Clinical Trial - NCT01351103

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

Recruiting

Sponsor: Novartis Pharmaceuticals

Collaborators:

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT01351103

Protocol Info

Short Description: Phase I of LGK974 in Malignancies Dependent on Wnt ligands
Long Description: A Phase I, Open-label, Dose Escalation Study of Oral LGK974 in Patients With Malignancies Dependent on Wnt Ligands
MGH Status: Open
Sponsor: Novartis
Disease Program: Phase I

Next Steps


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Purpose

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.
Condition Title Intervention Phase
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 LGK974 PDR001 Phase 1
Study Type Interventional
Official Title A Phase I, Open-label, Dose Escalation Study of Oral LGK974 in Patients With Malignancies Dependent on Wnt Ligands

Primary Outcome Measures

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] [Designated as safety issue: ]


Secondary Outcome Measures

Type and category of study drug related adverse events (AE) [Time Frame: 61 months] [Designated as safety issue: ]

Absorption and plasma concentrations of LGK974 [Time Frame: 61 months] [Designated as safety issue: ]

Biomarkers related to the Wnt pathway [Time Frame: 61 months] [Designated as safety issue: ]

Overall response rate of tumor [Time Frame: 61 months] [Designated as safety issue: ]

Absorportion and plasma concentrations of PDR001 [Time Frame: 61 months] [Designated as safety issue: ]

Biomarkers related to immunomodulation [Time Frame: 61 months] [Designated as safety issue: ]

Estimated Enrollment: 170
Study Start Date: December 2011
Estimated Study Completion Date: August 2020
Estimated Primary Completion Date: March 2020
Arms Assigned Interventions

Experimental:LGK974

Drug:LGK974

Experimental:LGK974 in combination with PDR001

Biological:PDR001

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01351103

Locations

  • United States, California
    • Novartis Investigative Site Los Angeles, California, United States, 90024
  • United States, Maryland
    • Novartis Investigative Site Baltimore, Maryland, United States, 21287-0013
  • United States, Massachusetts
    • Dana Farber Cancer Institute SC Boston, Massachusetts, United States, 02115
    • 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
    • Novartis Investigative Site Utrecht, , Netherlands, 3584CX
  • Spain, Catalunya
    • Novartis Investigative Site Barcelona, Catalunya, Spain, 08035
    • Novartis Investigative Site Barcelona, Catalunya, Spain, 08036
  • Spain,
    • Novartis Investigative Site Madrid, , Spain, 28007
    • Novartis Investigative Site Madrid, , Spain, 28050

Sponsors and Collaborators

Novartis Pharmaceuticals

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT01351103
Other Study ID Numbers: 2011-000495-33
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Novartis:

LGK974

pancreatic adenocarcinoma

BRAF mutant colorectal cancer

RNF43 mutation

RSPO fusion

melanoma

triple negative breast cancer

PDR001

immunotherapy

head and neck scc

cervical scc

esophageal scc

lung scc

Additional relevant MeSH terms:

Melanoma

Colorectal Neoplasms

Pancreatic Neoplasms

Triple Negative Breast Neoplasms

Neoplasms, Squamous Cell

Carcinoma, Squamous Cell

Esophageal Squamous Cell Carcinoma

LGK974

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on August 15, 2019