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.

Condition	Treatment or Intervention	Phase
unspecified adult solid tumor, protocol specific	Procedure: chemotherapy  Procedure: biological response modifier therapy  Procedure: interferon therapy  Procedure: growth factor antagonist therapy  Procedure: cytokine therapy  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Drug: PEG-interferon alfa-2b  Drug: temozolomide	Phase I

Further Study Details: 

OBJECTIVES: I. Determine the safety and tolerability of temozolomide and PEG-interferon alfa-2b in patients with advanced refractory solid tumors or chemotherapy-naive advanced cancer. II. Determine the maximum tolerated dose (MTD) and dose-limiting toxicity of this regimen in this patient population. III. Determine the pharmacokinetics of PEG-interferon alfa-2b at the MTD when administered with temozolomide in this patient population. IV. Determine the anti-tumor activity of this regimen in these patients.

PROTOCOL 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.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--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

--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

--Patient Characteristics--

Age: 18 and over

Performance status: ECOG 0-2

Life expectancy: Not specified

Hematopoietic:

• Absolute neutrophil count greater than 1,500/mm3 AND/OR
• Platelet count greater than 100,000/mm3

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

New Hampshire
      Norris Cotton Cancer Center, Lebanon,  New Hampshire,  03756-0002,  United States

Study chairs or principal investigators

Lionel D. Lewis,  Study Chair,  Norris Cotton Cancer Center   

Study ID Numbers:  CDR0000068523; DMS-0010; NCI-G01-1924
Record last reviewed:  July 2003
Last Updated:  October 13, 2004
Record first received:  April 10, 2001
ClinicalTrials.gov Identifier:  NCT00014261
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08