Phase I Study LJM716 Combined With Trastuzumab in Patients With HER2 Overexpressing Metastatic Breast or Gastric Cancer
| Status: | Completed |
|---|---|
| Conditions: | Breast Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 7/28/2018 |
| Start Date: | September 21, 2012 |
| End Date: | August 2, 2017 |
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.
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.
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
We found this trial at
4
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