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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02711345
Recruitment Status : Completed
First Posted : March 17, 2016
Last Update Posted : April 11, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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

Condition or disease Intervention/treatment Phase
Ovarian Neoplasms Non-Small-Cell Lung Carcinoma Melanoma Other Solid Tumors Drug: LTT462 Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 65 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Dose Finding Study of Oral LTT462 in Adult Patients With Advanced Solid Tumors Harboring MAPK Pathway Alterations.
Actual Study Start Date : April 15, 2016
Actual Primary Completion Date : November 21, 2018
Actual Study Completion Date : November 21, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Escalation Drug: LTT462
ERK Inhibitor

Experimental: Expansion Group 1 Drug: LTT462
ERK Inhibitor

Experimental: Expansion Group 2 Drug: LTT462
ERK Inhibitor

Experimental: Expansion Group 3 Drug: LTT462
ERK Inhibitor

Experimental: Expansion Group 4 Drug: LTT462
ERK Inhibitor




Primary Outcome Measures :
  1. Safety and tolerability as assessed by incidence and severity of adverse events (AEs), dose interruptions, reductions, and dose intensity [ Time Frame: From Cycle 1 Day 1 until 30 days post study treatment (expected duration approximately 12 months) ]
  2. Incidence and nature of dose limiting toxicities (DLTs) (dose escalation only) [ Time Frame: 1 cycle (28 days). ]

Secondary Outcome Measures :
  1. Overall response rate (ORR) [ Time Frame: Every 2 cycles after starting LTT462 treatment until end of treatment; expected duration approximately 12 months ]
  2. Disease Control Rate (DCR) [ Time Frame: Every 2 cycles after starting LTT462 treatment until end of treatment; expected duration approximately 12 months ]
  3. Duration of Response (DOR) [ Time Frame: Every 2 cycles after starting LTT462 treatment until end of treatment; expected duration approximately 12 months ]
  4. Progression Free Survival (PFS) [ Time Frame: Every 2 cycles after starting LTT462 treatment until dieseas progression; expected duration approximately 12 months ]
  5. Overall survival (OS) - only for dose expansion phase [ Time Frame: From start of treatment until the date of death; expected duration approximately 12 months ]
  6. Plasma concentrations of LTT462 [ Time Frame: Cycle 1 days 1, 2, 3, 8, 15, 16 and 17; Cycle 2 days 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1 ]
  7. Derived PK parameters of LTT462: Area under the curve (AUC) [ Time Frame: Cycle 1 days 1, 2, 3, 8, 15, 16 and 17; Cycle 2 days 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1 ]
  8. Derived PK parameters of LTT462: Peak Plasma Concentration (Cmax) [ Time Frame: Cycle 1 days 1, 2, 3, 8, 15, 16 and 17; Cycle 2 days 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1 ]
  9. Derived PK parameters of LTT462: Time to Peak Plasma Concentration (Tmax) [ Time Frame: Cycle 1 days 1, 2, 3, 8, 15, 16 and 17; Cycle 2 days 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1 ]
  10. Derived PK parameters of LTT462: half-life (T1/2) [ Time Frame: Cycle 1 days 1, 2, 3, 8, 15, 16 and 17; Cycle 2 days 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1 ]
  11. Changes from baseline of the PD marker DUSP6 in tumor tissue and in blood - dose expansion only [ Time Frame: Cycle 1 day 1, 2, 3, 15, 16 and 17; upon disease progression (expected duration approximately 12 months) ]


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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02711345


Locations
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United States, New York
Novartis Investigative Site
New York, New York, United States, 10065
United States, Texas
Novartis Investigative Site
Houston, Texas, United States, 77030-4009
Germany
Novartis Investigative Site
Essen, Germany, 45147
Japan
Novartis Investigative Site
Chuo ku, Tokyo, Japan, 104 0045
Netherlands
Novartis Investigative Site
Amsterdam, Netherlands, 1066 CX
Singapore
Novartis Investigative Site
Singapore, Singapore, 169610
Spain
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08035
Switzerland
Novartis Investigative Site
Bellinzona, Switzerland, 6500
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02711345     History of Changes
Other Study ID Numbers: CLTT462X2101
2015-003614-24 ( EudraCT Number )
First Posted: March 17, 2016    Key Record Dates
Last Update Posted: April 11, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
LTT462
ERK
MAPK
solid tumor

Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Ovarian Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Endocrine Gland Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders