Phase II Evaluation of FTase Inhibitor (FTI)in Treatment of Advanced Multiple Myeloma

NCT ID: NCT00012350

Last Updated: 2012-10-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-01-31
• Study Completion Date: 2010-01-31

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of R115777 in treating patients who have relapsed or refractory multiple myeloma.

Detailed Description

OBJECTIVES: I. Determine the rate of objective response and disease stabilization in patients with relapsed or refractory multiple myeloma treated with R115777. II. Determine whether the degree of inhibition of FTase activity and farnesylation of lamin-B, H-, K-, and N-RAS in peripheral blood mononuclear cells and tumor tissue correlates with tumor response in patients treated with this regimen. III. Determine whether the presence of activating RAS mutations in myeloma cells predicts treatment response in patients treated with this regimen. IV. Correlate R115777 plasma levels and RAS mutation status with tumor response in patients treated with this regimen.

OUTLINE: Patients receive oral R115777 twice daily on days 1-21. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients are followed for at least 30 days.

PROJECTED ACCRUAL: Approximately 12-42 patients will be accrued for this study within 25 months.

Conditions

Multiple Myeloma

Keywords

refractory multiple myeloma; stage II multiple myeloma; stage III multiple myeloma; plasma cell neoplasm

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Oral FTI (R115777) Treatment

Patients will be administered oral FTI (R115777) at a dose of 300-mg by mouth (PO) twice a day (BID). Drug will be taken without regard to meals.

The study regimen will consist of 3 weeks of treatment followed by one week off for a total cycle duration of 4 weeks.

Group Type: EXPERIMENTAL

FTI

Intervention Type: DRUG

Interventions

FTI

Intervention Type: DRUG

Other Intervention Names

R115777; NSC702818; FTase Inhibitor; Tipifarnib; Zarnestra; farnesyl transferase inhibitor

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS: Diagnosis of relapsed or refractory multiple myeloma confirmed by the presence of the following: Bone marrow plasmacytosis with at least 10 percent plasma cells Sheets of plasma cells OR Biopsy-proven plasmacytoma Documentation of at least one of the following criteria: Serum myeloma (M)-protein component at least 1.0 g/dL by serum protein electrophoresis Urine M-protein excretion more than 200 mg/24 hours by urine protein electrophoresis Stage IIA or IIIA disease Measurable disease The following are not considered measurable disease: Lytic bone lesions Anemia Bone marrow plasmacytosis Beta-2 microglobulin in serum Previously treated with conventional chemotherapy Progressing or relapsing disease at time of study

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Eastern Cooperative Oncology Group (ECOG) 0-3 Life expectancy: More than 8 weeks Hematopoietic: Absolute neutrophil count at least 1,000/mm^3 Hepatic: aspartate aminotransferase (AST) or alanine transaminase (ALT) no greater than 2 times upper limit of normal (ULN) Bilirubin no greater than 2 mg/dL Renal: Creatinine no greater than 1.5 times ULN Calcium no greater than 12 mg/dL Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Capable of swallowing intact study medication tablets No concurrent serious infection No grade 3 or greater peripheral neuropathy No life-threatening illness unrelated to tumor No other active or invasive cancer within the past 3 years except nonmelanoma skin cancer

PRIOR CONCURRENT THERAPY: Biologic therapy: Prior thalidomide allowed At least 14 days since prior immunologic agents No concurrent immunologic agents Chemotherapy: See Disease Characteristics At least 3 weeks since prior cytotoxic chemotherapy No other concurrent cytotoxic therapy Endocrine therapy: At least 14 days since prior high-dose corticosteroids No concurrent hormonal therapy No concurrent corticosteroids Radiotherapy: At least 3 weeks since prior radiotherapy and recovered No concurrent radiotherapy Surgery: Not specified Other: No other concurrent cancer therapy Concurrent pamidronate or other bisphosphonates allowed

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

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

H. Lee Moffitt Cancer Center and Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Melissa Alsina, M.D.

Role: PRINCIPAL_INVESTIGATOR

H. Lee Moffitt Cancer Center and Research Institute

Locations

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Countries

United States

Other Identifiers

NIH-2030

Identifier Type: OTHER

Identifier Source: secondary_id

MCC-12516

Identifier Type: -

Identifier Source: org_study_id

NCT00021203

Identifier Type: -

Identifier Source: nct_alias