Tipifarnib and Bortezomib in Treating Patients With Relapsed Multiple Myeloma

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

64 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-08-31

Brief Summary

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This phase I/II trial is studying the side effects and best dose of tipifarnib when given together with bortezomib and to see how well they work in treating patients with relapsed multiple myeloma. Tipifarnib and bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving tipifarnib together with bortezomib may kill more cancer cells.

Detailed Description

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OBJECTIVES: Primary I. Determine the maximum tolerated dose and dose-limiting toxicity of tipifarnib when administered with bortezomib in patients with relapsed multiple myeloma. (Phase I) II. Determine the response rate in patients treated with this regimen. (Phase II) III. Determine the toxicity profile of this regimen in these patients. (Phase II)

Secondary I. Determine the progression-free survival of patients treated with this regimen. (Phase II)

Tertiary I. Determine whether this regimen overcomes CAM-DR in primary myeloma cells and establish whether ex vivo efficacy predicts a clinical response in these patients.

II. Determine if activated Akt predicts clinical resistance and if levels of phosphorylated Akt are reduced by tipifarnib and bortezomib in these patients.

III. Determine whether molecular profiles from primary isolates (suspension vs adhered) correlate with clinical response in patients treated with this regimen.

OUTLINE: This is a phase I dose-escalation study of tipifarnib followed by a phase II study.

Phase I: Patients receive bortezomib IV on days 1, 4, 8, and 11 and oral tipifarnib twice daily on days 1-14. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of tipifarnib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. An additional 6 patients are treated at the MTD.

Phase II: Patients receive bortezomib as in phase I and tipifarnib as in phase I at the MTD.

After completion of study treatment, patients are followed every 3 months.

PROJECTED ACCRUAL: Approximately 52-64 patients will be accrued for this study.

Conditions

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Refractory Multiple Myeloma Stage II Multiple Myeloma Stage III Multiple Myeloma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (bortezomib, tipifarnib)

Phase I: Patients receive bortezomib IV on days 1, 4, 8, and 11 and oral tipifarnib twice daily on days 1-14. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of tipifarnib until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. An additional 6 patients are treated at the MTD.

Phase II: Patients receive bortezomib as in phase I and tipifarnib as in phase I at the MTD.

Group Type EXPERIMENTAL

bortezomib

Intervention Type DRUG

Given IV

tipifarnib

Intervention Type DRUG

Given orally

laboratory biomarker analysis

Intervention Type OTHER

Correlative studies

Interventions

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bortezomib

Given IV

Intervention Type DRUG

tipifarnib

Given orally

Intervention Type DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Diagnosis of multiple myeloma

* Stage II or III disease
* Relapsed disease after ≥ 2 prior therapies\*, confirmed by the presence of 1 of the following:

* New lytic lesion
* A 25% increase in urine or serum monoclonal protein
* Patients who received prior bortezomib must have responded to therapy
* Measurable disease, defined by 1 or more of the following criteria:

* Serum M-component ≥ 1.0 g/dL by serum protein electrophoresis
* Urine M-protein excretion \> 200 mg per 24-hour collection, by urine protein electrophoresis
* Performance status - Karnofsky 60-100%
* More than 8 weeks
* Platelet count ≥ 100,000/mm\^3
* Absolute neutrophil count ≥ 1,000/mm\^3
* Bilirubin ≤ 2 mg/dL
* Direct bilirubin ≤ 2 times upper limit of normal (ULN)
* AST or ALT ≤ 2 times ULN
* Creatinine ≤ 1.5 times ULN
* Calcium ≤ 12 mg/dL
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* Able to swallow study medication
* Capable of following directions regarding study medication, or has a daily caregiver who will be responsible for administering study medication
* No peripheral neuropathy ≥ grade 2
* No hypersensitivity to any of the following:

* Bortezomib
* Boron
* Mannitol
* Imidazole compounds (e.g., clotrimazole, ketoconazole, miconazole, econazole)
* No serious medical or psychiatric illness that would preclude study compliance
* No other life-threatening illness (unrelated to tumor)
* No other active or invasive malignancy within the past 3 years except for nonmelanoma skin cancer
* No serious infection
* No prior allogeneic bone marrow transplantation
* More than 30 days since prior and no concurrent immunotherapy
* More than 30 days since prior and no concurrent cytotoxic chemotherapy
* More than 14 days since prior high-dose corticosteroids
* No concurrent therapeutic corticosteroids (e.g., \> 10 mg prednisone per day)
* No concurrent hormonal therapy
* No concurrent antiemetic corticosteroids
* More than 14 days since prior and no concurrent radiotherapy
* More than 1 year since prior bortezomib
* More than 14 days since prior investigational drugs
* No prior tipifarnib
* No other concurrent cancer-related treatment
* No concurrent administration of the following enzyme-inducing anti-epileptic drugs:

* Phenytoin
* Phenobarbital
* Carbamazepine
* No concurrent magnesium- or aluminum-based antacids within 2 hours before or after tipifarnib administration
* Concurrent pamidronate or other bisphosphonates allowed

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Darrin Beaupre

Role: PRINCIPAL_INVESTIGATOR

H. Lee Moffitt Cancer Center and Research Institute

Locations

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H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Site Status

Countries

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United States

Other Identifiers

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NCI-2012-02675

Identifier Type: -

Identifier Source: org_study_id