Clinical trial NCT01602406: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced HER2-positive Breast Cancer or Gastric Cancer
Keywords: Advanced HER2-positive Breast cancer or Gastric cancer
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-05-21
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Incidence rate of Dose Limiting Toxicities
timeFrame: 4 weeks
Secondary outcomes:
measure: Number of adverse events
timeFrame: 4 months
measure: Number of serious adverse events
timeFrame: 4 months
measure: Pharmacodynamic response to LJM716 in tumor tissue
timeFrame: 3 months
measure: Progression-free survival
timeFrame: 18 months
measure: Duration of response
timeFrame: 18 months
measure: Serum concentration of anti-LJM716 antibodies
timeFrame: 4 months
measure: Serum concentration of LJM716 when administered in combination with trastuzumab
timeFrame: 4 months
measure: Frequency of partial responses according to Response Evaluation Criteria In Solid Tumors (RECIST)
timeFrame: every 2 months up to 18 months
measure: Frequency of complete responses according to RECIST
timeFrame: every 2 months up to 18 months
measure: Frequency of stable disease according to RECIST
timeFrame: every 2 months up to 18 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: Chapel Hill
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Philadelphia
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
city: Wilrijk
country: Belgium
facility: Novartis Investigative Site
city: Saint Herblain cedex
country: France
facility: Novartis Investigative Site
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Amsterdam
country: Netherlands
facility: Novartis Investigative Site
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Oxford
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: