Clinical trial NCT02711345: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: Ovarian Neoplasms
Non-Small-Cell Lung Carcinoma
Melanoma
Other Solid Tumors
Keywords: LTT462
ERK
MAPK
solid tumor
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2016-03-17
Enrollment: 65
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


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.

Primary outcomes:
measure: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to 2.8 years
measure: Percentage of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: Up to 2.8 years
measure: Percentage of Participants With at Least One Dose Reduction
timeFrame: Up to 2.8 years
measure: Percentage of Participants With at Least One Dose Interruptions
timeFrame: Up to 2.8 years
measure: Dose Intensity Received by Participants
timeFrame: Up to 2.8 years
Secondary outcomes:
measure: Percentage of Participants With Overall Response Rate (ORR)
timeFrame: Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years)
measure: Percentage of Participants With Disease Control Rate (DCR)
timeFrame: Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years)
measure: Duration of Response (DOR)
timeFrame: Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years)
measure: Progression Free Survival (PFS)
timeFrame: Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years)
measure: Overall Survival (OS) - Only for Dose Expansion Phase
timeFrame: Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years)
measure: The Maximum (Peak) Observed Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Cmax) After Single Dose Administration of LTT462
timeFrame: day 1, day 15
measure: Area Under the Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of LTT462
timeFrame: Cycle 1 Days 1, 2, 3, 8, 15 and 16; Cycle 2 day 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1
measure: The Time to Reach Maximum (Peak) Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Tmax) After Single Dose Administration of LTT462
timeFrame: day 1, day 15
measure: Elimination Half-life (T1/2) of LTT462
timeFrame: Cycle 1 Days 1, 2, 3, 8, 15 and 16; Cycle 2 day 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1
measure: The Area Under the Curve Calculated to the End of a Dosing Interval (Tau) at Steady-state (AUCtau) of LTT462
timeFrame: Cycle 1 Days 1, 2, 3, 8, 15 and 16; Cycle 2 day 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1
measure: Accumulation Ratio (Racc) of LTT462
timeFrame: Cycle 1 Days 1, 2, 3, 8, 15 and 16; Cycle 2 day 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1
measure: Changes From Baseline in Relative Quantity (RQ) of Dual Specificity Phosphatase 6 (DUSP6) in Tumor Tissue and in Blood
timeFrame: Cycle 1 Days 1, 2, 3, 15 and 16
Other outcomes:
Locations:
city: New York
country: United States
facility: Novartis Investigative Site
state: New York
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Chuo ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Bellinzona
country: Switzerland
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: