A Phase 1 interventional study of Vismodegib and Pharmacological Study in DS Stage I Plasma Cell Myeloma, DS Stage II Plasma Cell Myeloma and DS Stage III Plasma Cell Myeloma, sponsored by National Cancer Institute (NCI). Completed at 2 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2014-12-23.
Sponsored by National Cancer Institute (NCI) · Phase 1, Interventional, and Treatment
This phase I trial studies how well vismodegib after stem cell transplant works in treating patients with high-risk first remission or relapsed multiple myeloma. Vismodegib may slow the growth of cancer cells. Giving vismodegib after autologous stem cell transplant may kill more multiple myeloma cells.
PRIMARY OBJECTIVES:
I. To determine if GDC-0449 (vismodegib) is able to reduce myeloma cancer stem cells (CSC) when given to patients with multiple myeloma (MM) following autologous stem cell transplantation.
SECONDARY OBJECTIVES:
I. To determine whether GDC-0449 is inhibiting the hedgehog (Hh) pathway in patients with MM following autologous transplantation by measuring downstream targets of Hh using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) on plasma cells and MM CSC obtained from blood and bone marrow of patients undergoing treatment.
II. To determine whether changes in MM CSC as measured by clonogenic assays on bone marrow are seen in response to GDC-0449 and whether these changes predict recurrence.
III. To determine whether changes in MM CSC can be measured with similar or better accuracy using peripheral blood flow cytometry as compared to bone marrow clonogenic assays.
IV. To determine the safety and toxicity profile for treatment with GDC-0449 following autologous transplantation in patients with high risk or relapsed MM.
V. To characterize the pharmacokinetics (PK) of GDC-0449 (total and unbound) at steady-state and correlate this with pharmacodynamic (PD) endpoints.
VI. To determine the one year progression free survival for patients given GDC-0449 following autologous transplantation.
OUTLINE:
Patients receive vismodegib orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 11 courses in the absence of disease progression or unacceptable toxicity.
After completion of treatment, patients are followed up for 4 weeks.
3,632 studies on the registry are indexed under Multiple Myeloma; 745 are open to participants now.
This study's enrollment of 50 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.
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Inclusion Criteria:
Women of child-bearing potential and men must use two forms of contraception (i.e., barrier contraception and one other method of contraception) at least 4 weeks prior to GDC-0449 treatment, for the duration of study participation, and for at least 12 months post-treatment; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
Women of childbearing potential are defined as follows:
Women are considered not to be of childbearing potential for the following reasons:
Patients receive vismodegib PO QD on days 1-28. Treatment repeats every 28 days for up to 11 courses in the absence of disease progression or unacceptable toxicity.
Drug: Vismodegib · Other: Pharmacological Study · Other: Laboratory Biomarker Analysis
Given PO
Also known as: Erivedge, GDC-0449, Hedgehog Antagonist GDC-0449
Correlative studies
Also known as: pharmacological studies
Correlative studies
Change in MM CSC counts
Estimated using a simple linear regression model. The proportion of patients with negative slope estimates, indicating decline in MM CSC counts over study evaluations will be estimated.
Time frame: Baseline to 6 months
Pharmacokinetics of vismodegib
Time frame: Days 1 and 15
Pharmacodynamics of vismodegib
Time frame: Up to 4 weeks after completion of study treatment
Time to progression
Estimated based on Kaplan-Meier and compared using the nonparametric, log-rank test, with proportional hazards regression used to model the effect of other correlations on the outcome of progression free survival (PFS). Median PFS will reported along with hazard ratios and corresponding 95% confidence intervals.
Time frame: From treatment initiation to the date of progression, assessed up to 4 weeks after completion of study treatment
This study is completed, as verified in Sep 2014. You cannot join it, but the record below documents what was studied.
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National Cancer Institute (NCI)