Gamma-Secretase Inhibitor RO4929097 and Cediranib Maleate in Treating Patients With Advanced Solid Tumors
Adult Anaplastic Astrocytoma
Adult Anaplastic Ependymoma
Adult Anaplastic Oligodendroglioma
Adult Brain Stem Glioma
Adult Giant Cell Glioblastoma
Adult Mixed Glioma
Adult Solid Neoplasm
Male Breast Carcinoma
Recurrent Adult Brain Neoplasm
Recurrent Breast Carcinoma
Recurrent Colon Carcinoma
Recurrent Non-Small Cell Lung Carcinoma
Recurrent Ovarian Carcinoma
Recurrent Ovarian Germ Cell Tumor
Recurrent Pancreatic Carcinoma
Recurrent Rectal Carcinoma
Recurrent Renal Cell Carcinoma
Stage III Pancreatic Cancer
Stage III Renal Cell Cancer
Stage IIIA Colon Cancer
Stage IIIA Non-Small Cell Lung Cancer
Stage IIIA Ovarian Cancer
Stage IIIA Ovarian Germ Cell Tumor
Stage IIIA Rectal Cancer
Stage IIIA Skin Melanoma
Stage IIIB Breast Cancer
Stage IIIB Colon Cancer
Stage IIIB Non-Small Cell Lung Cancer
Stage IIIB Ovarian Cancer
Stage IIIB Ovarian Germ Cell Tumor
Stage IIIB Rectal Cancer
Stage IIIB Skin Melanoma
Stage IIIC Breast Cancer
Stage IIIC Colon Cancer
Stage IIIC Ovarian Cancer
Stage IIIC Ovarian Germ Cell Tumor
Stage IIIC Rectal Cancer
Stage IIIC Skin Melanoma
Stage IV Breast Cancer
Stage IV Non-Small Cell Lung Cancer
Stage IV Ovarian Cancer
Stage IV Ovarian Germ Cell Tumor
Stage IV Pancreatic Cancer
Stage IV Renal Cell Cancer
Stage IV Skin Melanoma
Stage IVA Colon Cancer
Stage IVA Rectal Cancer
Stage IVB Colon Cancer
Stage IVB Rectal Cancer
Drug: Gamma-Secretase Inhibitor RO4929097
Drug: Cediranib Maleate
Other: Pharmacological Study
Other: Laboratory Biomarker Analysis
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1, Pharmacokinetic and Pharmacodynamic Study of the Combination of RO4929097 and Cediranib in Patients With Advanced Solid Tumors|
- Recommended phase II dose of gamma-secretase inhibitor RO4929097 defined as the dose level at which < 1/6 patients experience dose-limiting toxicity as graded by the National Cancer Institute (NCI) CTCAE version 4.0 [ Time Frame: 42 days ]Frequency and severity of adverse events will be tabulated using counts and proportions detailing frequently occurring, serious and severe events of interest.
- Incidence of adverse events as graded by the NCI CTCAE version 4.0 [ Time Frame: Up to 4 weeks post-treatment ]Frequency and severity of adverse events will be tabulated using counts and proportions detailing frequently occurring, serious and severe events of interest.
- PK profiles for both drugs [ Time Frame: On days 1, 10, 22, and 38 of course 1, and then on day 1 of courses 2-6 ]PK parameters will be calculated by non-compartmental methods.
- PD effects of gamma-secretase inhibitor RO4929097 when administered alone and in combined with cediranib maleate [ Time Frame: On days 1 and 22 of course 1 and on day 1 of course 2 ]Standard descriptive statistics, such as the mean, median, range and proportion, will be used to summarize the patient sample and to estimate parameters of interest. Ninety-five percent confidence intervals will be provided for estimates of interest where possible.
- Preliminary antitumor efficacy [ Time Frame: Up to 4 weeks post-treatment ]Summary statistics, such as the mean, median, counts and proportion, will be used to describe patients' clinical characteristics. Objective response to treatment will be assessed using the RECIST criteria 1.1.
|Study Start Date:||May 2010|
|Study Completion Date:||September 2014|
|Primary Completion Date:||September 2014 (Final data collection date for primary outcome measure)|
Experimental: Treatment (cediranib maleate and RO4929097)
Patients receive gamma-secretase inhibitor RO4929097 PO QD on days 1-3, 8-10, and 15-17 (days 1-3, 8-10, 15-17 22-24, 29-31, and 36-38 of course 1 only) and cediranib maleate PO QD on days 1-21 (days 22-42 course 1 only). Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity
Drug: Gamma-Secretase Inhibitor RO4929097
Other Name: RO4929097Drug: Cediranib Maleate
Other Names:Other: Pharmacological Study
Other Name: pharmacological studiesOther: Laboratory Biomarker Analysis
I. To determine the tolerability, maximum tolerated dose (equivalent to the recommended phase II dose), and safety profile of RO4929097 (gamma-secretase inhibitor RO4929097) in combination with cediranib (cediranib maleate) in patients with advanced malignancies.
I. To obtain pharmacokinetic (PK) profiles for RO4929097 when administered alone and for RO492907 and cediranib in combination, in order to evaluate for interactive effects in PK (if any) between these two agents.
II. To evaluate pharmacodynamic (PD) effects of RO492907 when administered alone and in combination, with the goal of identifying potential predictive and PD markers that need further exploration and validation in future trials.
III. To assess for preliminary antitumor efficacy of this drug combination, especially in breast cancer, malignant melanoma, colorectal cancer, pancreatic cancer, kidney cancer, high grade glioma, non-small-cell lung cancer, and ovarian cancer.
OUTLINE: This is a dose-escalation study.
Patients receive gamma-secretase inhibitor RO4929097 orally (PO) once daily (QD) on days 1-3, 8-10, and 15-17 (days 1-3, 8-10, 15-17 22-24, 29-31, and 36-38 of course 1) and cediranib maleate PO QD on days 1-21 (days 22-42 course 1 only). Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 4 weeks.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01131234
|Juravinski Cancer Centre at Hamilton Health Sciences|
|Hamilton, Ontario, Canada, L8V 5C2|
|University Health Network-Princess Margaret Hospital|
|Toronto, Ontario, Canada, M5G 2M9|
|Principal Investigator:||Sebastien Hotte||University Health Network-Princess Margaret Hospital|