Protocol Number: 02-C-0083

Title:

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

Number:

02-C-0083

Summary:

CC-5013 (Revamid™ (Trademark)), a modified form of thalidomide, has been shown to have some effect in reducing tumors in laboratory animals. A small number of studies in humans have shown that oral doses of the drug reduce tumors in some patients with cancer and have few adverse side effects.

This study seeks to find the maximum tolerated dose (MTD) of CC-5013, characterize its pharmacokinetic profile, and characterize its side effect profile. A secondary goal is to evaluate its effect in reducing tumors.

The study will enroll up to 24 adult patients (over age 18) with solid tumors and/or lymphoma that are not responding to other treatments. They must have a life expectancy of more than 3 months and have been off other treatments for their cancer for at least 4 weeks before beginning to receive CC-5013. Pregnant or nursing women will not be enrolled, and all patients must use contraception during treatment and for 2 months following the end of treatment.

Four weeks before treatment begins, baseline imaging studies of the tumors will be done (CT scan, bone scan, MRI, or PET scan, as appropriate). Blood and urine samples will be taken 7 days before treatment begins.

Patients will receive increasing doses of oral CC-5013 until the MTD is defined. The first day's dose will be 25 mg. For the next 28 days, the dose will be 50 mg per day. A dosing cycle is 28 days (excluding the first day). The dose will be increased to 75 mg per day for the second cycle, 100 mg per day for the third cycle, and 150 mg per day for the fourth cycle (assuming MTD has not been reached by that point). The first dose will be given at the NIH Clinical Center, and patients will stay at the Clinical Center for approximately 24 hours. The remaining doses can be taken on an outpatient basis.

Blood samples to determine toxicity levels will be taken 7 times on day 1; twice on day 2, and twice on day 3. Blood and urine samples will be taken during follow-up clinic visits every 2 weeks through cycle 3 and monthly thereafter. Patients will be asked to report any side effects and any medicines they take, whether prescription or over the counter, since not all side effects or interactions of CC-5013 are known. Restaging of the disease through imaging studies will be done after every 2 months of treatment to determine the drug's effectiveness in treating the cancer.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

All patients with refractory solid tumors and/or lymphoma are eligible according to the criteria listed below.

Patients must have histopathological documentation of cancer confirmed in the Laboratory of Pathology/NCI of the Clinical Center at the National Institutes of Health or the National Naval Medical Center or Walter Reed Army Medical Center prior to starting this study.

Patient must be ECOG performance status of less than or equal to 2.

Patients must have a life expectancy of more than 3 months.

Hematological eligibility parameters (within 1 week of starting therapy):

Granulocyte count greater than 1,500/mm(3).

Platelet count greater than 100,000/mm(3).

If the creatinine is greater than 1.5 mg/dL, obtain a 24 hour urine collection. Creatinine clearance must be greater than 60 mL/min.

Hepatic function: normal bilirubin (total); ALT less than 2.5 x normal; AST less than 2.5 x normal.

Patients must have recovered from any acute toxicity related to prior therapy, including surgery.

Patients must be off prior chemotherapy, hormonal therapy, radiation therapy, or biological therapy for at least 4 weeks prior to starting study medication and must have recovered from all acute side effects prior to initiation of CC-5013. Patients who were receiving mitomycin C, nitrosoureas, or carboplatin must be 6 weeks from the last administration of chemotherapy. Patients with prostate cancer must continue to receive LHRH agonist (unless orchiectomy has been done).

Patients must not have an acute, critical illness, including a serious untreated infection.

Patients must be willing to travel from their home to the NIH for follow-up visits.

All patients of childbearing capability will be required to use contraception during treatment and for two months after the completion of CC-5013 treatment. Women of childbearing capability must have a negative pregnancy test.

Patients must be able to understand and sign the informed consent form.

Patients must be greater than 18 years of age or older.

EXCLUSION CRITERIA:

Patients with brain metastases or primary CNS malignancies.

Patients who are pregnant or lactating.

Patients who are currently taking anticonvulsants (phenobarbital, phenytoin, carbamazepine). Patients taking rifampin will also be excluded. We do not know the metabolic enzymes responsible for CC5013 elimination, but thalidomide does undergo CYP3A4. There are potential drug interactions between CC-5013 and these classes of drugs.

Patients with a history of unstable or newly diagnosed angina pectoris, recent myocardial infarction (within 6 months of enrollment), New York class II-IV congestive heart failure, chronic obstructive lung disease requiring oxygen therapy or uncontrolled seizure activity are not eligible.

Special Instructions: Currently Not Provided

Keywords:

Angiogenesis

Phase I

Pharmacokinetic

Cancer

New Drug

Recruitment Keywords:

Cancer

Tumor

Metastatic Cancer

Lymphoma

Conditions:

Neoplasm

Investigational Drug(s):

CC5013

Investigational Device(s):

None

Contacts:

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:

Stevens RJ, Andujar C, Edwards CJ, Ames PR, Barwick AR, Khamashta MA, Hughes GR. Thalidomide in the treatment of the cutaneous manifestations of lupus erythematosus: experience in sixteen consecutive patients. Br J Rheumatol. 1997 Mar;36(3):353-9. PMID: 9133968

Sampaio EP, Kaplan G, Miranda A, Nery JA, Miguel CP, Viana SM, Sarno EN. The influence of thalidomide on the clinical and immunologic manifestation of erythema nodosum leprosum. J Infect Dis. 1993 Aug;168(2):408-14. PMID: 8335978

Vogelsang GB, Farmer ER, Hess AD, Altamonte V, Beschorner WE, Jabs DA, Corio RL, Levin LS, Colvin OM, Wingard JR, et al. Thalidomide for the treatment of chronic graft-versus-host disease. N Engl J Med. 1992 Apr 16;326(16):1055-8. PMID: 1549151

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