Back to resultsA Phase I Clinical Study With Investigational Compound LTT462 in Adult Patients With Specific Advanced Cancers.
Primary Purpose
Ovarian Neoplasms, Non-Small-Cell Lung Carcinoma, Melanoma
Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
LTT462
Sponsored by
About this trial
This is an interventional treatment trial for Ovarian Neoplasms focused on measuring LTT462, ERK, MAPK, solid tumor
Eligibility Criteria
Inclusion Criteria:
- Patient (male or female) ≥12 years of age
- ECOG (Eastern Cooperative Oncology Group) performance status ≤1
- Must have progressed following standard therapy, or for whom, in the opinion of the Investigator, no effective standard therapy exists, is tolerated or appropriate.
- Patients must be willing and able to undergo study required biopsies.
- Presence of at least one measurable lesion according to RECIST v1.1.
- Documented MAPK pathway alteration
Exclusion Criteria:
- Prior treatment with ERK inhibitors.
- History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO.
- Any medical condition that would, in the investigator's judgment, prevent the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures.
- Patients receiving proton pump inhibitors (PPI) which cannot be discontinued 3 days prior to the start study treatment and for the duration of the study.
- Patients with malignant disease other than that being treated in the study.
- Clinically significant cardiac disease.
Other protocol-defined exclusion criteria may apply.
Sites / Locations
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Escalation
Expansion Group 1
Expansion Group 2
Expansion Group 3
Expansion Group 4
Arm Description
Outcomes
Primary Outcome Measures
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An adverse events is defined as the appearance of (or worsening of any pre-existing) undesirable signs, symptoms, or medical conditions that occur after participant's signed informed consent has been obtained. A SAE is described as any adverse event that leads to death, is life threatening, causes or prolongs hospitalization, results in a congenital anomaly, or any other important medical event not described above.
Percentage of Participants With Dose Limiting Toxicities (DLTs)
Percentage of participants with dose limiting toxicity were reported.
Percentage of Participants With at Least One Dose Reduction
Percentage of participants with at least one dose reduction were reported.
Percentage of Participants With at Least One Dose Interruptions
Percentage of participants with at least dose interruptions were reported.
Dose Intensity Received by Participants
Dose intensity of LTT462 received by treatment group was reported.
Secondary Outcome Measures
Percentage of Participants With Overall Response Rate (ORR)
Percentage of participants with overall response rate were reported.
Percentage of Participants With Disease Control Rate (DCR)
Percentage of participants with disease control rate were reported.
Duration of Response (DOR)
DOR is defined as the time between the date of the first documented response (complete response [CR] or partial response [PR]) and the date of progression.
Progression Free Survival (PFS)
Median time for progression free survival was reported.
Overall Survival (OS) - Only for Dose Expansion Phase
Median time for overall survival, only for dose expansion phase was reported.
The Maximum (Peak) Observed Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Cmax) After Single Dose Administration of LTT462
Cmax is the maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration expressed in mass x volume-1.
Area Under the Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of LTT462
AUClast is the area under the curve from time zero to the last measurable concentration sampling time calculated by mass * time *volume^-1
The Time to Reach Maximum (Peak) Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Tmax) After Single Dose Administration of LTT462
Tmax is the time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration.
Elimination Half-life (T1/2) of LTT462
T1/2 is the Elimination half-life.
The Area Under the Curve Calculated to the End of a Dosing Interval (Tau) at Steady-state (AUCtau) of LTT462
AUCtau is the area under the curve calculated to the end of a dosing interval (tau) at steady-state calculated by formula amount *time * volume^-1
Accumulation Ratio (Racc) of LTT462
Racc is the accumulation ratio calculated by AUCtau ratio Day 15 versus Day 1.
Changes From Baseline in Relative Quantity (RQ) of Dual Specificity Phosphatase 6 (DUSP6) in Tumor Tissue and in Blood
Assessment of Pharmacodynamic (PD) effects of LTT462 in tumor, pre- and post- treatment tumor biopsies were examined for expression of DUSP6. For assessment of PD effects in blood, levels of DUSP6 were measured in blood samples.
Full Information
NCT ID
NCT02711345
First Posted
February 16, 2016
Last Updated
August 15, 2019
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT02711345
Brief Title
A Phase I Clinical Study With Investigational Compound LTT462 in Adult Patients With Specific Advanced Cancers.
Official Title
A Phase I Dose Finding Study of Oral LTT462 in Adult Patients With Advanced Solid Tumors Harboring MAPK Pathway Alterations.
Study Type
Interventional
2. Study Status
Record Verification Date
August 2019
Overall Recruitment Status
Terminated
Why Stopped
considering the limited clinical activity observed with LTT462, the decision was made to not open the dose expansion phase of the study
Study Start Date
April 15, 2016 (Actual)
Primary Completion Date
November 21, 2018 (Actual)
Study Completion Date
November 21, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
A phase I study of LTT462 in patients with advanced solid tumors that harbor MAPK pathway alterations.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Neoplasms, Non-Small-Cell Lung Carcinoma, Melanoma, Other Solid Tumors
Keywords
LTT462, ERK, MAPK, solid tumor
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
65 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Escalation
Arm Type
Experimental
Arm Title
Expansion Group 1
Arm Type
Experimental
Arm Title
Expansion Group 2
Arm Type
Experimental
Arm Title
Expansion Group 3
Arm Type
Experimental
Arm Title
Expansion Group 4
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
LTT462
Intervention Description
ERK Inhibitor
Primary Outcome Measure Information:
Title
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
An adverse events is defined as the appearance of (or worsening of any pre-existing) undesirable signs, symptoms, or medical conditions that occur after participant's signed informed consent has been obtained. A SAE is described as any adverse event that leads to death, is life threatening, causes or prolongs hospitalization, results in a congenital anomaly, or any other important medical event not described above.
Time Frame
Up to 2.8 years
Title
Percentage of Participants With Dose Limiting Toxicities (DLTs)
Description
Percentage of participants with dose limiting toxicity were reported.
Time Frame
Up to 2.8 years
Title
Percentage of Participants With at Least One Dose Reduction
Description
Percentage of participants with at least one dose reduction were reported.
Time Frame
Up to 2.8 years
Title
Percentage of Participants With at Least One Dose Interruptions
Description
Percentage of participants with at least dose interruptions were reported.
Time Frame
Up to 2.8 years
Title
Dose Intensity Received by Participants
Description
Dose intensity of LTT462 received by treatment group was reported.
Time Frame
Up to 2.8 years
Secondary Outcome Measure Information:
Title
Percentage of Participants With Overall Response Rate (ORR)
Description
Percentage of participants with overall response rate were reported.
Time Frame
Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years)
Title
Percentage of Participants With Disease Control Rate (DCR)
Description
Percentage of participants with disease control rate were reported.
Time Frame
Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years)
Title
Duration of Response (DOR)
Description
DOR is defined as the time between the date of the first documented response (complete response [CR] or partial response [PR]) and the date of progression.
Time Frame
Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years)
Title
Progression Free Survival (PFS)
Description
Median time for progression free survival was reported.
Time Frame
Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years)
Title
Overall Survival (OS) - Only for Dose Expansion Phase
Description
Median time for overall survival, only for dose expansion phase was reported.
Time Frame
Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years)
Title
The Maximum (Peak) Observed Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Cmax) After Single Dose Administration of LTT462
Description
Cmax is the maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration expressed in mass x volume-1.
Time Frame
day 1, day 15
Title
Area Under the Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of LTT462
Description
AUClast is the area under the curve from time zero to the last measurable concentration sampling time calculated by mass * time *volume^-1
Time Frame
Cycle 1 Days 1, 2, 3, 8, 15 and 16; Cycle 2 day 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1
Title
The Time to Reach Maximum (Peak) Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Tmax) After Single Dose Administration of LTT462
Description
Tmax is the time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration.
Time Frame
day 1, day 15
Title
Elimination Half-life (T1/2) of LTT462
Description
T1/2 is the Elimination half-life.
Time Frame
Cycle 1 Days 1, 2, 3, 8, 15 and 16; Cycle 2 day 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1
Title
The Area Under the Curve Calculated to the End of a Dosing Interval (Tau) at Steady-state (AUCtau) of LTT462
Description
AUCtau is the area under the curve calculated to the end of a dosing interval (tau) at steady-state calculated by formula amount *time * volume^-1
Time Frame
Cycle 1 Days 1, 2, 3, 8, 15 and 16; Cycle 2 day 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1
Title
Accumulation Ratio (Racc) of LTT462
Description
Racc is the accumulation ratio calculated by AUCtau ratio Day 15 versus Day 1.
Time Frame
Cycle 1 Days 1, 2, 3, 8, 15 and 16; Cycle 2 day 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1
Title
Changes From Baseline in Relative Quantity (RQ) of Dual Specificity Phosphatase 6 (DUSP6) in Tumor Tissue and in Blood
Description
Assessment of Pharmacodynamic (PD) effects of LTT462 in tumor, pre- and post- treatment tumor biopsies were examined for expression of DUSP6. For assessment of PD effects in blood, levels of DUSP6 were measured in blood samples.
Time Frame
Cycle 1 Days 1, 2, 3, 15 and 16
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patient (male or female) ≥12 years of age
ECOG (Eastern Cooperative Oncology Group) performance status ≤1
Must have progressed following standard therapy, or for whom, in the opinion of the Investigator, no effective standard therapy exists, is tolerated or appropriate.
Patients must be willing and able to undergo study required biopsies.
Presence of at least one measurable lesion according to RECIST v1.1.
Documented MAPK pathway alteration
Exclusion Criteria:
Prior treatment with ERK inhibitors.
History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO.
Any medical condition that would, in the investigator's judgment, prevent the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures.
Patients receiving proton pump inhibitors (PPI) which cannot be discontinued 3 days prior to the start study treatment and for the duration of the study.
Patients with malignant disease other than that being treated in the study.
Clinically significant cardiac disease.
Other protocol-defined exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Novartis Investigative Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-4009
Country
United States
Facility Name
Novartis Investigative Site
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Novartis Investigative Site
City
Chuo ku
State/Province
Tokyo
ZIP/Postal Code
104 0045
Country
Japan
Facility Name
Novartis Investigative Site
City
Singapore
ZIP/Postal Code
169610
Country
Singapore
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08035
Country
Spain
Facility Name
Novartis Investigative Site
City
Bellinzona
ZIP/Postal Code
6500
Country
Switzerland
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Phase I Clinical Study With Investigational Compound LTT462 in Adult Patients With Specific Advanced Cancers.
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