Advanced HER2-positive Breast Cancer or Gastric CancerPhase 1NCT01602406
Phase I Study LJM716 Combined With Trastuzumab in Patients With HER2 Overexpressing Metastatic Breast or Gastric Cancer
A Phase 1 study testing LJM716 and Trastuzumab in people with Advanced HER2-positive Breast Cancer or Gastric Cancer, run by Novartis Pharmaceuticals at 11 sites in 9 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced HER2-positive Breast Cancer or Gastric Cancer
- What is being tested?
- LJM716 and Trastuzumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 64 participants
- Where
- 11 sitesin 9 countries
- Study dates
- 21 Sep 2012to 2 Aug 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
11 sites in 9 countries.
11 sites in 9 countries
United States3 sites
Novartis Investigative Site
Boston, Massachusetts, 02114
Novartis Investigative Site
Chapel Hill, North Carolina, 27514
Novartis Investigative Site
Philadelphia, Pennsylvania, 19111
About this study
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
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.
- Being tested
- LJM716, Trastuzumab
- Keywords
- Advanced HER2-positive Breast cancer or Gastric cancer
- Medical subject headings
- Stomach Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LJM716Drug
LJM716
TrastuzumabDrug
Trastuzumab
| Study group | Role | What they receive |
|---|---|---|
| LJM716 in combination with trastuzumab | Experimental | Not described Receives: Drug: LJM716; Drug: Trastuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence rate of Dose Limiting Toxicities
Incidence of dose-limiting toxicities (DLTs)
Measured: 4 weeks
Secondary outcomes (10)
Number of adverse events
Safety assessment
Measured: 4 months
Number of serious adverse events
Safety assessment
Measured: 4 months
Pharmacodynamic response to LJM716 in tumor tissue
Post-treatment change from baseline in pHER3 levels in the tumor
Measured: 3 months
Progression-free survival
Efficacy assessment
Measured: 18 months
Duration of response
Efficacy assessment
Measured: 18 months
Serum concentration of anti-LJM716 antibodies
Incidence of antibodies against LJM716
Measured: 4 months
Serum concentration of LJM716 when administered in combination with trastuzumab
PK profile
Measured: 4 months
Frequency of partial responses according to Response Evaluation Criteria In Solid Tumors (RECIST)
Efficacy assessment
Measured: every 2 months up to 18 months
Frequency of complete responses according to RECIST
Efficacy assessment
Measured: every 2 months up to 18 months
Frequency of stable disease according to RECIST
Efficacy assessment
Measured: every 2 months up to 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2012 (estimated)
- Study start21 Sep 2012
- Primary completion2 Aug 2017
- Study completion2 Aug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced HER2-positive Breast Cancer or Gastric CancerStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01602406
- Sponsor's protocol ID
- CLJM716X2102
- Other IDs
- 2011-004881-13
- Status last verified
- Jul 2018
- First submitted
- 7 May 2012
- Last updated
- 19 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01602406
- Acronym / sponsor ID
- CLJM716X2102
- Keywords
- Advanced HER2-positive Breast cancer or Gastric cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 21 Sep 2012 (actual)
- Primary completion
- 2 Aug 2017 (actual)
- Study completion
- 2 Aug 2017 (actual)
- First posted
- 21 May 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| LJM716 in combination with trastuzumab | Experimental | Drug: LJM716, Drug: Trastuzumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LJM716LJM716 | Drug | LJM716 in combination with trastuzumab |
| TrastuzumabTrastuzumab | Drug | LJM716 in combination with trastuzumab |
Primary outcome
Incidence rate of Dose Limiting Toxicities
Time frame: 4 weeks
Incidence of dose-limiting toxicities (DLTs)
10 secondary outcomes
Number of adverse events
Time frame: 4 months
Number of serious adverse events
Time frame: 4 months
Pharmacodynamic response to LJM716 in tumor tissue
Time frame: 3 months
Progression-free survival
Time frame: 18 months
Duration of response
Time frame: 18 months
Serum concentration of anti-LJM716 antibodies
Time frame: 4 months
Serum concentration of LJM716 when administered in combination with trastuzumab
Time frame: 4 months
Frequency of partial responses according to Response Evaluation Criteria In Solid Tumors (RECIST)
Time frame: every 2 months up to 18 months
Frequency of complete responses according to RECIST
Time frame: every 2 months up to 18 months
Frequency of stable disease according to RECIST
Time frame: every 2 months up to 18 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2020.
- Results for CLJM716X2102 from the Novartis Clinical Trials WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
11 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing LJM716 and Trastuzumab in people with Advanced HER2-positive Breast Cancer or Gastric Cancer, run by Novartis Pharmaceuticals at 11 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States, Belgium, France, Italy, Netherlands and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence rate of Dose Limiting Toxicities (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2020.