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

October 22, 2012 updated by: H. Lee Moffitt Cancer Center and Research Institute

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

44

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Tampa, Florida, United States, 33612
        • H. Lee Moffitt Cancer Center and Research Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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
  • Zarnestra
  • Tipifarnib
  • NSC702818
  • FTase Inhibitor
  • farnesyl transferase inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: 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.
26 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

H. Lee Moffitt Cancer Center and Research Institute

Collaborators

National Cancer Institute (NCI)
National Institutes of Health (NIH)

Investigators

  • Principal Investigator: Melissa Alsina, M.D., H. Lee Moffitt Cancer Center and Research Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2001

Primary Completion (Actual)

September 1, 2003

Study Completion (Actual)

January 1, 2010

Study Registration Dates

First Submitted

March 3, 2001

First Submitted That Met QC Criteria

May 19, 2004

First Posted (Estimate)

May 20, 2004

Study Record Updates

Last Update Posted (Estimate)

October 23, 2012

Last Update Submitted That Met QC Criteria

October 22, 2012

Last Verified

October 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MCC-12516
  • NIH-2030 (Other Identifier: NIH)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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