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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01351103
First received: May 4, 2011
Last updated: March 31, 2014
Last verified: March 2014

May 4, 2011
March 31, 2014
February 2012
August 2015   (final data collection date for primary outcome measure)
Maximum Tolerated Dose or Recommended Dose for Expansion of LGK974 in patients treated [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
Determine the Maximum Tolerated Dose (MTD) or Recommended Dose for Expansion (RDE) of LGK974 as a single agent 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 ] [ Designated as safety issue: Yes ]
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: 18 months ] [ Designated as safety issue: Yes ]
    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 class, type of AE and dose group.
  • Absorption and plasma concentrations of LGK974 [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    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: 18 months ] [ Designated as safety issue: No ]
    Assessing percent change from baseline to post-treatment of biomarkers related to the Wnt pathway.
  • Overall response rate of tumor [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    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. 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.
  • Type and category of study drug related adverse events [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
  • Absorption and plasma concentrations of LGK974 [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Biomarkers related to the Wnt pathway [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Overall response rate of tumor [ Time Frame: 18 months ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Study of Oral 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 that can be safely given to adult patients with malignancies dependent on Wnt ligands for whom no effective standard treatment is available.

Not Provided
Interventional
Phase 1
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Melanoma
  • Breast Neoplasms
  • Lobular Carcinoma
  • Triple-negative Breast Cancer
  • Pancreatic Adenocarcinoma
  • Colorectal Cancer
  • Head and Neck Cancer
  • Other Tumor Types With Documented Genetic Alterations Upstream in the Wnt Signaling Pathway
Drug: LGK974
Experimental: LGK974
Intervention: Drug: LGK974
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
80
August 2015
August 2015   (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:

Dose escalation part: breast cancer (lobular or triple-negative); documented B-RAF mutant colorectal cancer; head and neck squamous cell 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.

Dose expansion part: breast cancer (lobular or triple-negative); head and neck squamous cell cancer; documented B-RAF mutant colorectal cancer with documented Wnt pathway alteration; pancreatic adenocarcinoma with documented Wnt pathway alteration. In addition, patients with tumors of any histological origin with documented genetic alterations upstream in the Wnt signaling pathway are eligible with prior agreement with Novartis

• Site of disease that can be biopsied

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

Other protocol-defined inclusion/exclusion criteria may apply

Both
18 Years and older
No
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals
United States,   Netherlands,   Spain
 
NCT01351103
CLGK974X2101, 2011-000495-33
Not Provided
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
March 2014

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