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

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: FTI	Phase 2

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.

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

44 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase II Evaluation of FTI (R115777) (NSC 702818) in Treatment of Advanced Multiple Myeloma

Study Start Date :

Jan 1, 2001

Actual Primary Completion Date :

Sep 1, 2003

Actual Study Completion Date :

Jan 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: FTI Other Names: R115777 NSC702818 FTase Inhibitor Tipifarnib Zarnestra farnesyl transferase inhibitor

Arm

Intervention/Treatment

Experimental: 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.

Drug: FTI

Other Names:

R115777

NSC702818

FTase Inhibitor

Tipifarnib

Zarnestra

farnesyl transferase inhibitor

Outcome Measures

Primary Outcome Measures

Objective Response Rate (ORR) [26 months]
The primary end point of the study is to determine the rate of objective response and disease stabilization. Responses were to be defined according to modified Southwest Oncology Group (SWOG) criteria. Disease progression was defined as a 25% increase in the serum M-component confirmed by a second measurement obtained within 1 to 4 weeks of the first measurement, or an increase in the 24-hour urine M-component by more than 50%, confirmed by a second measurement. Other criteria for disease progression included the need to administer radiotherapy, new lytic bone lesions, enlargement of existing bone lesions, or new soft tissue plasmacytomas.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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