Phase 1
N=15
T-DM1 and Non-pegylated Liposomal Doxorubicin in Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Breast Cancer
Breast Cancer
Bottom Line
View on ClinicalTrials.gov: NCT02562378 ↗Enrolled (actual)
15
Serious AEs
13.3%
Results posted
Jan 2022
Primary outcome: Primary: Hematological - Dose Limiting Toxicities — 1; 3; 7; 1 participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Trastuzumab and non-pegylated liposomal doxorubicin (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- MedSIR
- Primary completion
- Dec 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Hematological - Dose Limiting Toxicities |
1; 3; 7; 1; 2; 6 | — |
| PRIMARY Non-Hematological - Dose Limiting Toxicities |
3; 2; 4; 2; 3; 4 | — |
| SECONDARY Overall Response Rate |
33.3; 66.7; 33.3 | — |
| SECONDARY Best Overall Response |
1; 2; 3; 1; 0; 3 | — |
| SECONDARY Clinical Benefit Rate |
66.7; 66.7; 66.7 | — |
| SECONDARY Progression-free Survival |
8.2; 7.0; 7.2 | — |
| SECONDARY Grade 3/4 Adverse Events, SAEs, Deaths and Discontinuations |
0; 2; 6; 0; 0; 2 | — |
| SECONDARY Discontinuation of the Study Drugs Due to Any Cardiotoxicity |
0; 0; 0 | — |
| SECONDARY Left Ventricular Dysfunction Class IV |
0; 1; 2 | — |
| SECONDARY Serum HER-2 Levels |
12.7; 38.1; 17.5; 7.4; 15.2; 18.8 | — |
| SECONDARY Doxorubicinol - Concentration (Cmax) |
14.8; 9.19; 15.2; 16.0; 10.1; 15.6 | — |
| SECONDARY Doxorubicinol - Area Under Curve (AUC) |
982; 888; 1340; 899; 763; 1100 | — |
| SECONDARY Doxorubicinol - Apparent Half-life (t1/2) |
93.4; 78.5; 69.3; 51.91; 64.01; 49.41 | — |
| SECONDARY Doxorubicinol - Tmax |
3.75; 3.58; 3.63; 4.02; 3.58; 3.78 | — |
| SECONDARY Trastuzumab - Cmax |
94.6; 114; 78.3 | — |
| SECONDARY Trastuzumab - AUC |
348; 372; 317 | — |
| SECONDARY Trastuzumab - Tmax |
1.95; 1.83; 1.95 | — |
| SECONDARY DM-1 - Cmax |
3.76; 8.03; 5.13 | — |
| SECONDARY DM-1 - AUC |
23.1; 10.1; 5.63 | — |
| SECONDARY DM-1 - Tmax |
2.0; 1.83; 1.95 | — |
Summary
The primary goal is to determine the maximum tolerated dose (MTD) of the combination of T-DM1 and non-pegylated liposomal doxorubicin in metastatic breast cancer (mBC) patients previously treated with taxanes and trastuzumab-based therapy.
In addition, pharmacokinetic data on the combination of T-DM1 and liposomal doxorubicin will be obtained.
Eligibility Criteria
Inclusion Criteria
- Signed informed consent
- Patient able and willing to comply with protocol
- Cytologically or histologically confirmed carcinoma of the breast.
- Incurable locally advanced or metastatic disease who have previously received up to two previous chemotherapy regimens in this setting. Patient must have progressed or relapsed on or after taxane and trastuzumab-based therapy.
- HER2-positive disease
- At least one measurable lesion according to RECIST version 1.1; or patients with non measurable lesions could be included with these exceptions:
o patients with only blastic bone lesions / with only pleural, peritoneal or cardiac effusion, or meningeal carcinomatosis
- ≥ 18 years of age
- Eastern Cooperative Oncology Group (ECOG) 0 or 1
- Life expectancy ≥ 3 months
- Adequate bone marrow function:
- Hemoglobin ≥ 10 g/dl.
- Absolute neutrophil count ≥ 1.5 x 109/L.
- Platelets ≥ 100 x 109/L without transfusions within 21 days
- International normalized ratio (INR) 4 weeks from radiotherapy completion, is clinically stable with respect to CNS tumor at the time of study entry and is not receiving steroid therapy for brain metastases
- Severe/uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.
- Cardiopulmonary dysfunction
- Current peripheral neuropathy of Grade ≥ 3 per the NCI CTCAE, v4.0
- History of a decrease in LVEF to < 40% or symptomatic congestive heart failure (CHF) with previous trastuzumab treatment
- Prior malignancy, other than carcinoma in situ of the cervix, or non-melanoma skin cancer, unless the prior malignancy was cured ≥ 5 years before first dose of study drug with no subsequent evidence of recurrence
- Current known active infection with HIV, hepatitis B, and/or hepatitis C virus
- Women who are pregnant or breast-feeding
Data sourced from ClinicalTrials.gov (NCT02562378). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.