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

May 7, 2012
April 11, 2014
September 2012
December 2014   (final data collection date for primary outcome measure)
Incidence rate of Dose Limiting Toxicities [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
Incidence of dose-limiting toxicities (DLTs)
Same as current
Complete list of historical versions of study NCT01602406 on ClinicalTrials.gov Archive Site
  • 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
Same as current
Not Provided
Not Provided
 
Phase I Study LJM716 Combined With Trastuzumab in Patients With HER2 Overexpressing Metastatic Breast or Gastric Cancer
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

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.

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Advanced HER2-positive Breast Cancer or Gastric Cancer
  • Drug: LJM716
  • Drug: Trastuzumab
Experimental: LJM716 in combination with trastuzumab
Interventions:
  • Drug: LJM716
  • Drug: Trastuzumab
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
65
December 2014
December 2014   (final data collection date for primary outcome measure)

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

Both
18 Years and older
No
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals
United States,   Italy,   Belgium,   France,   United Kingdom,   Korea, Republic of,   Netherlands,   Spain,   Taiwan
 
NCT01602406
CLJM716X2102, 2011-004881-13
Not Provided
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
April 2014

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