PTCH1 or SMO Activated Solid and Hematologic Tumors
Conditions
Keywords
Solid tumor malignancy,, hematologic malignancy,, mutation, translocations,, signature,, PTCH1,, SMO,, LDE225,, endometrial cancer,, colon cancer,, bladder,, NSCLC
Brief summary
The purpose of this signal seeking study is to determine whether treatment with LDE225 demonstrates sufficient efficacy in hedgehog pathway-mutated solid tumors and/or hematologic malignancies to warrant further study
Interventions
DRUGLDE225
LDE225 800 mg (hard gelatin capsules) will be administered orally once daily on a continuous dosing schedule
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient has confirmed diagnosis of a select solid tumor (except medulloblastoma, basal cell carcinoma and pancreatic adenocarcinoma) or hematological malignancy (except CML, ALL and AML). * Patient has pre-identified tumor with a PTCH1 or SMO mutation. * Patient has received at least one prior treatment for recurrent, metastatic and /or locally advanced disease and for whom no standard therapy options are anticipated to result in a durable remission. * Patient has progressive and measurable disease as per RECIST 1.1. or other appropriate hematological guidelines. * Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
Exclusion criteria
* Patients has received prior treatment with LDE225. * Patients has neuromuscular disorders associated with elevated CK (i.e. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy) or are on concomitant treatment with drugs that are recognized to cause rhabdomyolysis * Patients has primary CNS tumor or CNS tumor involvement * Patient has received chemotherapy or anticancer therapy ≤ 4 weeks prior to starting study drug
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Summary of Overall Response (ORR) and Clinical Benefit (CBR) | 16 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Summary of Timing and Estimated Rate for Progression-free Survival (PFS) - Full Analysis Set | 4 months | 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. |
| Kaplan-Meier Estimates of Progression Free Survival (PFS )Timing, Months | 4 months | — |
Countries
United States
Participant flow
Recruitment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 10 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Disease Progression | 7 |
Baseline characteristics
| Characteristic | Sonidegib |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 6 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Age, Continuous | 63.2 years STANDARD_DEVIATION 7.64 |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 10 / 10 |
| serious Total, serious adverse events | 7 / 10 |
Outcome results
Primary
Summary of Overall Response (ORR) and Clinical Benefit (CBR)
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.
Time frame: 16 weeks
Population: Full analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sonidegib | Summary of Overall Response (ORR) and Clinical Benefit (CBR) | Partial response (PR) | 0 percent responders |
| Sonidegib | Summary of Overall Response (ORR) and Clinical Benefit (CBR) | Complete response (CR) | 0 percent responders |
| Sonidegib | Summary of Overall Response (ORR) and Clinical Benefit (CBR) | Stable disease (SD) | 0 percent responders |
| Sonidegib | Summary of Overall Response (ORR) and Clinical Benefit (CBR) | Progressive disease (PD) | 8 percent responders |
| Sonidegib | Summary of Overall Response (ORR) and Clinical Benefit (CBR) | Non-evaluable (NE) | 2 percent responders |
| Sonidegib | Summary of Overall Response (ORR) and Clinical Benefit (CBR) | Overall response rate (ORR: CR+PR) | 0 percent responders |
| Sonidegib | Summary of Overall Response (ORR) and Clinical Benefit (CBR) | Clinical benefit rate (CBR: CR+PR+SD) | 0 percent responders |
Secondary
Kaplan-Meier Estimates of Progression Free Survival (PFS )Timing, Months
Time frame: 4 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sonidegib | Kaplan-Meier Estimates of Progression Free Survival (PFS )Timing, Months | 1.8 months |
Secondary
Summary of Timing and Estimated Rate for Progression-free Survival (PFS) - 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.
Time frame: 4 months
Population: Full Analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sonidegib | Summary of Timing and Estimated Rate for Progression-free Survival (PFS) - Full Analysis Set | 1 Month | 88.9 % progression free surviors |
| Sonidegib | Summary of Timing and Estimated Rate for Progression-free Survival (PFS) - Full Analysis Set | 2 Months | 33.3 % progression free surviors |
| Sonidegib | Summary of Timing and Estimated Rate for Progression-free Survival (PFS) - Full Analysis Set | 3 Months | 33.3 % progression free surviors |
| Sonidegib | Summary of Timing and Estimated Rate for Progression-free Survival (PFS) - Full Analysis Set | 4 Months | 0.0 % progression free surviors |