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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 : Terminated (considering the limited clinical activity observed with LTT462, the decision was made to not open the dose expansion phase of the study)
First Posted : March 17, 2016
Results First Posted : September 19, 2019
Last Update Posted : September 19, 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. Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to 2.8 years ]
    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.

  2. Percentage of Participants With Dose Limiting Toxicities (DLTs) [ Time Frame: Up to 2.8 years ]
    Percentage of participants with dose limiting toxicity were reported.

  3. Percentage of Participants With at Least One Dose Reduction [ Time Frame: Up to 2.8 years ]
    Percentage of participants with at least one dose reduction were reported.

  4. Percentage of Participants With at Least One Dose Interruptions [ Time Frame: Up to 2.8 years ]
    Percentage of participants with at least dose interruptions were reported.

  5. Dose Intensity Received by Participants [ Time Frame: Up to 2.8 years ]
    Dose intensity of LTT462 received by treatment group was reported.


Secondary Outcome Measures :
  1. Percentage of Participants With Overall Response Rate (ORR) [ Time Frame: Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years) ]
    Percentage of participants with overall response rate were reported.

  2. Percentage of Participants With Disease Control Rate (DCR) [ Time Frame: Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years) ]
    Percentage of participants with disease control rate were reported.

  3. Duration of Response (DOR) [ Time Frame: Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years) ]
    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.

  4. Progression Free Survival (PFS) [ Time Frame: Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years) ]
    Median time for progression free survival was reported.

  5. Overall Survival (OS) - Only for Dose Expansion Phase [ Time Frame: Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years) ]
    Median time for overall survival, only for dose expansion phase was reported.

  6. The Maximum (Peak) Observed Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Cmax) After Single Dose Administration of LTT462 [ Time Frame: day 1, day 15 ]
    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.

  7. Area Under the Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of LTT462 [ 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 ]
    AUClast is the area under the curve from time zero to the last measurable concentration sampling time calculated by mass * time *volume^-1

  8. The Time to Reach Maximum (Peak) Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Tmax) After Single Dose Administration of LTT462 [ Time Frame: day 1, day 15 ]
    Tmax is the time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration.

  9. Elimination Half-life (T1/2) of LTT462 [ 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 ]
    T1/2 is the Elimination half-life.

  10. The Area Under the Curve Calculated to the End of a Dosing Interval (Tau) at Steady-state (AUCtau) of LTT462 [ 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 ]
    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

  11. Accumulation Ratio (Racc) of LTT462 [ 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 ]
    Racc is the accumulation ratio calculated by AUCtau ratio Day 15 versus Day 1.

  12. Changes From Baseline in Relative Quantity (RQ) of Dual Specificity Phosphatase 6 (DUSP6) in Tumor Tissue and in Blood [ Time Frame: Cycle 1 Days 1, 2, 3, 15 and 16 ]
    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.



Information from the National Library of Medicine

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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
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
  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):
Study Protocol  [PDF] March 13, 2018
Statistical Analysis Plan  [PDF] May 13, 2019

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02711345    
Other Study ID Numbers: CLTT462X2101
2015-003614-24 ( EudraCT Number )
First Posted: March 17, 2016    Key Record Dates
Results First Posted: September 19, 2019
Last Update Posted: September 19, 2019
Last Verified: August 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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Carcinoma, Non-Small-Cell Lung
Ovarian Neoplasms
Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
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