No prior CNS metastases or carcinomatous meningitis

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 70-100%

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3*
• Platelet count at least 100,000/mm^3*
• Hemoglobin at least 8.5 g/dL* NOTE: *More than 7 days since prior blood transfusions or growth factors

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• Albumin greater than 2.5 g/dL
• AST and ALT no greater than 3 times ULN
• INR no greater than 1.5 (unless receiving anticoagulants)

Renal

• Creatinine no greater than 2 times ULN

Cardiovascular

• LVEF at least 50%
• No New York Heart Association class III or IV cardiac disease
• No acute anginal symptoms

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study
• No severe concurrent disease, infection, or co-morbidity that would preclude study entry
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior immunotherapy for HCC
• No concurrent therapeutic biological response modifier

Chemotherapy

• No prior chemotherapy for HCC
• No prior chemoembolization for HCC
• No other concurrent cytotoxic chemotherapy

Endocrine therapy

• At least 6 weeks since prior hormonal therapy (an indicator lesion must exist outside the area of therapy
• No concurrent hormonal anticancer therapy

Radiotherapy

• No prior radiotherapy for HCC
• At least 6 weeks since prior radiofrequency ablation, selective internal radiation, or embolization (an indicator lesion must exist outside the area of therapy)
• No concurrent radiotherapy (including palliative therapy)

Surgery

• At least 6 weeks since prior surgical resection (an indicator lesion must exist outside the area of therapy)

  • Recurrence at the margin of the surgical resection is allowed

• At least 6 weeks since prior cryosurgery

• More than 4 weeks since other prior major surgery

Other

• More than 4 weeks since prior investigational therapy
• At least 6 weeks since prior intratumoral ethanol injection (an indicator lesion must exist outside the area of therapy)
• No other concurrent investigational anticancer therapy