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A Study of LGK974 in Patients With Malignancies Dependent on Wnt Ligands

This study is currently recruiting participants.
Verified November 2017 by Novartis ( Novartis Pharmaceuticals )
Sponsor:
ClinicalTrials.gov Identifier:
NCT01351103
First Posted: May 10, 2011
Last Update Posted: November 17, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
May 4, 2011
May 10, 2011
November 17, 2017
December 1, 2011
September 25, 2018   (Final data collection date for primary outcome measure)
Maximum Tolerated Dose or Recommended Dose for Expansion of LGK974 as a single agent or in combination with PDR001 in patients treated [ Time Frame: 34 months ]
Determine the Maximum Tolerated Dose (MTD) or Recommended Dose for Expansion (RDE) of LGK974 as a single agent and in combination with PDR001 when administered orally to adult patients with malignancies dependent on Wnt ligands.
Maximum Tolerated Dose of LGK974 in patients treated daily [ Time Frame: 12 months ]
Complete list of historical versions of study NCT01351103 on ClinicalTrials.gov Archive Site
  • Type and category of study drug related adverse events (AE) [ Time Frame: 61 months ]
    The incidence of treatment-emergent adverse events (new or worsening from baseline) will be summarized by primary system organ class, severity based on the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03, type of AE, relationship to study drug by dose group. Deaths reportable as SAEs and non-fatal serious adverse events will be listed by patient and tabulated by primary system organ clase, type of AE and dose group.
  • Absorption and plasma concentrations of LGK974 [ Time Frame: 61 months ]
    Evaluate pharmacokinetic (PK) parameters such as AUClast, AUCtau, Cmax, the apparent elimination T1/2 and Racc for LGK974 and its pharmacologically metabolite. This will include but is not limited to the following timepoints: 8 times at C1D1; C1D2, C1D8, C1D16 and C1D22 pre-dose; 8 times at C1D15; and then pre-dose for each subsequent cycles D1.
  • Biomarkers related to the Wnt pathway [ Time Frame: 61 months ]
    Assessing percent change from baseline to post-treatment of biomarkers related to the Wnt pathway.
  • Overall response rate of tumor [ Time Frame: 61 months ]
    Patients with an Objective Overall Response (OOR) were those whose best response to treatment was a complete response (CR) or a partial response (PR) assessed by RECIST 1.1 or irRC . A patient had a CR if the target tumors disappeared. A patient had a PR if there was a ≥ 30% reduction in the sum of the products of the largest perpendicular diameters of the target tumors compared to the baseline value. Duration of Response (DOR) will also be summarized and is defined as the time from first observation of response to the first time of progression or death.
  • Absorportion and plasma concentrations of PDR001 [ Time Frame: 61 months ]
    Evaluate pharmacokinetic (PK) parameters such as AUClast, AUCtau, Cmax, the apparent elimination T1/2 and Racc for LGK974, its pharmacologically metabolite and PDR001. Serial timpoints will be obtained on C1D1 and within C1 dosing, pre-dose samples may also be obtained during study treatment..
  • Biomarkers related to immunomodulation [ Time Frame: 61 months ]
    Evaluate biomarkers of immunomodulation after treatment with LGK974 and PDR001.
  • Type and category of study drug related adverse events [ Time Frame: 18 months ]
  • Absorption and plasma concentrations of LGK974 [ Time Frame: 18 months ]
  • Biomarkers related to the Wnt pathway [ Time Frame: 18 months ]
  • Overall response rate of tumor [ Time Frame: 18 months ]
Not Provided
Not Provided
 
A Study of LGK974 in Patients With Malignancies Dependent on Wnt Ligands
A Phase I, Open-label, Dose Escalation Study of Oral LGK974 in Patients With Malignancies Dependent on Wnt Ligands
This primary purpose of this study is to find the recommended dose of LGK974 as a single agent and in combination with PDR001 that can be safely given to adult patients with selected solid malignancies for whom no effective standard treatment is available.
Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Pancreatic Cancer
  • BRAF Mutant Colorectal Cancer
  • Other Tumor Types With Documented Genetic Alterations Upstream in the Wnt Signaling Pathway
  • Melanoma
  • Triple Negative Breast Cancer
  • Head and Neck Cancer
  • Drug: LGK974
  • Biological: PDR001
  • Experimental: LGK974
    Intervention: Drug: LGK974
  • Experimental: LGK974 in combination with PDR001
    Intervention: Biological: PDR001
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
170
January 10, 2020
September 25, 2018   (Final data collection date for primary outcome measure)

Inclusion Criteria:

Diagnosis of locally advanced or metastatic cancer that has progressed despite standard therapy or for which no effective standard therapy exists and histological confirmation of one of the following diseases indicated below:

Single Agent Dose escalation part:documented B-RAF mutant colorectal cancer or pancreatic adenocarcinoma. In addition, tumors of any histological origin with documented genetic alterations upstream in the Wnt signaling pathway are eligible with prior agreement with Novartis.

Single Agent Dose expansion part: documented B-RAF mutant colorectal cancer with documented RNF43 mutation and/or RSPO fusion or pancreatic adenocarcinoma with documented RNF43 mutation. In addition, patients with tumors of any histological origin with documented genetic alterations upstream in the Wnt signaling pathway (e.g. RNF43 or RSPO fusion) are eligible with prior agreement with Novartis

LGK974 with PDR001: Dose escalation: melanoma patients primary refractory to anti-PD-1 inhibitor. Dose expansion: patients with pancreatic cancer, or TNBC, or melanoma, or head and neck cancer.

Exclusion Criteria:

  • Impaired cardiac function
  • Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of oral LGK974 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection)
  • Brain metastases that have not been adequately treated
  • Malignant disease other than that being treated in this study
  • Laboratory abnormalities as specified in the protocol
  • Osteoporosis, severe or untreated osteopenia
  • Bone fractures within the past year
  • Pathologic bone fracture
  • Active, known or suspected autoimmune disease or severe hypersensitivity reactions to other monoclonal antibodies

Other protocol-defined inclusion/exclusion criteria may apply

Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact: Novartis Pharmaceuticals 1-888-669-6682 Novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111
Netherlands,   Spain,   United States
 
 
NCT01351103
CLGK974X2101
2011-000495-33 ( EudraCT Number )
No
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Plan to Share IPD: No
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
November 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP