CC-5013 in Treating Patients With Cancer That Has Not Responded to Previous Therapy

A Multidose Phase I Study of Oral CC5013, a Thalidomide Derivative, in Patients With Refractory Metastatic Cancer

RATIONALE: CC-5013 may stop the growth of cancer by stopping blood flow to the tumor.

PURPOSE: Phase I trial to study the effectiveness of CC-5013 in treating patients who have solid tumors and/or lymphoma that did not respond to previous therapy.

OBJECTIVES:

• Determine the maximum tolerated dose of CC-5013 in patients with refractory solid tumors and/or lymphoma.
• Characterize the pharmacokinetic profile of this drug in these patients.
• Determine whether any correlations can be made between plasma concentrations of this drug and toxicity or clinical activity or biological activity in these patients.
• Characterize the side effect profile of this drug in these patients.
• Determine the dose-limiting toxicity of this drug in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive oral CC-5013 on day 1. Within 4-10 days, patients begin second course and receive oral CC-5013 once daily on days 1-21. Subsequent courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of CC-5013 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 2 of 6 patients experience dose-limiting toxicity.

Patients are followed at 2 weeks.

PROJECTED ACCRUAL: A total of 3-51 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed refractory solid tumor and/or lymphoma
• No brain metastases or primary CNS malignancies

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• More than 3 months

Hematopoietic:

• Granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin normal
• ALT and AST less than 2.5 times normal

Renal:

• Creatinine no greater than 1.5 mg/dL OR
• Creatinine clearance greater than 60 mL/min

Cardiovascular:

• No unstable or newly diagnosed angina pectoris
• No myocardial infarction within the past 6 months
• No New York Heart Association class II, III, or IV congestive heart failure

Pulmonary:

• No chronic obstructive lung disease requiring oxygen therapy

Other:

• No uncontrolled seizures
• No concurrent acute critical illness
• No serious untreated infection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 2 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 4 weeks since prior biologic therapy

Chemotherapy:

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas, mitomycin, or carboplatin)
• No concurrent cytotoxic chemotherapy

Endocrine therapy:

• At least 4 weeks since prior hormonal therapy
• Concurrent luteinizing hormone-releasing hormone agonist required in patients with prostate cancer unless prior orchiectomy has been performed

Radiotherapy:

• At least 4 weeks since prior radiotherapy

Surgery:

• See Endocrine therapy
• Prior surgery allowed

Other:

• Recovered from prior therapy
• No concurrent anticonvulsants (e.g., phenobarbital, phenytoin, or carbamazepine)
• No concurrent rifampin
• No concurrent grapefruit juice