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

NCT ID: NCT00014261

Last Updated: 2018-03-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-10-31
• Study Completion Date: 2002-11-30

Brief Summary

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.

Detailed Description

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.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Study Design

• Primary Study Purpose: TREATMENT

Interventions

PEG-interferon alfa-2b

Intervention Type: BIOLOGICAL

temozolomide

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Dartmouth-Hitchcock Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Lionel.D.Lewis, MD

Professor of Medicine and of Pharmacology and Toxicology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lionel D. Lewis, MD

Role: STUDY_CHAIR

Norris Cotton Cancer Center

Locations

Norris Cotton Cancer Center

Lebanon, New Hampshire, United States

Countries

United States

Other Identifiers

P30CA023108

Identifier Type: NIH

Identifier Source: secondary_id

View Link

DMS-0010

Identifier Type: -

Identifier Source: secondary_id

NCI-G01-1924

Identifier Type: -

Identifier Source: secondary_id

CDR0000068523

Identifier Type: -

Identifier Source: org_study_id