A 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.
Triple-negative Breast Cancer
Head and Neck Cancer
Other Tumor Types With Documented Genetic Alterations Upstream in the Wnt Signaling Pathway
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I, Open-label, Dose Escalation Study of Oral LGK974 in Patients With Malignancies Dependent on Wnt Ligands|
- 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.
- 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.
|Study Start Date:||February 2012|
|Estimated Study Completion Date:||August 2015|
|Estimated Primary Completion Date:||August 2015 (Final data collection date for primary outcome measure)|
|Contact: Novartis Pharmaceuticals||1-888-669-6682|
|Contact: Novartis Pharmaceuticals|
|United States, Maryland|
|The Sidney Kimmel Cancer Center at Johns Hopkins Hospital Johns Hopkins||Recruiting|
|Baltimore, Maryland, United States, 21231|
|Contact: Ashley OConnor 410-502-2377 email@example.com|
|Principal Investigator: Roisin Connolly|
|United States, Massachusetts|
|Dana Farber Cancer Institute SC||Withdrawn|
|Boston, Massachusetts, United States, 02115|
|United States, Michigan|
|Wayne State University/Karmanos Cancer Institute Wayne St||Recruiting|
|Detroit, Michigan, United States, 48201|
|Contact: Taylor Brewer 313-576-8096 firstname.lastname@example.org|
|Principal Investigator: Patricia M. LoRusso|
|United States, Texas|
|University of Texas/MD Anderson Cancer Center MD Anderson 2||Recruiting|
|Houston, Texas, United States, 77030-4009|
|Contact: Stepanek Vanda +1 713 792 2921 email@example.com|
|Principal Investigator: Sapna Pradyuman Patel|
|Novartis Investigative Site||Recruiting|
|Rotterdam, Netherlands, 3075 EA|
|Novartis Investigative Site||Recruiting|
|Barcelona, Cataluña, Spain, 08035|
|Study Director:||Novartis Pharmaceuticals||Novartis Pharmaceuticals|