Gamma-Secretase Inhibitor RO4929097 and Cediranib Maleate in Treating Patients With Advanced Solid Tumors
|ClinicalTrials.gov Identifier: NCT01131234|
Recruitment Status : Completed
First Posted : May 26, 2010
Last Update Posted : December 23, 2014
|Condition or disease||Intervention/treatment||Phase|
|Adult Anaplastic Astrocytoma Adult Anaplastic Ependymoma Adult Anaplastic Oligodendroglioma Adult Brain Stem Glioma Adult Giant Cell Glioblastoma Adult Glioblastoma Adult Gliosarcoma Adult Mixed Glioma Adult Solid Neoplasm Male Breast Carcinoma Recurrent Adult Brain Neoplasm Recurrent Breast Carcinoma Recurrent Colon Carcinoma Recurrent Melanoma 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||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1, Pharmacokinetic and Pharmacodynamic Study of the Combination of RO4929097 and Cediranib in Patients With Advanced Solid Tumors|
|Study Start Date :||May 2010|
|Actual Primary Completion Date :||September 2014|
|Actual Study Completion Date :||September 2014|
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
- 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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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|