Overview

This trial is active, not recruiting.

Condition advanced her2-positive breast cancer or gastric cancer
Treatments ljm716, trastuzumab
Phase phase 1
Targets HER2, HER, HER3
Sponsor Novartis Pharmaceuticals
Start date September 2012
End date December 2016
Trial size 64 participants
Trial identifier NCT01602406, 2011-004881-13, CLJM716X2102

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
ljm716
trastuzumab

Primary Outcomes

Measure
Incidence rate of Dose Limiting Toxicities
time frame: 4 weeks

Secondary Outcomes

Measure
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

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

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
Trial information was received from ClinicalTrials.gov and was last updated in March 2016.
Information provided to ClinicalTrials.gov by Novartis.