SIGNATURE: LDE225 for Patients With PTCH1 or SMO Mutated Tumors
Study Details
Study Description
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: LDE225 LDE225 800 mg (hard gelatin capsules) will be administered orally once daily on a continuous dosing schedule. |
Drug: LDE225
LDE225 800 mg (hard gelatin capsules) will be administered orally once daily on a continuous dosing schedule
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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]
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of California Davis Cancer Center UC Davis Cancer (3) | Sacramento | California | United States | 95817 |
| 2 | Rocky Mountain Cancer Centers RMCC - Aurora | Greenwood Village | Colorado | United States | |
| 3 | Lurie Children's Hospital of Chicago Developmental Therapeutics | Chicago | Illinois | United States | 60611 |
| 4 | Minnesota Oncology Hematology, P.A. Southdate Medical Center | Minneapolis | Minnesota | United States | 55404 |
| 5 | Cleveland Clinic Foundation Cleveland Clinic (19) | Cleveland | Ohio | United States | 44195 |
| 6 | Sanford Research Sanford Health | Sioux Falls | South Dakota | United States | 57104 |
| 7 | Oncology Consultants Oncology Group | Houston | Texas | United States | 77024 |
| 8 | MD Anderson Cancer Center/University of Texas MD Anderson Cancer Center (3) | Houston | Texas | United States | 77030 |
| 9 | Intermountain Medical Center Intermountain Healthcare | Murray | Utah | United States | 84157 |
| 10 | Seattle Cancer Care Alliance Skagit Valley Hospital | Seattle | Washington | United States | 98109-1023 |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CLDE225XUS20
Study Results
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. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Sonidegib |
|---|---|
| Arm/Group Description | 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. |
| Period Title: Overall Study | |
| STARTED | 10 |
| COMPLETED | 0 |
| NOT COMPLETED | 10 |
Baseline Characteristics
| Arm/Group Title | Sonidegib |
|---|---|
| Arm/Group Description | 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 Participants | 10 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
4
40%
|
| >=65 years |
6
60%
|
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
63.2
(7.64)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
6
60%
|
| Male |
4
40%
|
Outcome Measures
| Title | Summary of Overall Response (ORR) and Clinical Benefit (CBR) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set |
| Arm/Group Title | Sonidegib |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 10 |
| Complete response (CR) |
0
|
| Partial response (PR) |
0
|
| Stable disease (SD) |
0
|
| Progressive disease (PD) |
8
|
| Non-evaluable (NE) |
2
|
| Overall response rate (ORR: CR+PR) |
0
|
| Clinical benefit rate (CBR: CR+PR+SD) |
0
|
| Title | Summary of Timing and Estimated Rate for Progression-free Survival (PFS) - Full Analysis Set |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis set |
| Arm/Group Title | Sonidegib |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 10 |
| 1 Month |
88.9
|
| 2 Months |
33.3
|
| 3 Months |
33.3
|
| 4 Months |
0.0
|
| Title | Kaplan-Meier Estimates of Progression Free Survival (PFS )Timing, Months |
|---|---|
| Description | |
| Time Frame | 4 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Sonidegib |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 10 |
| Median (95% Confidence Interval) [months] |
1.8
|
Adverse Events
| Time Frame | ||
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | LDE225 | |
| Arm/Group Description | 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. | |
All Cause Mortality |
||
| LDE225 | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| LDE225 | ||
| Affected / at Risk (%) | # Events | |
| Total | 7/10 (70%) | |
| Gastrointestinal disorders | ||
| Abdominal pain | 2/10 (20%) | |
| Dysphagia | 1/10 (10%) | |
| Small intestinal obstruction | 1/10 (10%) | |
| Infections and infestations | ||
| Pneumonia | 1/10 (10%) | |
| Metabolism and nutrition disorders | ||
| Dehydration | 2/10 (20%) | |
| Failure to thrive | 1/10 (10%) | |
| Musculoskeletal and connective tissue disorders | ||
| Muscular weakness | 1/10 (10%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Chronic obstructive pulmonary disease | 1/10 (10%) | |
| Cough | 1/10 (10%) | |
| Dysphonia | 1/10 (10%) | |
| Dyspnoea | 1/10 (10%) | |
| Pulmonary embolism | 1/10 (10%) | |
Other (Not Including Serious) Adverse Events |
||
| LDE225 | ||
| Affected / at Risk (%) | # Events | |
| Total | 10/10 (100%) | |
| Blood and lymphatic system disorders | ||
| Anaemia | 1/10 (10%) | |
| Gastrointestinal disorders | ||
| Abdominal pain | 2/10 (20%) | |
| Constipation | 3/10 (30%) | |
| Diarrhoea | 3/10 (30%) | |
| Dyspepsia | 1/10 (10%) | |
| Dysphagia | 1/10 (10%) | |
| Nausea | 8/10 (80%) | |
| Vomiting | 4/10 (40%) | |
| General disorders | ||
| Asthenia | 2/10 (20%) | |
| Fatigue | 6/10 (60%) | |
| Oedema peripheral | 1/10 (10%) | |
| Pain | 1/10 (10%) | |
| Infections and infestations | ||
| Urinary tract infection | 3/10 (30%) | |
| Investigations | ||
| Activated partial thromboplastin time prolonged | 1/10 (10%) | |
| Alanine aminotransferase increased | 3/10 (30%) | |
| Aspartate aminotransferase increased | 3/10 (30%) | |
| Blood alkaline phosphatase increased | 2/10 (20%) | |
| Blood creatine phosphokinase increased | 3/10 (30%) | |
| Blood lactate dehydrogenase increased | 1/10 (10%) | |
| Blood uric acid increased | 1/10 (10%) | |
| Gamma-glutamyltransferase increased | 3/10 (30%) | |
| Haemoglobin decreased | 1/10 (10%) | |
| Weight decreased | 4/10 (40%) | |
| White blood cell count decreased | 1/10 (10%) | |
| Metabolism and nutrition disorders | ||
| Decreased appetite | 5/10 (50%) | |
| Dehydration | 1/10 (10%) | |
| Hypercalcaemia | 1/10 (10%) | |
| Hyperglycaemia | 2/10 (20%) | |
| Hypoglycaemia | 1/10 (10%) | |
| Hypomagnesaemia | 1/10 (10%) | |
| Hyponatraemia | 1/10 (10%) | |
| Musculoskeletal and connective tissue disorders | ||
| Arthralgia | 1/10 (10%) | |
| Back pain | 1/10 (10%) | |
| Muscle spasms | 2/10 (20%) | |
| Musculoskeletal chest pain | 1/10 (10%) | |
| Myalgia | 1/10 (10%) | |
| Nervous system disorders | ||
| Dysgeusia | 2/10 (20%) | |
| Headache | 1/10 (10%) | |
| Neuropathy peripheral | 1/10 (10%) | |
| Psychiatric disorders | ||
| Depression | 1/10 (10%) | |
| Irritability | 1/10 (10%) | |
| Renal and urinary disorders | ||
| Proteinuria | 3/10 (30%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Cough | 3/10 (30%) | |
| Dyspnoea | 1/10 (10%) | |
| Pleural effusion | 1/10 (10%) | |
| Skin and subcutaneous tissue disorders | ||
| Alopecia | 2/10 (20%) | |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
| Name/Title | Clinical Disclosure Office |
|---|---|
| Organization | Novartis Pharmaceuticals |
| Phone | 862-778-8300 |
- CLDE225XUS20