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

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ClinicalTrials.gov Identifier: NCT01351103
Recruitment Status : Recruiting
First Posted : May 10, 2011
Last Update Posted : December 11, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE May 4, 2011
First Posted Date  ICMJE May 10, 2011
Last Update Posted Date December 11, 2018
Actual Study Start Date  ICMJE December 1, 2011
Estimated Primary Completion Date March 18, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 24, 2017)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: May 9, 2011)
Maximum Tolerated Dose of LGK974 in patients treated daily [ Time Frame: 12 months ]
Change History Complete list of historical versions of study NCT01351103 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 16, 2018)
  • 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 Overall Response Rate(ORR), complete response (CR) or partial response (PR) rate and duration of response (DOR) assessed by RECIST 1.1 for single agent LGK974 and by RECIST1.1 and irRC for LGK974+PDR001.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 9, 2011)
  • 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of LGK974 in Patients With Malignancies Dependent on Wnt Ligands
Official Title  ICMJE A Phase I, Open-label, Dose Escalation Study of Oral LGK974 in Patients With Malignancies Dependent on Wnt Ligands
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Pancreatic Cancer
  • BRAF Mutant Colorectal Cancer
  • Melanoma
  • Triple Negative Breast Cancer
  • Head and Neck Squamous Cell Cancer
  • Cervical Squamous Cell Cancer
  • Esophageal Squamous Cell Cancer
  • Lung Squamous Cell Cancer
Intervention  ICMJE
  • Drug: LGK974
    Other Name: WNT974
  • Biological: PDR001
Study Arms  ICMJE
  • Experimental: LGK974
    Intervention: Drug: LGK974
  • Experimental: LGK974 in combination with PDR001
    Interventions:
    • Drug: LGK974
    • Biological: PDR001
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 23, 2016)
170
Original Estimated Enrollment  ICMJE
 (submitted: May 9, 2011)
50
Estimated Study Completion Date  ICMJE August 20, 2020
Estimated Primary Completion Date March 18, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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: patients with the following cancers that were previously treated with anti-PD-1 therapy and whose best response on that therapy was progressive disease (i.e. primary refractory): melanoma, lung SCC, HNSCC. Patients with esophageal SCC, cervical SCC or TNBC who are either naïve or primary refractory to prior anti-PD-1 therapy.

LGK974 with PDR001: 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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Novartis Pharmaceuticals 1-888-669-6682 Novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111
Listed Location Countries  ICMJE Netherlands,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01351103
Other Study ID Numbers  ICMJE CLGK974X2101
2011-000495-33 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date December 2018

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