Temozolomide Plus PEG-Interferon Alfa-2B in Treating Patients With Advanced Solid Tumors

OBJECTIVES:

- Determine the safety and tolerability of temozolomide and PEG-interferon alfa-2b in
patients with advanced refractory solid tumors or chemotherapy-naive advanced cancer.

- Determine the maximum tolerated dose (MTD) and dose-limiting toxicity of this regimen in
this patient population.

- Determine the pharmacokinetics of PEG-interferon alfa-2b at the MTD when administered
with temozolomide in this patient population.

- Determine the anti-tumor activity of this regimen in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive oral temozolomide on days 1-7 and 15-21 and PEG-interferon alfa-2b
subcutaneously on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of
disease progression or unacceptable toxicity.

Cohorts of 1-9 patients receive escalating doses of temozolomide and PEG-interferon alfa-2b
until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose
preceding that at which at least 2 of 3 or 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: A maximum of 24 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

- Histologically confirmed advanced solid tumor that is refractory to standard therapy
OR

- Histologically confirmed chemotherapy-naive advanced cancer for which no curative
therapy or higher priority palliative chemotherapy exists

- Brain metastasis allowed

- No bone marrow involvement of tumor

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Performance status:

- ECOG 0-2

Life expectancy:

- Not specified

Hematopoietic:

- Absolute neutrophil count greater than 1,500/mm^3 AND/OR

- Platelet count greater than 100,000/mm^3

Hepatic:

- ALT or AST less than 3 times upper limit of normal (ULN) (5 times ULN if liver
metastases present)

- No autoimmune hepatitis

Renal:

- Creatinine less than 2.5 times ULN

Cardiovascular:

- No severe coronary artery disease

- No congestive heart failure

Pulmonary:

- No severe chronic obstructive pulmonary disease

Gastrointestinal:

- No frequent vomiting

- No medical condition that would interfere with oral medication intake (e.g., partial
bowel obstruction, partial intestinal bypass, or external biliary diversion)

Other:

- 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

- No known or suspected hypersensitivity to imidazotetrazin, interferon alfa, or any
excipient or vehicle included in the formulation or delivery system of study drug

- No history of autoimmune disease

- No preexisting severe psychiatric condition or history of severe psychiatric disorder
(including suicidal ideation or attempt)

- No life-threatening condition or severe preexisting condition

- No uncontrolled thyroid abnormalities

- No nonmalignant systemic disease

- No active uncontrolled infection

- HIV negative

- No AIDS-related illness

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- At least 3 weeks since prior biologic agents (e.g., bi-specific antibodies,
interleukin-2, or interferon) and recovered (excluding alopecia)

- No prior allogeneic, syngeneic, or autologous bone marrow or stem cell transplantation

- No other concurrent biologic therapy

- No concurrent colony stimulating factors or epoetin alfa for the prevention of
myelotoxicity

Chemotherapy:

- See Disease Characteristics

- At least 4 weeks since prior chemotherapy (more than 6 weeks for nitrosoureas,
melphalan, or mitomycin) and recovered (excluding alopecia)

- No prior high-dose chemotherapy and stem cell transplantation

- No more than 3 prior chemotherapy regimens

- No other concurrent chemotherapy

Endocrine therapy:

- Not specified

Radiotherapy:

- At least 6 weeks since prior wide-field radiotherapy to at least 25% of bone marrow
(e.g., pelvic radiotherapy)

- More than 6 weeks since prior strontium chloride Sr 89 or samarium Sm 153 lexidronam
pentasodium

- Recovered from prior radiotherapy (excluding alopecia)

- No concurrent radiotherapy

Surgery:

- At least 4 weeks since prior major surgery

- At least 1 week since prior minor surgery

Other:

- At least 4 weeks since prior investigational therapy