Phase I Study LJM716 Combined With Trastuzumab in Patients With HER2 Overexpressing Metastatic Breast or Gastric Cancer
Primary Purpose
Advanced HER2-positive Breast Cancer or Gastric Cancer
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
LJM716
Trastuzumab
Sponsored by
About this trial
This is an interventional treatment trial for Advanced HER2-positive Breast Cancer or Gastric Cancer focused on measuring Advanced HER2-positive Breast cancer or Gastric cancer
Eligibility 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
Sites / Locations
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
LJM716 in combination with trastuzumab
Arm Description
Outcomes
Primary Outcome Measures
Incidence rate of Dose Limiting Toxicities
Incidence of dose-limiting toxicities (DLTs)
Secondary Outcome Measures
Number of adverse events
Safety assessment
Number of serious adverse events
Safety assessment
Pharmacodynamic response to LJM716 in tumor tissue
Post-treatment change from baseline in pHER3 levels in the tumor
Progression-free survival
Efficacy assessment
Duration of response
Efficacy assessment
Serum concentration of anti-LJM716 antibodies
Incidence of antibodies against LJM716
Serum concentration of LJM716 when administered in combination with trastuzumab
PK profile
Frequency of partial responses according to Response Evaluation Criteria In Solid Tumors (RECIST)
Efficacy assessment
Frequency of complete responses according to RECIST
Efficacy assessment
Frequency of stable disease according to RECIST
Efficacy assessment
Full Information
NCT ID
NCT01602406
First Posted
May 7, 2012
Last Updated
December 16, 2020
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT01602406
Brief Title
Phase I Study LJM716 Combined With Trastuzumab in Patients With HER2 Overexpressing Metastatic Breast or Gastric Cancer
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2018
Overall Recruitment Status
Completed
Study Start Date
September 21, 2012 (Actual)
Primary Completion Date
August 2, 2017 (Actual)
Study Completion Date
August 2, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced HER2-positive Breast Cancer or Gastric Cancer
Keywords
Advanced HER2-positive Breast cancer or Gastric cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
64 (Actual)
8. Arms, Groups, and Interventions
Arm Title
LJM716 in combination with trastuzumab
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
LJM716
Intervention Description
LJM716
Intervention Type
Drug
Intervention Name(s)
Trastuzumab
Intervention Description
Trastuzumab
Primary Outcome Measure Information:
Title
Incidence rate of Dose Limiting Toxicities
Description
Incidence of dose-limiting toxicities (DLTs)
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
Number of adverse events
Description
Safety assessment
Time Frame
4 months
Title
Number of serious adverse events
Description
Safety assessment
Time Frame
4 months
Title
Pharmacodynamic response to LJM716 in tumor tissue
Description
Post-treatment change from baseline in pHER3 levels in the tumor
Time Frame
3 months
Title
Progression-free survival
Description
Efficacy assessment
Time Frame
18 months
Title
Duration of response
Description
Efficacy assessment
Time Frame
18 months
Title
Serum concentration of anti-LJM716 antibodies
Description
Incidence of antibodies against LJM716
Time Frame
4 months
Title
Serum concentration of LJM716 when administered in combination with trastuzumab
Description
PK profile
Time Frame
4 months
Title
Frequency of partial responses according to Response Evaluation Criteria In Solid Tumors (RECIST)
Description
Efficacy assessment
Time Frame
every 2 months up to 18 months
Title
Frequency of complete responses according to RECIST
Description
Efficacy assessment
Time Frame
every 2 months up to 18 months
Title
Frequency of stable disease according to RECIST
Description
Efficacy assessment
Time Frame
every 2 months up to 18 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Novartis Investigative Site
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27514
Country
United States
Facility Name
Novartis Investigative Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
Facility Name
Novartis Investigative Site
City
Wilrijk
ZIP/Postal Code
2610
Country
Belgium
Facility Name
Novartis Investigative Site
City
Saint Herblain cedex
ZIP/Postal Code
44805
Country
France
Facility Name
Novartis Investigative Site
City
Milano
State/Province
MI
ZIP/Postal Code
20133
Country
Italy
Facility Name
Novartis Investigative Site
City
Seoul
State/Province
Korea
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Amsterdam
ZIP/Postal Code
1066 CX
Country
Netherlands
Facility Name
Novartis Investigative Site
City
Valencia
State/Province
Comunidad Valenciana
ZIP/Postal Code
46010
Country
Spain
Facility Name
Novartis Investigative Site
City
Taipei
ZIP/Postal Code
10002
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Oxford
ZIP/Postal Code
OX3 7LJ
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17162
Description
Results for CLJM716X2102 from the Novartis Clinical Trials Website
Learn more about this trial
Phase I Study LJM716 Combined With Trastuzumab in Patients With HER2 Overexpressing Metastatic Breast or Gastric Cancer
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