A Phase 1 interventional study of gamma-secretase/Notch signalling pathway inhibitor RO4929097 and diagnostic laboratory biomarker analysis in Unspecified Adult Solid Tumor, Protocol Specific, sponsored by National Cancer Institute (NCI). Completed at 3 sites in Canada. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2014-04-02.
Sponsored by National Cancer Institute (NCI) · Phase 1, Interventional, and Treatment
This phase I trial is studying the side effects, best way to give, and best dose of gamma-secretase inhibitor RO4929097 in treating patients with metastatic or unresectable solid malignancies. Enzyme inhibitors, such as gamma-secretase inhibitor RO4929097, may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVES:
I. To determine the safety profile of 6 different administration schedules of gamma-secretase inhibitor RO4929097 in patients with advanced solid malignancies.
SECONDARY OBJECTIVES:
I. To determine pharmacokinetic (PK) parameters of gamma-secretase inhibitor RO4929097 administered using 6 different administration schedules.
II. To assess the preliminary antitumor activity of gamma-secretase inhibitor RO4929097 in these patients.
TERTIARY OBJECTIVES:
I. To assess the pharmacodynamic (PD) effects of gamma-secretase inhibitor RO4929097 on Notch signaling pathway in tumor and surrogate tissues, as well as soluble markers of angiogenesis in plasma, when administered using 6 different dosing schedules. (Exploratory) II. To evaluate the relationship between PK and PD effects in an attempt to define the optimal biological dosing schedule (OBDS) that can provide a sustained inhibition of Notch signaling pathway over time with a tolerable toxicity profile. (Exploratory) III. To correlate inhibition of Notch signaling pathway measured in tumor and surrogate tissues with preliminary antitumor activity and assess the potential clinical predictive value of OBDS as defined above. (Exploratory) IV. To assess the effect of the various pharmacogenomic polymorphisms of the cytochrome P450 pathway on PK and PD parameters. (Exploratory)
OUTLINE: This is a multicenter, dose-escalation study. Patients are assigned to 1 of 6 dose schedules.
GROUP A: Patients receive oral gamma-secretase inhibitor RO4929097 once daily on days 1-3 and 8-10.
GROUP B: Patients receive oral RO4929097 once daily on days 1-7.
GROUP C: Patients receive oral RO4929097 once daily on days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, and 21.
GROUP D: Patients receive oral RO4929097 once daily on days 1, 8, and 15.
GROUP E: Patients receive oral RO4929097 once daily on days 1, 4, 8, 11, 15, and 18.
GROUP F: Patients receive oral RO4929097 once daily days 1-5, 8-12, and 15-19.
Treatment in all groups repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsies at baseline and between days 15 and 22 in the first course of treatment. Plasma samples are collected periodically for pharmacokinetic, pharmacodynamic, and pharmacogenomic analysis and to assess levels of adipsin and markers of angiogenesis.
After completion of study treatment, patients are followed up for 4 weeks.
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:
Histologically or cytologically confirmed solid malignancy
No uncontrolled concurrent illness including, but not limited to, any of the following:
No history of risk factors for QT interval prolongation including, but not limited to, a family or personal history of any of the following:
At least 4 weeks since prior radiotherapy or systemic therapy (6 weeks for prior carmustine or mitomycin C)
Patients receive oral gamma-secretase inhibitor RO4929097 once daily on days 1-3 and 8-10. Treatment in all groups repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsies at baseline and between days 15 and 22 in the first course of treatment. Plasma samples are collected periodically for pharmacokinetic, pharmacodynamic, and pharmacogenomic analysis and to assess levels of adipsin and markers of angiogenesis.
Drug: gamma-secretase/Notch signalling pathway inhibitor RO4929097 · Other: diagnostic laboratory biomarker analysis · Other: pharmacogenomic studies · Other: pharmacological study
Patients receive oral RO4929097 once daily on days 1-7. Treatment in all groups repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsies at baseline and between days 15 and 22 in the first course of treatment. Plasma samples are collected periodically for pharmacokinetic, pharmacodynamic, and pharmacogenomic analysis and to assess levels of adipsin and markers of angiogenesis.
Drug: gamma-secretase/Notch signalling pathway inhibitor RO4929097 · Other: diagnostic laboratory biomarker analysis · Other: pharmacogenomic studies · Other: pharmacological study
Patients receive oral RO4929097 once daily on days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, and 21. Treatment in all groups repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsies at baseline and between days 15 and 22 in the first course of treatment. Plasma samples are collected periodically for pharmacokinetic, pharmacodynamic, and pharmacogenomic analysis and to assess levels of adipsin and markers of angiogenesis.
Drug: gamma-secretase/Notch signalling pathway inhibitor RO4929097 · Other: diagnostic laboratory biomarker analysis · Other: pharmacogenomic studies · Other: pharmacological study
Patients receive oral RO4929097 once daily on days 1, 8, and 15. Treatment in all groups repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsies at baseline and between days 15 and 22 in the first course of treatment. Plasma samples are collected periodically for pharmacokinetic, pharmacodynamic, and pharmacogenomic analysis and to assess levels of adipsin and markers of angiogenesis.
Drug: gamma-secretase/Notch signalling pathway inhibitor RO4929097 · Other: diagnostic laboratory biomarker analysis · Other: pharmacogenomic studies · Other: pharmacological study
Patients receive oral RO4929097 once daily on days 1, 4, 8, 11, 15, and 18. Treatment in all groups repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsies at baseline and between days 15 and 22 in the first course of treatment. Plasma samples are collected periodically for pharmacokinetic, pharmacodynamic, and pharmacogenomic analysis and to assess levels of adipsin and markers of angiogenesis.
Drug: gamma-secretase/Notch signalling pathway inhibitor RO4929097 · Other: diagnostic laboratory biomarker analysis · Other: pharmacogenomic studies · Other: pharmacological study
Patients receive oral RO4929097 once daily days 1-5, 8-12, and 15-19. Treatment in all groups repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsies at baseline and between days 15 and 22 in the first course of treatment. Plasma samples are collected periodically for pharmacokinetic, pharmacodynamic, and pharmacogenomic analysis and to assess levels of adipsin and markers of angiogenesis.
Drug: gamma-secretase/Notch signalling pathway inhibitor RO4929097 · Other: diagnostic laboratory biomarker analysis · Other: pharmacogenomic studies · Other: pharmacological study
Also known as: R4733, RO4929097
Also known as: Pharmacogenomic Study
Also known as: pharmacological studies
Safety profile of six different administration schedules of RO4929097
Time frame: Up to 4 weeks
Determination of pharmacokinetic profiles of various administration schedules
Time frame: Up to 4 weeks
Preliminary antitumor activity of RO4929097 assessed using RECIST 1.1 criteria
Time frame: Up to 4 weeks
Pharmacokinetic (PK) parameters of RO4929097 administered using six different dosing schedules
Time frame: Up to 4 weeks
This study is completed, as verified in Dec 2013. You cannot join it, but the record below documents what was studied.
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National Cancer Institute (NCI)