Status and phase
Conditions
Treatments
Study type
Funder types
Identifiers
About
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.
Full description
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.
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
Inclusion Criteria:
Diagnosis of multiple myeloma
Relapsed disease after ≥ 2 prior therapies*, confirmed by the presence of 1 of the following:
Patients who received prior bortezomib must have responded to therapy
Measurable disease, defined by 1 or more of the following criteria:
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:
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:
No concurrent magnesium- or aluminum-based antacids within 2 hours before or after tipifarnib administration
Concurrent pamidronate or other bisphosphonates allowed
Primary purpose
Allocation
Interventional model
Masking
64 participants in 1 patient group
Loading...
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal