Trial Outcomes & Findings for RO4929097 in Treating Patients With Advanced Non-Small Cell Lung Cancer Who Have Recently Completed Treatment With Front-Line Chemotherapy (NCT NCT01193868)
NCT ID: NCT01193868
Last Updated: 2015-11-18
Results Overview
Percentage of participants with response per RECIST version 1.1: Complete Response (CR):Disappearance all target lesions. Any pathological lymph nodes with reduction in short axis to \<10 mm. Partial Response (PR): At least 30% decrease in sum of diameters of target lesions, reference baseline sum diameters. Progressive Disease (PD): At least 20% increase in sum of diameters of target lesions, reference smallest sum on study (includes baseline sum if that is smallest on study). In addition to relative increase of 20%, sum must demonstrate an absolute increase of at least 5 mm. (Note: appearance of 1 or more new lesions also considered progressions). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, reference smallest sum diameters while on study. Best response recorded from treatment start until disease progression/recurrence (reference for progressive disease the smallest measurements recorded since treatment started).
TERMINATED
PHASE2
6 participants
Response evaluation every 6 weeks (in addition to baseline scan, confirmatory scans approximately 6-7 (not less than 4) weeks following initial documentation of objective response). Expected follow up to 5 years, actual study period 9/2010 to 4/2014.
2015-11-18
Participant Flow
Recruitment Period: September 15, 2010 to June 29, 2012. Recruitment done at The University of Texas MD Anderson Cancer Center.
Study terminated early as a result of discontinued production of the study drug.
Participant milestones
| Measure |
RO4929097
Oral gamma-secretase inhibitor RO4929097 once daily on days 1-3, 8-10, and 15-17. Courses repeat every 21 days
|
|---|---|
|
Overall Study
STARTED
|
6
|
|
Overall Study
COMPLETED
|
6
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
RO4929097 in Treating Patients With Advanced Non-Small Cell Lung Cancer Who Have Recently Completed Treatment With Front-Line Chemotherapy
Baseline characteristics by cohort
| Measure |
RO4929097
n=6 Participants
Oral gamma-secretase inhibitor RO4929097 once daily on days 1-3, 8-10, and 15-17. Courses repeat every 21 days
|
|---|---|
|
Age, Continuous
|
65 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
5 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
6 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Response evaluation every 6 weeks (in addition to baseline scan, confirmatory scans approximately 6-7 (not less than 4) weeks following initial documentation of objective response). Expected follow up to 5 years, actual study period 9/2010 to 4/2014.Population: Only those participants who have measurable disease present at baseline and received at least one dose of study medication considered evaluable for response with their response classified according to the RECIST definitions stated. Participants who exhibit objective disease progression prior to the end of cycle 1 also considered evaluable.
Percentage of participants with response per RECIST version 1.1: Complete Response (CR):Disappearance all target lesions. Any pathological lymph nodes with reduction in short axis to \<10 mm. Partial Response (PR): At least 30% decrease in sum of diameters of target lesions, reference baseline sum diameters. Progressive Disease (PD): At least 20% increase in sum of diameters of target lesions, reference smallest sum on study (includes baseline sum if that is smallest on study). In addition to relative increase of 20%, sum must demonstrate an absolute increase of at least 5 mm. (Note: appearance of 1 or more new lesions also considered progressions). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, reference smallest sum diameters while on study. Best response recorded from treatment start until disease progression/recurrence (reference for progressive disease the smallest measurements recorded since treatment started).
Outcome measures
| Measure |
RO4929097
n=5 Participants
Oral gamma-secretase inhibitor RO4929097 once daily on days 1-3, 8-10, and 15-17. Courses repeat every 21 days
|
|---|---|
|
Response Rate by Response Evaluation Criteria in Solid Tumors (RECIST)
Partial Response (PR)
|
0 percentage of participants
|
|
Response Rate by Response Evaluation Criteria in Solid Tumors (RECIST)
Complete Response (CR)
|
0 percentage of participants
|
|
Response Rate by Response Evaluation Criteria in Solid Tumors (RECIST)
Progression (PD)
|
100 percentage of participants
|
|
Response Rate by Response Evaluation Criteria in Solid Tumors (RECIST)
Stable Disease (SD)
|
0 percentage of participants
|
PRIMARY outcome
Timeframe: 6 weeksPopulation: Study terminated early with low accrual leading to insufficient data for analysis.
Response is reported as a continuous variable, as % change in tumor size from baseline. Pearson and Spearman correlation coefficients will be used. Reported with 95% two-sided confidence intervals.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to day 3Population: Study terminated early with low accrual leading to insufficient data for analysis.
For participants having biopsies both before and after the agent, paired comparisons of post-therapy to pre-therapy results for the Notch IHC scores will be used. Researchers will assess changes from pre-therapy to post-therapy using a Wilcoxon Signed Rank Test (Wilcoxon rank sum tests). Spearman coefficients will be used to correlate tumor expression of Notch pathway markers with expression of stem cell markers.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to day 3Population: Study terminated early with low accrual leading to insufficient data for analysis.
Wilcoxon rank sum tests will be used. For participants having biopsies both before and after the agent, paired comparisons of post-therapy to pre-therapy results for the Notch IHC scores will be used. Researchers will assess changes from pre-therapy to post-therapy using a Wilcoxon Signed Rank Test (Wilcoxon rank sum tests).
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to day 3Population: Study terminated early with low accrual leading to insufficient data for analysis.
Wilcoxon rank sum tests will be used. Compared using Fisher Exact Tests. For participants having biopsies both before and after the agent, paired comparisons of post-therapy to pre-therapy results for the Notch IHC scores will be used. Researchers will assess changes from pre-therapy to post-therapy using a Wilcoxon Signed Rank Test (Sum Test). Spearman coefficients will be used to correlate tumor expression of Notch pathway markers with expression of stem cell markers.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to day 3Population: Study terminated early. Analysis not performed due to small numbers.
Wilcoxon rank sum tests will be used.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 3 monthsPopulation: Study terminated early with low accrual leading to insufficient data for analysis.
Tumor Immunohistochemistry (IHC) scores for Notch pathway and stem cell markers used in comparison to tumor progression; and progression evaluated in using international criteria proposed by revised RECIST guideline (version 1.1). Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria. Wilcoxon rank sum tests will be used. Compared using Fisher Exact Tests.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 6 weeksPopulation: Study terminated early. Analysis not performed due to small numbers.
Correlate percent change in tumor size at 6 weeks (or at time off study, if therapy is stopped earlier due to tumor progression) with tumor Immunohistochemistry (IHC) scores for Notch pathway and stem cell markers; Tumor % shrinkage with RO4929097 will correlate with pre-therapy tumor expression of Notch pathway members, with expression of stem cell markers, and with changes in these over the first cycle of therapy.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline up to 5 yearsPopulation: Study terminated early. Analysis not performed due to small numbers.
Time from initiation of study drug until death, progression of tumor, or for worsening of tumor that did not meet RECIST 1.1 criteria but that did require discontinuation of therapy, assessed up to 5 years
Outcome measures
Outcome data not reported
Adverse Events
RO4929097
Serious adverse events
| Measure |
RO4929097
n=6 participants at risk
Oral gamma-secretase inhibitor RO4929097 once daily on days 1-3, 8-10, and 15-17. Courses repeat every 21 days
|
|---|---|
|
General disorders
Death NOS
|
33.3%
2/6 • Number of events 2 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Cardiac disorders
Cardiac arrest
|
16.7%
1/6 • Number of events 1 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Disease progression
|
16.7%
1/6 • Number of events 1 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
Other adverse events
| Measure |
RO4929097
n=6 participants at risk
Oral gamma-secretase inhibitor RO4929097 once daily on days 1-3, 8-10, and 15-17. Courses repeat every 21 days
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
16.7%
1/6 • Number of events 1 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Investigations
Activated partial thromboplastin time prolonged
|
16.7%
1/6 • Number of events 1 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Investigations
Alkaline phosphatase increased
|
50.0%
3/6 • Number of events 3 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis
|
16.7%
1/6 • Number of events 1 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
16.7%
1/6 • Number of events 1 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Blood and lymphatic system disorders
Anemia
|
100.0%
6/6 • Number of events 9 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Metabolism and nutrition disorders
Anorexia
|
33.3%
2/6 • Number of events 2 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Psychiatric disorders
Anxiety
|
33.3%
2/6 • Number of events 2 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Investigations
Aspartate aminotransferase increased
|
16.7%
1/6 • Number of events 2 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Respiratory, thoracic and mediastinal disorders
Aspiration
|
16.7%
1/6 • Number of events 1 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Respiratory, thoracic and mediastinal disorders
Atelectasis
|
16.7%
1/6 • Number of events 1 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
83.3%
5/6 • Number of events 5 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Investigations
Blood bilirubin increased
|
16.7%
1/6 • Number of events 1 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
16.7%
1/6 • Number of events 1 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Respiratory, thoracic and mediastinal disorders
Bronchial obstruction
|
16.7%
1/6 • Number of events 1 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Investigations
Cholesterol high
|
16.7%
1/6 • Number of events 1 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Gastrointestinal disorders
Constipation
|
33.3%
2/6 • Number of events 3 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Metabolism and nutrition disorders
Dehydration
|
16.7%
1/6 • Number of events 1 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Psychiatric disorders
Depression
|
16.7%
1/6 • Number of events 1 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Nervous system disorders
Dizziness
|
16.7%
1/6 • Number of events 1 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Nervous system disorders
Dysgeusia
|
16.7%
1/6 • Number of events 1 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Gastrointestinal disorders
Dyspepsia
|
16.7%
1/6 • Number of events 1 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
66.7%
4/6 • Number of events 5 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
General disorders
Edema limbs
|
16.7%
1/6 • Number of events 1 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
General disorders
Fatigue
|
83.3%
5/6 • Number of events 6 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
16.7%
1/6 • Number of events 1 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Metabolism and nutrition disorders
Glucose intolerance
|
16.7%
1/6 • Number of events 1 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Ear and labyrinth disorders
Hearing impaired
|
16.7%
1/6 • Number of events 1 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
16.7%
1/6 • Number of events 1 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
16.7%
1/6 • Number of events 1 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
33.3%
2/6 • Number of events 2 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
16.7%
1/6 • Number of events 1 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
16.7%
1/6 • Number of events 1 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Metabolism and nutrition disorders
Hypokalemia
|
16.7%
1/6 • Number of events 1 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
50.0%
3/6 • Number of events 3 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Metabolism and nutrition disorders
Hyponatremia
|
66.7%
4/6 • Number of events 5 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Vascular disorders
Hypotension
|
16.7%
1/6 • Number of events 1 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Infections and infestations
Lung infection
|
16.7%
1/6 • Number of events 1 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Gastrointestinal disorders
Mucositis oral
|
16.7%
1/6 • Number of events 1 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
16.7%
1/6 • Number of events 1 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Gastrointestinal disorders
Nausea
|
66.7%
4/6 • Number of events 5 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
General disorders
Pain
|
33.3%
2/6 • Number of events 3 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
33.3%
2/6 • Number of events 2 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Reproductive system and breast disorders
Pelvic pain
|
16.7%
1/6 • Number of events 1 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Investigations
Platelet count decreased
|
16.7%
1/6 • Number of events 1 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
16.7%
1/6 • Number of events 1 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
16.7%
1/6 • Number of events 1 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
16.7%
1/6 • Number of events 1 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Infections and infestations
Sepsis
|
16.7%
1/6 • Number of events 1 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Cardiac disorders
Sinus tachycardia
|
16.7%
1/6 • Number of events 1 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Vascular disorders
Thromboembolic event
|
16.7%
1/6 • Number of events 1 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Nervous system disorders
Tremor
|
16.7%
1/6 • Number of events 1 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Renal and urinary disorders
Urinary incontinence
|
16.7%
1/6 • Number of events 1 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Gastrointestinal disorders
Vomiting
|
16.7%
1/6 • Number of events 1 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
16.7%
1/6 • Number of events 1 • Adverse events reporting includes events that occur within 30 days of the last dose of the investigational agent/treatment. Overall study period: 9/15/2010 to 6/20/2013.
|
Additional Information
George Blumenschein, MD / Professor
The University of Texas MD Anderson Cancer Center
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60