This phase II trial is studying the side effects and how well RO4929097 works in treating patients with recurrent and/or metastatic epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer. RO4929097 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVES: I. To assess the antitumor activity of RO4929097 in recurrent and / or metastatic epithelial ovarian cancer, fallopian tube cancer and primary peritoneal cancer by progression free survival rate at the end of 4 cycles. SECONDARY OBJECTIVES: I. To assess the antitumor activity of RO4929097 through secondary endpoints including: overall response rate and CA125 response rate (GCIC criteria). II. To assess the safety of single agent RO4929097 in advanced platinum resistant ovarian, fallopian tube and primary peritoneal cancers. III. To explore expression of Notch biomarkers in advanced platinum resistant ovarian, fallopian, and primary peritoneal cancers. IV. To explore the impact of RO49097 on ascitic fluid circulating tumor cells. OUTLINE: This is a multicenter study. Patients receive oral gamma-secretase inhibitor RO4929097 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. Blood and tumor tissue samples are collected for correlative studies. Ascitic fluid may also be collected. After completion of study therapy, patients are followed up every month for at least 1 year.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
45
Given PO
Correlative studies
Tower Cancer Research Foundation
Beverly Hills, California, United States
City of Hope Comprehensive Cancer Center
Duarte, California, United States
Los Angeles County-USC Medical Center
Los Angeles, California, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, United States
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton, Ontario, Canada
Cancer Centre of Southeastern Ontario at Kingston General Hospital
Kingston, Ontario, Canada
London Regional Cancer Program
London, Ontario, Canada
Credit Valley Hospital
Mississauga, Ontario, Canada
...and 2 more locations
Four Cycle Progression-free Survival Rate
Defined as the proportion of the study population that has not had tumor progression (symptomatic, RECIST progression, CA-125 progression) or died at the completion of the cycle four mark. RECIST criteria for progressive disease (PD) in target lesions: \>= 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. The appearance of one or more new lesions is also considered progression. In non-target lesions: Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. CA-125 PD is based on the progressive serial elevation of serum CA-125 according to: A) elevated CA-125 pretreatment \& normalization of CA-125 or C) CA-125 in normal range pretreatment: CA-125 \>= 2x ULN on 2 occasions. B) elevated CA-125 pretreatment that never normalizes: CA-125 \>= 2x nadir value on 2 occasions
Time frame: 84 days (4 courses)
Overall Response Rate
Response was assessed by Response Evaluation Criteria In Solid Tumors (RECIST 1.1). Evaluation of Target Lesions: Complete response (CR) - disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response (PR) - at least 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Evaluation of Non-Target Lesions: Complete response (CR) - disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis).
Time frame: Time from start of treatment to time of disease progression or death from any cause, whichever came first, assessed up to 2 years
CA125 Response Rate (GCIG Criteria)
The CA-125 response rate is defined as the proportion of patients with a Gynecological Cancer Intergroup (GCIG) CA-125 response. CA-125 response is defined as the moment CA-125 is reduced by 50% from the last pre-treatment level prior to start of therapy. The response must be confirmed and maintained with a consecutive CA-125 for at least 28 days.
Time frame: Time from start of treatment to time of disease progression or death from any cause, whichever came first, assessed up to 2 years
Overall Survival
Summary statistics, such as mean, median, counts and proportion, used to summarize the patients. Survival estimates computed using Kaplan-Meier method. Potential association between variables measured using Pearson correlation coefficients, chi-square tests, one- or two-sample t-tests or logistic regression analyses as appropriate. Non-parametric tests such as Spearman correlation coefficients, Fisher's exact tests and Wilcoxon rank sum tests may be substituted if necessary. Ninety-five percent confidence intervals will be constructed and selected results illustrated using figures and plots.
Time frame: Up to 2 years
Frequency and Severity of Adverse Events
Tabulated using counts and proportions detailing frequently occurring, serious and severe events of interest.
Time frame: Up to 2 years
Expression of Notch Biomarkers in Advanced Platinum Resistant Ovarian, Fallopian, and Primary Peritoneal Cancers.
An exploratory analysis for potential predictive biomarkers was performed on archival, paraffin-embedded tumor tissue for components of the Notch Pathway: Jagged-1 and NICD. The percentage of positive cells were scored into four categories: 0 (0%), 1 (1-33%), 2 (34-66%), and 3 (67-100%). The product of the intensity and percentage scores was used as the final score and classified as negative (0-4) or positive (5-9).
Time frame: Up to 2 years
Impact of RO49097 on Ascitic Fluid Circulating Tumor Cells
Impact of RO49097 on ascitic fluid circulating tumor cells.
Time frame: Up to 2 years
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