A Phase 1/2 interventional study of bortezomib and tipifarnib in Refractory Multiple Myeloma, Stage II Multiple Myeloma and Stage III Multiple Myeloma, sponsored by National Cancer Institute (NCI). Terminated at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2013-10-08.
Sponsored by National Cancer Institute (NCI) · Phase 1/2, Interventional, and Treatment
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.
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.
3,632 studies on the registry are indexed under Multiple Myeloma; 745 are open to participants now.
This study's planned enrollment of 64 is above the median of 41 across 2,907 interventional studies indexed under Multiple Myeloma.
Browse Multiple Myeloma studies →National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.
Of its 402 completed or terminated interventional studies of FDA-regulated products, 365 (91%) have results posted.
Counted across the registry records on this site, refreshed daily.
Inclusion Criteria:
Diagnosis of multiple myeloma
Relapsed disease after ≥ 2 prior therapies*, confirmed by the presence of 1 of the following:
Measurable disease, defined by 1 or more of the following criteria:
No hypersensitivity to any of the following:
No concurrent administration of the following enzyme-inducing anti-epileptic drugs:
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.
Drug: bortezomib · Drug: tipifarnib · Other: laboratory biomarker analysis
Given IV
Given orally
Correlative studies
Maximum tolerated dose of tipifarnib as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0 (phase I)
Time frame: Up to day 21
Response rate (complete response [CR] + partial response [PR]) determined using the Bladé Response criteria (phase II)
Exact 95% confidence intervals constructed.
Time frame: Up to 6 weeks
Toxicities, graded according to the NCI CTCAE v3.0 (phase II)
Time frame: Up to 2 years
Proportion of patients overcoming CAM-DR
An exact 95% confidence interval for that proportion will be computed.
Time frame: Prior to therapy
Proportion of patients overcoming CAM-DR
An exact 95% confidence interval for that proportion will be computed.
Time frame: Day 11 of course 1
Relationship of overcoming CAM-DR and clinical response
Compared using a chi-square contingency table test at the two-sided 0.05 significance level.
Time frame: Prior to therapy
Relationship of overcoming CAM-DR and clinical response
Compared using a chi-square contingency table test at the two-sided 0.05 significance level.
Time frame: Day 11 of course 1
Clinical resistance and levels of phosphorylated Akt
P-Akt levels both pre and post treatment will be obtained and compared using a paired t test. Logistic regression will be used with P-Akt activity as independent variable in a logistic regression modeling probability of response. Odds ratio indicating change in odds of response associated with a unit change in P-Akt level will be computed as well as a 95% confidence interval for that odds ratio.
Time frame: Prior to therapy
Clinical resistance and levels of phosphorylated Akt
P-Akt levels both pre and post treatment will be obtained and compared using a paired t test. Logistic regression will be used with P-Akt activity as independent variable in a logistic regression modeling probability of response. Odds ratio indicating change in odds of response associated with a unit change in P-Akt level will be computed as well as a 95% confidence interval for that odds ratio.
Time frame: Day 11 of course 1
Correlation of molecular profiles from primary isolates with clinical response
Compared using paired t tests at the 0.05 significance level.
Time frame: Prior to therapy
Correlation of molecular profiles from primary isolates with clinical response
Compared using paired t tests at the 0.05 significance level.
Time frame: Day 11 of course 1
Progression-free survival (phase II)
Summarized with Kaplan-Meier curve and related statistics.
Time frame: Up to 2 years
This study is terminated, as verified in Oct 2013. You cannot join it, but the record below documents what was studied.
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National Cancer Institute (NCI)