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

This study has suspended participant recruitment.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01351103
First received: May 4, 2011
Last updated: April 15, 2016
Last verified: April 2016
  Purpose
This primary purpose of this study is to find the recommended dose of LGK974 that can be safely given to adult patients with maliganacies dependent on Wnt ligands for whom no effective standard treatment is available.

Condition Intervention Phase
Pancreatic Adenocarcinoma
BRAF Mutant Colorectal Cancer
Other Tumor Types With Documented Genetic Alterations Upstream in the Wnt Signaling Pathway
Drug: LGK974
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
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

Further study details as provided by Novartis:

Primary Outcome Measures:
  • Maximum Tolerated Dose or Recommended Dose for Expansion of LGK974 in patients treated [ Time Frame: 34 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.


Secondary Outcome Measures:
  • Type and category of study drug related adverse events (AE) [ Time Frame: 61 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 clase, type of AE and dose group.

  • Absorption and plasma concentrations of LGK974 [ Time Frame: 61 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: 61 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: 61 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.


Estimated Enrollment: 170
Study Start Date: December 2011
Estimated Study Completion Date: January 2019
Estimated Primary Completion Date: January 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LGK974 Drug: LGK974

  Eligibility

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

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: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.

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

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

  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: NCT01351103

Locations
United States, Maryland
The Sidney Kimmel Cancer Center at Johns Hopkins Hospital Johns Hopkins
Baltimore, Maryland, United States, 21287-0013
United States, Massachusetts
Dana Farber Cancer Institute SC-7
Boston, Massachusetts, United States, 02215
United States, Michigan
University of Michigan Comprehensive Cancer Center Onc Dept.
Ann Arbor, Michigan, United States, 48109-0944
Karmanos Cancer Institute Wayne St
Detroit, Michigan, United States, 48201
United States, Texas
University of Texas/MD Anderson Cancer Center MD Anderson 2
Houston, Texas, United States, 77030-4009
Netherlands
Novartis Investigative Site
Rotterdam, Netherlands, 3075 EA
Spain
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08035
Novartis Investigative Site
Madrid, Spain, 28050
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01351103     History of Changes
Other Study ID Numbers: CLGK974X2101  2011-000495-33 
Study First Received: May 4, 2011
Last Updated: April 15, 2016
Health Authority: United States: Food and Drug Administration
Spain: MINSTERIO DE SANIDAD, POLÍTICA SOCIAL E IGUALDAD
Netherlands: Central Committee on Research inv. Human Subjects

Keywords provided by Novartis:
LGK974
pancreatic adenocarcinoma
BRAF mutant colorectal cancer
other tumor types with documented genetic alterations upstream in the Wnt signaling pathway
RNF43 mutation
RSPO fusion

Additional relevant MeSH terms:
Colorectal Neoplasms
Adenocarcinoma
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on December 09, 2016