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Dose Finding Study of TNO155 in Adult Patients With Advanced Solid Tumors

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified April 2017 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT03114319
First received: April 11, 2017
Last updated: April 20, 2017
Last verified: April 2017
  Purpose
The purpose of this first in human (FIH) trial is to characterize the safety and tolerability of the SHP2 inhibitor TNO155 and identify a recommended dose for future studies in adult patients with advanced solid tumors in selected indications.

Condition Intervention Phase
Advanced EGFR-mutant Non-smallcell Lung Cancer
Head-and-Neck Squamous Cell Cancer
RAS/RAF Wild-type Other Solid Tumors
Drug: TNO155
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: An Open-label, Multi-center, Phase I, Dose Finding Study of Oral TNO155 in Adult Patients With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Number of participants with adverse events [ Time Frame: up to 3 years; at least once per treatment cycle ]
    All patients participating in this study will be assessed for incidence and severity of adverse events (AEs) and serious AEs, including changes in laboratory values, vital signs, electrocardiograms, cardiac imaging and ophthalmological assessments

  • Number of participants with dose limiting toxicities [ Time Frame: up to 28-day cycle ]
    Incidence and nature of dose limiting toxicities (DLTs) in the dose escalation part. A DLT is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first treatment cycle (either 21 days or 28 days, depending on the cohort's treatment schedule) with TNO155


Secondary Outcome Measures:
  • Area under the curve [ Time Frame: 30 months ]
    Area under the plasma concentration time curve of TNO155

  • Overall response rate [ Time Frame: From start of treatment for 34 months ]
    To evaluate the preliminary anti-tumor activity of TNO155, e.g., overall response rate per RECIST 1.1

  • pERK [ Time Frame: At screening and between Cycle 1 and Cycle 3 on treatment for 30 months ]
    On treatment versus baseline comparison of pharmacodynamic markers e.g., pERK (Phosphorylated form of Extracellular signal-regulated kinase) on newly obtained tumor samples by IHC

  • Cmax [ Time Frame: 30 months ]
    highest observed plasma concentration of TNO155

  • tmax [ Time Frame: 30 months ]
    Time of highest observed plasma concentration of TNO155

  • apparent terminal elimination half-life [ Time Frame: 30 months ]
    terminal elimination half-life of TNO155


Estimated Enrollment: 105
Anticipated Study Start Date: April 25, 2017
Estimated Study Completion Date: February 11, 2020
Estimated Primary Completion Date: February 11, 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TNO155
TNO155 for oral administration
Drug: TNO155
TNO155 for oral administration

Detailed Description:
This study has been designed as a Phase I, open-label, dose finding study with a dose escalation part and a dose expansion part in adult patients with selected advanced solid tumors. The study treatment, TNO155, will be taken until the patient experiences unacceptable toxicity, progressive disease and/or treatment is discontinued at the discretion of the investigator or the patient or due to withdrawal of consent. Some patients will be participating in a food effect investigation as an exploratory objective.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Able to understand and voluntarily sign the ICF and able to comply with the study visit schedule and the other protocol requirements.
  2. Patient (male or female) ≥18 years of age willing to agree to not father a child/become pregnant and comply with effective contraception criteria.
  3. Must have progressed following standard therapy, or for whom, in the opinion of the Investigator, no effective standard therapy exists, is tolerated or is appropriate.
  4. ECOG (Eastern cooperative oncology group) performance status ≤2

Exclusion Criteria:

  1. Tumors harboring known activating KRAS, NRAS, HRAS, BRAF or PTPN11 (SHP2) mutations.
  2. History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO.
  3. 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.
  4. Clinically significant cardiac disease.
  5. Active diarrhea or inflammatory bowel disease
  6. Insufficient bone marrow function
  7. Insufficient hepatic and renal function.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03114319

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682 trialsandresults.registries@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03114319     History of Changes
Other Study ID Numbers: CTNO155X2101
2016-001861-10 ( EudraCT Number )
Study First Received: April 11, 2017
Last Updated: April 20, 2017
Individual Participant Data  
Plan to Share IPD: No

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

Keywords provided by Novartis:
TNO155
SHP2
advanced solid tumor
NSCLC
HNSCC
EGFR
GIST
PTPN11
cancers with a mass
bulky tumor
nodule
lump
advanced solid malignancies

Additional relevant MeSH terms:
Neoplasms, Squamous Cell
Carcinoma, Squamous Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma

ClinicalTrials.gov processed this record on April 27, 2017