Trial Outcomes & Findings for RO4929097 in Treating Patients With Recurrent and/or Metastatic Epithelial Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer (NCT NCT01175343)

Last Updated: 2017-05-24

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

45 participants

Primary outcome timeframe

84 days (4 courses)

Results posted on

2017-05-24

Participant Flow

One patient was taken off study prior to start of study drug for meeting exclusion criteria 3.2.5 (i.e. patient is taking concurrent medications that are strong inducers, inhibitors or substrates of CYP3A4 who cannot be switched to alternative medications).

Participant milestones

Participant milestones
Measure	Treatment (RO4929097) 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. Gamma-Secretase Inhibitor RO4929097: Given PO Laboratory Biomarker Analysis: Correlative studies
Overall Study STARTED	44
Overall Study COMPLETED	44
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

RO4929097 in Treating Patients With Recurrent and/or Metastatic Epithelial Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (RO4929097) n=45 Participants 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. Gamma-Secretase Inhibitor RO4929097: Given PO Laboratory Biomarker Analysis: Correlative studies
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	34 Participants n=5 Participants
Age, Categorical >=65 years	11 Participants n=5 Participants
Age, Continuous	58 years n=5 Participants
Sex: Female, Male Female	45 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 84 days (4 courses)

Outcome measures

Outcome measures
Measure	Treatment (RO4929097) n=44 Participants 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. Gamma-Secretase Inhibitor RO4929097: Given PO Laboratory Biomarker Analysis: Correlative studies
Four Cycle Progression-free Survival Rate	8 Participants

SECONDARY outcome

Timeframe: Time from start of treatment to time of disease progression or death from any cause, whichever came first, assessed up to 2 years

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).

Outcome measures

Outcome measures
Measure	Treatment (RO4929097) n=44 Participants 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. Gamma-Secretase Inhibitor RO4929097: Given PO Laboratory Biomarker Analysis: Correlative studies
Overall Response Rate	0 Participants

SECONDARY outcome

Timeframe: Time from start of treatment to time of disease progression or death from any cause, whichever came first, assessed up to 2 years

Population: There are 40 patients evaluable for response.

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.

Outcome measures

Outcome measures
Measure	Treatment (RO4929097) n=40 Participants 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. Gamma-Secretase Inhibitor RO4929097: Given PO Laboratory Biomarker Analysis: Correlative studies
CA125 Response Rate (GCIG Criteria)	1 Participants

SECONDARY outcome

Timeframe: Up to 2 years

Population: 40 patients are evaluable for response.

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.

Outcome measures

Outcome measures
Measure	Treatment (RO4929097) n=40 Participants 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. Gamma-Secretase Inhibitor RO4929097: Given PO Laboratory Biomarker Analysis: Correlative studies
Overall Survival	NA months Not reached

SECONDARY outcome

Timeframe: Up to 2 years

Population: Adverse events analyzed include all serious adverse events (SAEs), and other (non-serious) treatment-related adverse events.There are 21 SAEs and 72 other (non-serious) adverse events.

Tabulated using counts and proportions detailing frequently occurring, serious and severe events of interest.

Outcome measures

Outcome measures
Measure	Treatment (RO4929097) n=93 Adverse Events 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. Gamma-Secretase Inhibitor RO4929097: Given PO Laboratory Biomarker Analysis: Correlative studies
Frequency and Severity of Adverse Events All Adverse Events · Grade 1/2	71 Adverse Events
Frequency and Severity of Adverse Events All Adverse Events · Grade 3/4	22 Adverse Events
Frequency and Severity of Adverse Events Serious Adverse Events · Grade 1/2	2 Adverse Events
Frequency and Severity of Adverse Events Serious Adverse Events · Grade 3/4	19 Adverse Events
Frequency and Severity of Adverse Events Other Adverse Events · Grade 1/2	69 Adverse Events
Frequency and Severity of Adverse Events Other Adverse Events · Grade 3/4	3 Adverse Events

SECONDARY outcome

Timeframe: Up to 2 years

Population: 25 patients were assessed for Jagged-1 expression. 17 patients that were evaluable for response were assessed for NICD expression.

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).

Outcome measures

Outcome measures
Measure	Treatment (RO4929097) n=25 Participants 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. Gamma-Secretase Inhibitor RO4929097: Given PO Laboratory Biomarker Analysis: Correlative studies
Expression of Notch Biomarkers in Advanced Platinum Resistant Ovarian, Fallopian, and Primary Peritoneal Cancers. Jagged-1 expression · Positive	23 Participants
Expression of Notch Biomarkers in Advanced Platinum Resistant Ovarian, Fallopian, and Primary Peritoneal Cancers. Jagged-1 expression · Negative	2 Participants
Expression of Notch Biomarkers in Advanced Platinum Resistant Ovarian, Fallopian, and Primary Peritoneal Cancers. NICD expression · Positive	6 Participants
Expression of Notch Biomarkers in Advanced Platinum Resistant Ovarian, Fallopian, and Primary Peritoneal Cancers. NICD expression · Negative	11 Participants

SECONDARY outcome

Timeframe: Up to 2 years

Population: Data were not collected.

Impact of RO49097 on ascitic fluid circulating tumor cells.

Outcome measures

Outcome data not reported

Adverse Events

Treatment (RO4929097)

Serious events: 10 serious events

Other events: 44 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (RO4929097) n=44 participants at risk 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. Gamma-Secretase Inhibitor RO4929097: Given PO Laboratory Biomarker Analysis: Correlative studies
Cardiac disorders Pericardial effusion	2.3% 1/44 • Number of events 1
Gastrointestinal disorders Abdominal pain	2.3% 1/44 • Number of events 1
Gastrointestinal disorders Ascites	2.3% 1/44 • Number of events 1
Gastrointestinal disorders Diarrhea	2.3% 1/44 • Number of events 1
Gastrointestinal disorders Small intestinal obstruction	6.8% 3/44 • Number of events 3
Gastrointestinal disorders Vomiting	4.5% 2/44 • Number of events 2
Investigations Aspartate aminotransferase increased	2.3% 1/44 • Number of events 1
Investigations Blood bilirubin increased	2.3% 1/44 • Number of events 1
Investigations GGT increased	2.3% 1/44 • Number of events 1
Metabolism and nutrition disorders Dehydration	2.3% 1/44 • Number of events 1
Musculoskeletal and connective tissue disorders Back pain	2.3% 1/44 • Number of events 1
Musculoskeletal and connective tissue disorders Muscle weakness upper limb	2.3% 1/44 • Number of events 1
Nervous system disorders Intracranial hemorrhage	2.3% 1/44 • Number of events 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Parietal mass	2.3% 1/44 • Number of events 1
Reproductive system and breast disorders Vaginal hemorrhage	2.3% 1/44 • Number of events 1
Respiratory, thoracic and mediastinal disorders Dyspnea	4.5% 2/44 • Number of events 2
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.3% 1/44 • Number of events 1

Other adverse events

Other adverse events
Measure	Treatment (RO4929097) n=44 participants at risk 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. Gamma-Secretase Inhibitor RO4929097: Given PO Laboratory Biomarker Analysis: Correlative studies
Gastrointestinal disorders Nausea	34.1% 15/44
General disorders Fatigue	27.3% 12/44
Metabolism and nutrition disorders Hypophosphatemia	15.9% 7/44
Metabolism and nutrition disorders Anorexia	13.6% 6/44
Blood and lymphatic system disorders Anemia	11.4% 5/44
Nervous system disorders Headache	11.4% 5/44
Gastrointestinal disorders Vomiting	11.4% 5/44
Investigations ALT increase	11.4% 5/44
Investigations AST increase	6.8% 3/44
Gastrointestinal disorders Diarrhea	6.8% 3/44
Investigations Transient QT interval prolongation	13.6% 6/44

Additional Information

Dr. Amit M. Oza

Princess Margaret Cancer Centre

Phone: 416-946-2818

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60