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

NCT02711345 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: CLTT462X21012015-003614-24
• Study Type: interventional
• Target: 65
• Locations: 6 countries
• Sites: 7

Brief Summary

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

Conditions

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

Keywords

LTT462; ERK; MAPK; solid tumor

Outcome Measures

Primary Outcomes (5)

• 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

• Percentage of Participants With Dose Limiting Toxicities (DLTs)

  Percentage of participants with dose limiting toxicity were reported.

  Up to 2.8 years

• 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

• Percentage of Participants With at Least One Dose Interruptions

  Percentage of participants with at least dose interruptions were reported.

  Up to 2.8 years

• Dose Intensity Received by Participants

  Dose intensity of LTT462 received by treatment group was reported.

  Up to 2.8 years

Secondary Outcomes (12)

• Percentage of Participants With Overall Response Rate (ORR)

  Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years)

• Percentage of Participants With Disease Control Rate (DCR)

  Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years)

• Duration of Response (DOR)

  Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years)

• Progression Free Survival (PFS)

  Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years)

• Overall Survival (OS) - Only for Dose Expansion Phase

  Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years)

Study Arms (5)

Escalation

EXPERIMENTAL

Drug: LTT462

Expansion Group 1

EXPERIMENTAL

Drug: LTT462

Expansion Group 2

EXPERIMENTAL

Drug: LTT462

Expansion Group 3

EXPERIMENTAL

Drug: LTT462

Expansion Group 4

EXPERIMENTAL

Drug: LTT462

Interventions

LTT462 DRUG

ERK Inhibitor

Escalation; Expansion Group 1; Expansion Group 2; Expansion Group 3; Expansion Group 4

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (7)

Novartis Investigative Site

New York, New York, 10065, United States

Location

Novartis Investigative Site

Houston, Texas, 77030-4009, United States

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

Chuo Ku, Tokyo, 104 0045, Japan

Location

Novartis Investigative Site

Singapore, 169610, Singapore

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Bellinzona, 6500, Switzerland

Location

MeSH Terms

Conditions

Ovarian Neoplasms; Carcinoma, Non-Small-Cell Lung; Melanoma

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Limitations and Caveats

Following careful evaluation of the available study data and considering the limited clinical activity observed with LTT462, the decision was made to not open the dose expansion phase of the study and the study was terminated early.

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharma AG

Novartis.email@novartis.com

862 778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 16, 2016
• First Posted: March 17, 2016
• Study Start: April 15, 2016
• Primary Completion: November 21, 2018
• Study Completion: November 21, 2018
• Last Updated: September 19, 2019
• Results First Posted: September 19, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1); DE (1); SG (1); CH (1); JP (1); US (2)