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
  Purpose

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.


Condition Intervention Phase
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
Phase 1

Study Type: Interventional
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

Resource links provided by NLM:


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: 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 80
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)
Arms Assigned Interventions
Experimental: LGK974 Drug: LGK974

  Eligibility

Ages Eligible for Study:   18 Years and older
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: 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

  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

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals

Locations
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    aoconnor@jhmi.edu   
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    brewert@karmanos.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    vstepane@mdanderson.org   
Principal Investigator: Sapna Pradyuman Patel         
Netherlands
Novartis Investigative Site Recruiting
Rotterdam, Netherlands, 3075 EA
Spain
Novartis Investigative Site Recruiting
Barcelona, Cataluña, Spain, 08035
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( 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: March 31, 2014
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
Melanoma
Breast neoplasms
lobular carcinoma
triple-negative breast cancer
pancreatic adenocarcinoma
colorectal cancer
head and neck cancer
head and neck squamous cell carcinoma
other tumor types with documented genetic alterations upstream in the Wnt signaling pathway

Additional relevant MeSH terms:
Neoplasms
Melanoma
Colorectal Neoplasms
Adenocarcinoma
Head and Neck Neoplasms
Breast Neoplasms
Carcinoma
Triple Negative Breast Neoplasms
Carcinoma, Lobular
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplasms, Glandular and Epithelial
Breast Diseases
Skin Diseases
Neoplasms, Ductal, Lobular, and Medullary

ClinicalTrials.gov processed this record on September 29, 2014