This phase II clinical trial studies how well gamma-secretase/Notch signalling pathway inhibitor RO4929097 works in treating patients with advanced, metastatic, or recurrent triple negative invasive breast cancer. Gamma-secretase/Notch signalling pathway inhibitor RO4929097 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVES: I. To assess the antitumour activity of RO4929097 in recurrent and/or metastatic triple negative breast cancer through co-primary endpoints of overall response rate (ORR) using RECIST and 6-month progression-free survival rate (PFS). SECONDARY OBJECTIVES: I. To assess the antitumour activity of RO4929097 through secondary endpoints including: duration of radiologic response, progression-free and overall survival rates within the protocol defined follow-up period. II. To assess the safety and tolerability of single agent RO4929097 in breast cancer. III. To explore expression of Notch biomarkers in triple negative breast cancer and potential interaction with RO4929097 response and toxicity. IV. To evaluate the downstream effects of RO4929097 in advanced triple negative breast cancer. OUTLINE: Patients receive gamma-secretase/Notch signalling pathway inhibitor RO4929097 orally (PO) once daily on days 1-3, 8-10, and 15-17. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 30 days.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
6
Given orally
Correlative studies
BCCA-Vancouver Cancer Centre
Vancouver, British Columbia, Canada
University Health Network-Princess Margaret Hospital
Toronto, Ontario, Canada
Overall Response Rate Using RECIST
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the diameters of target lesions; Overall Response (OR) = CR + PR.
Time frame: From start of treatment until disease progression or removal from treatment.
Progression-free Survival
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the diameters of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Computed using the Kaplan-Meier method.
Time frame: Time from start of study treatment to the date of first progression or death from any cause, whichever occurs first, assessed at 6 months
Progression-free Survival
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the diameters of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Computed using the Kaplan-Meier method.
Time frame: Time from start of study treatment to the date of first progression or death from any cause, whichever occurs first, assessed at 3 months
Duration of Radiologic Response
The duration of radiologic response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented.
Time frame: From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented.
Overall Survival
Computed using the Kaplan-Meier method.
Time frame: Within the protocol defined follow-up period.
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