- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01602406
Phase I Study LJM716 Combined With Trastuzumab in Patients With HER2 Overexpressing Metastatic Breast or Gastric Cancer
December 16, 2020 updated by: Novartis Pharmaceuticals
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.
Study Overview
Status
Completed
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
64
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Wilrijk, Belgium, 2610
- Novartis Investigative Site
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Saint Herblain cedex, France, 44805
- Novartis Investigative Site
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MI
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Milano, MI, Italy, 20133
- Novartis Investigative Site
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Korea
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Seoul, Korea, Korea, Republic of, 03080
- Novartis Investigative Site
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Amsterdam, Netherlands, 1066 CX
- Novartis Investigative Site
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Comunidad Valenciana
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Valencia, Comunidad Valenciana, Spain, 46010
- Novartis Investigative Site
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Taipei, Taiwan, 10002
- Novartis Investigative Site
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Oxford, United Kingdom, OX3 7LJ
- Novartis Investigative Site
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Massachusetts
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Boston, Massachusetts, United States, 02114
- Novartis Investigative Site
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North Carolina
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Chapel Hill, North Carolina, United States, 27514
- Novartis Investigative Site
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19111
- Novartis Investigative Site
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: LJM716 in combination with trastuzumab
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LJM716
Trastuzumab
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Incidence rate of Dose Limiting Toxicities
Time Frame: 4 weeks
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Incidence of dose-limiting toxicities (DLTs)
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4 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Number of adverse events
Time Frame: 4 months
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Safety assessment
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4 months
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Number of serious adverse events
Time Frame: 4 months
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Safety assessment
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4 months
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Pharmacodynamic response to LJM716 in tumor tissue
Time Frame: 3 months
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Post-treatment change from baseline in pHER3 levels in the tumor
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3 months
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Progression-free survival
Time Frame: 18 months
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Efficacy assessment
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18 months
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Duration of response
Time Frame: 18 months
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Efficacy assessment
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18 months
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Serum concentration of anti-LJM716 antibodies
Time Frame: 4 months
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Incidence of antibodies against LJM716
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4 months
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Serum concentration of LJM716 when administered in combination with trastuzumab
Time Frame: 4 months
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PK profile
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4 months
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Frequency of partial responses according to Response Evaluation Criteria In Solid Tumors (RECIST)
Time Frame: every 2 months up to 18 months
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Efficacy assessment
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every 2 months up to 18 months
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Frequency of complete responses according to RECIST
Time Frame: every 2 months up to 18 months
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Efficacy assessment
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every 2 months up to 18 months
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Frequency of stable disease according to RECIST
Time Frame: every 2 months up to 18 months
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Efficacy assessment
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every 2 months up to 18 months
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
September 21, 2012
Primary Completion (Actual)
August 2, 2017
Study Completion (Actual)
August 2, 2017
Study Registration Dates
First Submitted
May 7, 2012
First Submitted That Met QC Criteria
May 18, 2012
First Posted (Estimate)
May 21, 2012
Study Record Updates
Last Update Posted (Actual)
December 19, 2020
Last Update Submitted That Met QC Criteria
December 16, 2020
Last Verified
July 1, 2018
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CLJM716X2102
- 2011-004881-13 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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