RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing
so they stop growing or die. PEG-interferon alfa-2B may interfere with the growth of cancer
cells. Combining temozolomide with PEG-interferon alfa-2B may be an effective treatment for
advanced solid tumors.
PURPOSE: Phase I trial to study the effectiveness of combining temozolomide and
PEG-interferon alfa-2B in treating patients who have advanced solid tumors.
- 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.
- Histologically confirmed advanced solid tumor that is refractory to standard therapy
- 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
- 18 and over
- ECOG 0-2
- Not specified
- Absolute neutrophil count greater than 1,500/mm^3 AND/OR
- Platelet count greater than 100,000/mm^3
- ALT or AST less than 3 times upper limit of normal (ULN) (5 times ULN if liver
- No autoimmune hepatitis
- Creatinine less than 2.5 times ULN
- No severe coronary artery disease
- No congestive heart failure
- No severe chronic obstructive pulmonary disease
- 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)
- 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:
- 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
- No other concurrent biologic therapy
- No concurrent colony stimulating factors or epoetin alfa for the prevention of
- 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
- Not specified
- 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
- Recovered from prior radiotherapy (excluding alopecia)
- No concurrent radiotherapy
- At least 4 weeks since prior major surgery
- At least 1 week since prior minor surgery
- At least 4 weeks since prior investigational therapy