A Phase I Clinical Study With Investigational Compound LTT462 in Adult Patients With Specific Advanced Cancers.

Melanoma Clinical Trial

Official title:

A Phase I Dose Finding Study of Oral LTT462 in Adult Patients With Advanced Solid Tumors Harboring MAPK Pathway Alterations.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02711345
• Other study ID #: CLTT462X2101
• Secondary ID: 2015-003614-24
• Status: Terminated
• Phase: Phase 1
• Start date: April 15, 2016
• Est. completion date: November 21, 2018

Study information

• Verified date: August 2019
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A phase I study of LTT462 in patients with advanced solid tumors that harbor MAPK pathway alterations.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 65
• Est. completion date: November 21, 2018
• Est. primary completion date: November 21, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Melanoma
• Non-Small-Cell Lung Carcinoma
• Other Solid Tumors
• Ovarian Neoplasms

Intervention

Drug:
• LTT462
ERK Inhibitor

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Essen
Japan	Novartis Investigative Site	Chuo ku	Tokyo
Singapore	Novartis Investigative Site	Singapore
Spain	Novartis Investigative Site	Barcelona	Catalunya
Switzerland	Novartis Investigative Site	Bellinzona
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Germany,  Japan,  Singapore,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 2.8 years
Primary	Percentage of Participants With Dose Limiting Toxicities (DLTs)	Percentage of participants with dose limiting toxicity were reported.	Up to 2.8 years
Primary	Percentage of Participants With at Least One Dose Reduction	Percentage of participants with at least one dose reduction were reported.	Up to 2.8 years
Primary	Percentage of Participants With at Least One Dose Interruptions	Percentage of participants with at least dose interruptions were reported.	Up to 2.8 years
Primary	Dose Intensity Received by Participants	Dose intensity of LTT462 received by treatment group was reported.	Up to 2.8 years
Secondary	Percentage of Participants With Overall Response Rate (ORR)	Percentage of participants with overall response rate were reported.	Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years)
Secondary	Percentage of Participants With Disease Control Rate (DCR)	Percentage of participants with disease control rate were reported.	Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years)
Secondary	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.	Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years)
Secondary	Progression Free Survival (PFS)	Median time for progression free survival was reported.	Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years)
Secondary	Overall Survival (OS) - Only for Dose Expansion Phase	Median time for overall survival, only for dose expansion phase was reported.	Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years)
Secondary	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.	day 1, day 15
Secondary	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	Cycle 1 Days 1, 2, 3, 8, 15 and 16; Cycle 2 day 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1
Secondary	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.	day 1, day 15
Secondary	Elimination Half-life (T1/2) of LTT462	T1/2 is the Elimination half-life.	Cycle 1 Days 1, 2, 3, 8, 15 and 16; Cycle 2 day 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1
Secondary	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	Cycle 1 Days 1, 2, 3, 8, 15 and 16; Cycle 2 day 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1
Secondary	Accumulation Ratio (Racc) of LTT462	Racc is the accumulation ratio calculated by AUCtau ratio Day 15 versus Day 1.	Cycle 1 Days 1, 2, 3, 8, 15 and 16; Cycle 2 day 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1
Secondary	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.	Cycle 1 Days 1, 2, 3, 15 and 16