Trial Outcomes & Findings for LDE225 for Patients With PTCH1 or SMO Mutated Tumors (NCT NCT02002689)
NCT ID: NCT02002689
Last Updated: 2016-05-02
Results Overview
Clinical benefit rate (CBR) Number and percentage of subjects with CBR (responses of CR, PR or SD ≥ 16 weeks) as assessed by investigator was reported for all patients along with 95% exact confidence interval (CI). Overall Response Rate (ORR) Overall response was to be determined by investigator assessment for each tumor in the study. For subjects with solid tumors, the assessment criteria was RECIST 1.1 and included responses of CR and/or PR. The number and percentage of subjects for different categories of overall response (e.g., for solid tumors - CR, PR, SD, PD, Not Evaluable) were to be provided for solid tumors, and each hematological tumor type (if applicable). Ninety-five percent (95%) exact CI was to be provided for the response rate(s) (e.g., for solid tumors - CRn and/or PR) as well.
TERMINATED
PHASE2
10 participants
16 weeks
2016-05-02
Participant Flow
The study was closed for accrual when the sponsor realized that not enough patients will be recruited for any meaningful stat analysis even if the study were kept open beyond the original planned accrual window.
Participant milestones
| Measure |
Sonidegib
All the patients received sonidegib on a flat scale of 800 mg (e.g., 4 x 200 mg hard gelatin capsules) once daily on a continuous dosing cycle.
|
|---|---|
|
Overall Study
STARTED
|
10
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
10
|
Reasons for withdrawal
| Measure |
Sonidegib
All the patients received sonidegib on a flat scale of 800 mg (e.g., 4 x 200 mg hard gelatin capsules) once daily on a continuous dosing cycle.
|
|---|---|
|
Overall Study
Disease Progression
|
7
|
|
Overall Study
Adverse Event
|
3
|
Baseline Characteristics
LDE225 for Patients With PTCH1 or SMO Mutated Tumors
Baseline characteristics by cohort
| Measure |
Sonidegib
n=10 Participants
All the patients received sonidegib on a flat scale of 800 mg (e.g., 4 x 200 mg hard gelatin capsules) once daily on a continuous dosing cycle.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
4 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
6 Participants
n=5 Participants
|
|
Age, Continuous
|
63.2 years
STANDARD_DEVIATION 7.64 • n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 16 weeksPopulation: Full analysis set
Clinical benefit rate (CBR) Number and percentage of subjects with CBR (responses of CR, PR or SD ≥ 16 weeks) as assessed by investigator was reported for all patients along with 95% exact confidence interval (CI). Overall Response Rate (ORR) Overall response was to be determined by investigator assessment for each tumor in the study. For subjects with solid tumors, the assessment criteria was RECIST 1.1 and included responses of CR and/or PR. The number and percentage of subjects for different categories of overall response (e.g., for solid tumors - CR, PR, SD, PD, Not Evaluable) were to be provided for solid tumors, and each hematological tumor type (if applicable). Ninety-five percent (95%) exact CI was to be provided for the response rate(s) (e.g., for solid tumors - CRn and/or PR) as well.
Outcome measures
| Measure |
Sonidegib
n=10 Participants
All the patients received sonidegib on a flat scale of 800 mg (e.g., 4 x 200 mg hard gelatin capsules) once daily on a continuous dosing cycle.
|
|---|---|
|
Summary of Overall Response (ORR) and Clinical Benefit (CBR)
Complete response (CR)
|
0 percent responders
|
|
Summary of Overall Response (ORR) and Clinical Benefit (CBR)
Partial response (PR)
|
0 percent responders
|
|
Summary of Overall Response (ORR) and Clinical Benefit (CBR)
Stable disease (SD)
|
0 percent responders
|
|
Summary of Overall Response (ORR) and Clinical Benefit (CBR)
Progressive disease (PD)
|
8 percent responders
|
|
Summary of Overall Response (ORR) and Clinical Benefit (CBR)
Non-evaluable (NE)
|
2 percent responders
|
|
Summary of Overall Response (ORR) and Clinical Benefit (CBR)
Overall response rate (ORR: CR+PR)
|
0 percent responders
|
|
Summary of Overall Response (ORR) and Clinical Benefit (CBR)
Clinical benefit rate (CBR: CR+PR+SD)
|
0 percent responders
|
SECONDARY outcome
Timeframe: 4 monthsPopulation: Full Analysis set
Progression-free survival (PFS) is the time from the date of start of treatment to the date of event defined as the first documented progression or death due to any cause within 30 days of last dose. If a subject has not had an event, progression-free survival is censored at the date of last adequate tumor assessment.
Outcome measures
| Measure |
Sonidegib
n=10 Participants
All the patients received sonidegib on a flat scale of 800 mg (e.g., 4 x 200 mg hard gelatin capsules) once daily on a continuous dosing cycle.
|
|---|---|
|
Summary of Timing and Estimated Rate for Progression-free Survival (PFS) - Full Analysis Set
1 Month
|
88.9 % progression free surviors
Interval 43.3 to 98.4
|
|
Summary of Timing and Estimated Rate for Progression-free Survival (PFS) - Full Analysis Set
2 Months
|
33.3 % progression free surviors
Interval 7.8 to 62.3
|
|
Summary of Timing and Estimated Rate for Progression-free Survival (PFS) - Full Analysis Set
3 Months
|
33.3 % progression free surviors
Interval 7.8 to 62.3
|
|
Summary of Timing and Estimated Rate for Progression-free Survival (PFS) - Full Analysis Set
4 Months
|
0.0 % progression free surviors
limits not needed for 0 observations
|
SECONDARY outcome
Timeframe: 4 monthsOutcome measures
| Measure |
Sonidegib
n=10 Participants
All the patients received sonidegib on a flat scale of 800 mg (e.g., 4 x 200 mg hard gelatin capsules) once daily on a continuous dosing cycle.
|
|---|---|
|
Kaplan-Meier Estimates of Progression Free Survival (PFS )Timing, Months
|
1.8 months
Interval 0.9 to 3.6
|
Adverse Events
LDE225
Serious adverse events
| Measure |
LDE225
n=10 participants at risk
All the patients received sonidegib on a flat scale of 800 mg (e.g., 4 x 200 mg hard gelatin capsules) once daily on a continuous dosing cycle.
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
20.0%
2/10
|
|
Gastrointestinal disorders
Dysphagia
|
10.0%
1/10
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
10.0%
1/10
|
|
Infections and infestations
Pneumonia
|
10.0%
1/10
|
|
Metabolism and nutrition disorders
Dehydration
|
20.0%
2/10
|
|
Metabolism and nutrition disorders
Failure to thrive
|
10.0%
1/10
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
10.0%
1/10
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
10.0%
1/10
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
10.0%
1/10
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
10.0%
1/10
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
10.0%
1/10
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
10.0%
1/10
|
Other adverse events
| Measure |
LDE225
n=10 participants at risk
All the patients received sonidegib on a flat scale of 800 mg (e.g., 4 x 200 mg hard gelatin capsules) once daily on a continuous dosing cycle.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
10.0%
1/10
|
|
Gastrointestinal disorders
Abdominal pain
|
20.0%
2/10
|
|
Gastrointestinal disorders
Constipation
|
30.0%
3/10
|
|
Gastrointestinal disorders
Diarrhoea
|
30.0%
3/10
|
|
Gastrointestinal disorders
Dyspepsia
|
10.0%
1/10
|
|
Gastrointestinal disorders
Dysphagia
|
10.0%
1/10
|
|
Gastrointestinal disorders
Nausea
|
80.0%
8/10
|
|
Gastrointestinal disorders
Vomiting
|
40.0%
4/10
|
|
General disorders
Asthenia
|
20.0%
2/10
|
|
General disorders
Fatigue
|
60.0%
6/10
|
|
General disorders
Oedema peripheral
|
10.0%
1/10
|
|
General disorders
Pain
|
10.0%
1/10
|
|
Infections and infestations
Urinary tract infection
|
30.0%
3/10
|
|
Investigations
Activated partial thromboplastin time prolonged
|
10.0%
1/10
|
|
Investigations
Alanine aminotransferase increased
|
30.0%
3/10
|
|
Investigations
Aspartate aminotransferase increased
|
30.0%
3/10
|
|
Investigations
Blood alkaline phosphatase increased
|
20.0%
2/10
|
|
Investigations
Blood creatine phosphokinase increased
|
30.0%
3/10
|
|
Investigations
Blood lactate dehydrogenase increased
|
10.0%
1/10
|
|
Investigations
Blood uric acid increased
|
10.0%
1/10
|
|
Investigations
Gamma-glutamyltransferase increased
|
30.0%
3/10
|
|
Investigations
Haemoglobin decreased
|
10.0%
1/10
|
|
Investigations
Weight decreased
|
40.0%
4/10
|
|
Investigations
White blood cell count decreased
|
10.0%
1/10
|
|
Metabolism and nutrition disorders
Decreased appetite
|
50.0%
5/10
|
|
Metabolism and nutrition disorders
Dehydration
|
10.0%
1/10
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
10.0%
1/10
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
20.0%
2/10
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
10.0%
1/10
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
10.0%
1/10
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
10.0%
1/10
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
10.0%
1/10
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
10.0%
1/10
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
20.0%
2/10
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
10.0%
1/10
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
10.0%
1/10
|
|
Nervous system disorders
Dysgeusia
|
20.0%
2/10
|
|
Nervous system disorders
Headache
|
10.0%
1/10
|
|
Nervous system disorders
Neuropathy peripheral
|
10.0%
1/10
|
|
Psychiatric disorders
Depression
|
10.0%
1/10
|
|
Psychiatric disorders
Irritability
|
10.0%
1/10
|
|
Renal and urinary disorders
Proteinuria
|
30.0%
3/10
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
30.0%
3/10
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
10.0%
1/10
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
10.0%
1/10
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
20.0%
2/10
|
Additional Information
Clinical Disclosure Office
Novartis Pharmaceuticals
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
- Publication restrictions are in place
Restriction type: OTHER