Advanced HER2-positive Breast Cancer or Gastric Cancer Clinical Trial
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
| Verified date | July 2018 |
| Source | Novartis |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 64 |
| Est. completion date | August 2, 2017 |
| Est. primary completion date | August 2, 2017 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| Belgium | Novartis Investigative Site | Wilrijk | |
| France | Novartis Investigative Site | Saint Herblain cedex | |
| Italy | Novartis Investigative Site | Milano | MI |
| Korea, Republic of | Novartis Investigative Site | Seoul | Korea |
| Netherlands | Novartis Investigative Site | Amsterdam | |
| Spain | Novartis Investigative Site | Valencia | Comunidad Valenciana |
| Taiwan | Novartis Investigative Site | Taipei | |
| United Kingdom | Novartis Investigative Site | Oxford | |
| United States | Novartis Investigative Site | Boston | Massachusetts |
| United States | Novartis Investigative Site | Chapel Hill | North Carolina |
| United States | Novartis Investigative Site | Philadelphia | Pennsylvania |
| Lead Sponsor | Collaborator |
|---|---|
| Novartis Pharmaceuticals |
United States, Belgium, France, Italy, Korea, Republic of, Netherlands, Spain, Taiwan, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Incidence rate of Dose Limiting Toxicities | Incidence of dose-limiting toxicities (DLTs) | 4 weeks | |
| Secondary | Number of adverse events | Safety assessment | 4 months | |
| Secondary | Number of serious adverse events | Safety assessment | 4 months | |
| Secondary | Pharmacodynamic response to LJM716 in tumor tissue | Post-treatment change from baseline in pHER3 levels in the tumor | 3 months | |
| Secondary | Progression-free survival | Efficacy assessment | 18 months | |
| Secondary | Duration of response | Efficacy assessment | 18 months | |
| Secondary | Serum concentration of anti-LJM716 antibodies | Incidence of antibodies against LJM716 | 4 months | |
| Secondary | Serum concentration of LJM716 when administered in combination with trastuzumab | PK profile | 4 months | |
| Secondary | Frequency of partial responses according to Response Evaluation Criteria In Solid Tumors (RECIST) | Efficacy assessment | every 2 months up to 18 months | |
| Secondary | Frequency of complete responses according to RECIST | Efficacy assessment | every 2 months up to 18 months | |
| Secondary | Frequency of stable disease according to RECIST | Efficacy assessment | every 2 months up to 18 months |