Phase I Study LJM716 Combined With Trastuzumab in Patients With HER2 Overexpressing Metastatic Breast or Gastric Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01602406
First received: May 7, 2012
Last updated: April 11, 2014
Last verified: April 2014
  Purpose

This is a multicenter, open-label, dose escalation, phase I study to estimate the Maximum Tolerated Dose (MTD) or a lower Recommended Dose for Expansion (RDE) of LJM716 in combination with trastuzumab in patients with Human Epidermal growth factor Receptor 2 (HER2) overexpressing Metastatic Breast Cancer (MBC) or gastric cancer (MGC). The study consists of a dose escalation part and a dose expansion part. LJM716 will be administered intravenously once weekly unless a less frequent dosing regimen such as every 2 weeks or once every 4 weeks is introduced. Patients will continue on their trastuzumab dosing, administered intravenously once weekly at 2mg/kg. During dose escalation, a minimum of 15 patients are anticipated to be treated in successive cohorts. The dose escalation will continue until the MTD/RDE is declared. The RDE dose selected will either be the MTD or a dose below the MTD based on safety and Pharmacokinetic/Pharmacodynamic (PK/PD) considerations. Following the MTD/RDE declaration, approximately 20 MBC and 20 MGC patients will be enrolled in separate arms in the dose expansion part and treated at the MTD/RDE to further assess the safety, tolerability, and anti-tumor activity of the combination.


Condition Intervention Phase
Advanced HER2-positive Breast Cancer or Gastric Cancer
Drug: LJM716
Drug: Trastuzumab
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter, Open-label, Dose Escalation, Phase I Study of LJM716 Administered Intravenously in Combination With Trastuzumab in Patients With HER2 Overexpressing Metastatic Breast Cancer or Gastric Cancer

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Incidence rate of Dose Limiting Toxicities [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
    Incidence of dose-limiting toxicities (DLTs)


Secondary Outcome Measures:
  • Number of adverse events [ Time Frame: 4 months ] [ Designated as safety issue: Yes ]
    Safety assessment

  • Number of serious adverse events [ Time Frame: 4 months ] [ Designated as safety issue: Yes ]
    Safety assessment

  • Pharmacodynamic response to LJM716 in tumor tissue [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Post-treatment change from baseline in pHER3 levels in the tumor

  • Progression-free survival [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Efficacy assessment

  • Duration of response [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Efficacy assessment

  • Serum concentration of anti-LJM716 antibodies [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    Incidence of antibodies against LJM716

  • Serum concentration of LJM716 when administered in combination with trastuzumab [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    PK profile

  • Frequency of partial responses according to Response Evaluation Criteria In Solid Tumors (RECIST) [ Time Frame: every 2 months up to 18 months ] [ Designated as safety issue: No ]
    Efficacy assessment

  • Frequency of complete responses according to RECIST [ Time Frame: every 2 months up to 18 months ] [ Designated as safety issue: No ]
    Efficacy assessment

  • Frequency of stable disease according to RECIST [ Time Frame: every 2 months up to 18 months ] [ Designated as safety issue: No ]
    Efficacy assessment


Estimated Enrollment: 65
Study Start Date: September 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LJM716 in combination with trastuzumab Drug: LJM716 Drug: Trastuzumab

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with confirmed HER-2 positive, metastatic or non-operable locally advanced breast or gastric cancer
  • Metastatic breast cancer patients must have received a minimum of 1 and a maximum of 3 prior anti HER2 based regimens with documented progression on the most recent regimen which must contain trastuzumab, ado-trastuzumab emtansine or lapatinib
  • Metastatic gastric cancer patients must have received a minimum of 1 and a maximum of 2 prior anti HER2 based regimens with documented progression on the most recent regimen which must contain trastuzumab or ado-trastuzumab emtansine
  • During the dose expansion part of study, all patients must have at least one measurable lesion as defined by RECIST criteria.
  • Patients must have at least one prior trastuzumab-containing regimen
  • Eastern Cooperative Oncology Group (ECOG) Performance status ≤ 2

Exclusion Criteria:

  • Patients with Central Nervous System (CNS) metastasis which are: symptomatic or require treatment for symptom control and/or growing
  • Prior treatment with any anti-HER3 (Human Epidermal growth factor Receptor 3) treatment
  • Impaired cardiac function
  • Prior to the first dose of study treatment, patients who have received systemic antineoplastic therapy or any investigational therapy within 4 weeks or within 5 half- lives of the therapy prior to starting study treatment, whichever is shorter, or for cyclical therapy, within one cycle length (e.g. 6 weeks for nitrosourea, mitomycin-C).
  • Patients who have a history of primary malignancy other than that being treated in this study, and currently requires active clinical intervention.
  • Patients who do not have an archival tumor sample (or sections of it) available or readily obtainable.

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: NCT01602406

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

Locations
United States, Massachusetts
Massachusetts General Hospital SC-5 Recruiting
Boston, Massachusetts, United States, 02114
Contact: Sarah Farooq       sfarooq@partners.org   
Principal Investigator: Dejan Juric         
United States, North Carolina
University of North Carolina UNC 2 Recruiting
Chapel Hill, North Carolina, United States, 27514
Contact: Bethany Whitsell    +1 919 966 4432    bethany_whitsell@med.unc.edu   
Principal Investigator: E Claire Dees         
Duke University Medical Center SC Recruiting
Durham, North Carolina, United States, 27710
Contact: Marla Jordan    919-660-1278    dcccsafe@dm.duke.edu   
Principal Investigator: Kimberly Blackwell         
United States, Pennsylvania
Fox Chase Cancer Center FCC 2 Recruiting
Philadelphia, Pennsylvania, United States, 19111-2497
Contact: Joanne Ley    215-728-2689    Joanne.ley@fccc.edu   
Principal Investigator: Lori Goldstein         
Belgium
Novartis Investigative Site Recruiting
Wilrijk, Belgium, 2610
France
Novartis Investigative Site Withdrawn
Montpellier Cedex 5, France, 34298
Novartis Investigative Site Terminated
Saint Herblain cedex, France, 44805
Italy
Novartis Investigative Site Recruiting
Milano, MI, Italy, 20133
Novartis Investigative Site Recruiting
Rozzano, MI, Italy, 20089
Korea, Republic of
Novartis Investigative Site Recruiting
Seoul, Korea, Korea, Republic of, 110 744
Netherlands
Novartis Investigative Site Recruiting
Amsterdam, Netherlands, 1066 CX
Spain
Novartis Investigative Site Recruiting
Valencia, Comunidad Valenciana, Spain, 46010
Taiwan
Novartis Investigative Site Recruiting
Taipei, Taiwan, 10002
United Kingdom
Novartis Investigative Site Recruiting
Oxford, United Kingdom, OX3 7LJ
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: NCT01602406     History of Changes
Other Study ID Numbers: CLJM716X2102, 2011-004881-13
Study First Received: May 7, 2012
Last Updated: April 11, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
Advanced HER2-positive Breast cancer or Gastric cancer

Additional relevant MeSH terms:
Breast Neoplasms
Stomach Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Trastuzumab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014