Phase 2
Completed N=63
A Study of Trastuzumab Emtansine, Paclitaxel, and Pertuzumab in Patients With HER2-Positive, Locally Advanced or Metastatic Breast Cancer
Source: ClinicalTrials.gov NCT00951665 ↗Enrolled (actual)
63
Serious AEs
31.7%
Results posted
Jun 2016
Primary outcomePrimary: Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (SAEs), AEs of Grades 3/4, and Death — 26; 10; 21; 3 participants
Summary
This Phase Ib-IIa, multi-institutional, open-label, dose-escalation study is designed to evaluate the safety, tolerability, pharmacokinetics and feasibility of trastuzumab emtansine (T-DM1) administered by intravenous (IV) infusion in combination with paclitaxel (and pertuzumab, if applicable) in patients with human epidermal growth factor receptor 2-positive (HER2-positive), locally advanced or metastatic breast cancer.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (SAEs), AEs of Grades 3/4, and Death |
26; 10; 21; 3; 22; 22 | — |
| PRIMARY Number of Participants With Dose Limiting Toxicity (DLT) of the Combination of T-DM1 and Paclitaxel When T-DM1 Was Administered on Either an Q3W or QW Schedule for Both With and Without Pertuzumab Treatment |
0; 0; 0; 0 | — |
| PRIMARY Maximum Tolerated Dose of T-DM1 When T-DM1 (Q3W or QW) and Paclitaxel (QW) Was Administered With and Without Pertuzumab |
3.6; 3.6; 2.4; 2.4 | — |
| PRIMARY Maximum Tolerated Dose of Paclitaxel When T-DM1 (Q3W or QW) and Paclitaxel (QW) Was Administered With and Without Pertuzumab |
80; 80; 80; 80 | — |
| PRIMARY Number of Participants in Phase IIa of the Study Who Received 12 or More Paclitaxel Doses in Combination With T-DM1 and/or Pertuzumab |
11; 11 | — |
| PRIMARY Number of Participants Who Had Adverse Events That Required Dose Modification of T-DM1 or Paclitaxel |
13; 5; 19; 2; 15; 12 | — |
| PRIMARY Maximum Serum Concentration (Cmax) of T-DM1 and Total Trastuzumab in Cycle 1 After Q3W Dose Regimen |
53.5; 44.9; 43.6; 54.6; 62.2; 76.1 | — |
| PRIMARY Maximum Plasma Concentration (Cmax) of DM1 in Cycle 1 After Q3W Dose Regimen |
2.4; 3.4; 2.7; 3.2; 5.1 | — |
| PRIMARY Area Under the Serum Concentration-time Curve of Total Exposure (AUC0-Day 21) of T-DM1 and Total Trastuzumab in Cycle 1 After Q3W Dose Regimen |
241; 216; 264; 271; 382; 523 | — |
| PRIMARY Maximum Serum Concentration (Cmax) of T-DM1 and Total Trastuzumab in Cycle 1 After QW Dose Regimen |
24.3; 26; 39.4; 63.7; 87.8; 57.8 | — |
| PRIMARY Maximum Plasma Concentration (Cmax) of DM1 in Cycle 1 After QW Dose Regimen |
1.0; 1.8; 3.0; 2.7; 4.0 | — |
| PRIMARY Area Under the Serum Concentration-time Curve of Total Exposure (AUClast) of T-DM1 and Total Trastuzumab in Cycle 1 After QW Dose Regimen |
84.6; 91.9; 150; 242; 165; 275 | — |
| PRIMARY Maximum Plasma Concentration of Paclitaxel in Cycle 1 (in the Absence T-DM1) and Cycle 2 (in the Presence T-DM1) |
1430; 1280; 1540; 1590 | — |
| PRIMARY Area Under Plasma Concentration - Time Curve of Paclitaxel From Time 0 to Infinity (AUC0-inf) in Cycle 1 (in the Absence of T-DM1) and Cycle 2 (in the Presence of T-DM1) |
3440; 3520; 3890; 4220 | — |
| PRIMARY An Elimination Half-life (t1/2) of Plasma Concentration of Paclitaxel in Cycle 1 (in the Absence of T-DM1) and Cycle 2 (in the Presence of T-DM1) |
9.89; 11.7; 8.94; 10.8 | — |
| PRIMARY Plasma Clearance (CL) of Concentration of Paclitaxel in Cycle 1 (in the Absence of T-DM1) and Cycle 2 (in the Presence of T-DM1) |
20.7; 21; 22.8; 23 | — |
| PRIMARY An Apparent Volume of Distribution at Steady-state (Vss) of Plasma Concentration of Paclitaxel in Cycle 1 (in the Absence of T-DM1) and Cycle 2 (in the Presence of T-DM1) |
167; 220; 166; 196 | — |
| PRIMARY Number of Participants With Change From Baseline in Cardiac Function |
8; 3; 5; 0; 5; 4 | — |
| SECONDARY Percentage of Participants With Objective Response Rate (ORR) |
50.0; 70.0; 50.0; 66.7; 47.6; 52.4 | — |
| SECONDARY Duration of Objective Response |
7.1; NA; 7.0; NA; NA; NA | — |
| SECONDARY Percentage of Participants With Clinical Benefit |
65.4; 80.0; 61.9; 66.7; 54.5; 59.1 | — |
| SECONDARY Progression-free Survival (PFS) |
11.7; 11.9; 11.3; 11.0; 6.0; 6.6 | — |
Eligibility Criteria
Inclusion Criteria
- Histologically documented HER2-positive locally advanced or metastatic breast cancer
- Tumor tissue blocks or 15-20 unstained tissue slides for confirmatory central laboratory HER2 status testing and other exploratory assessments
- Prior trastuzumab in any line of therapy (Phase Ib patients only)
- No prior T-DM1 or pertuzumab therapy
- Measurable or evaluable disease
- Cardiac ejection fraction >=50% by either echocardiogram or multigated acquisition scan
- Life expectancy >= 90 days as assessed by the investigator
Exclusion Criteria
- Fewer than 21 days since the last anti-tumor therapy, including chemotherapy, biologic, experimental, immune, hormonal or radiotherapy for the treatment of breast cancer, with the following exceptions: hormone-replacement therapy or oral contraceptives are allowed; palliative radiation therapy involving = 14 days prior to first study treatment
- History of intolerance or hypersensitivity to trastuzumab and/or adverse events related to trastuzumab, murine proteins, or any of the excipients that resulted in trastuzumab being permanently discontinued
- Peripheral neuropathy of Grade >= 2 per NCI CTCAE, Version 3.0, at the time of, or within 3 weeks prior to, the first study therapy (Phase Ib patients)
- Peripheral neuropathy of Grade >/=1 per NCI CTCAE, Version 3.0, at the time of, or within 3 weeks prior to, the first study therapy (Phase IIa patients)
- History of exposure to the following cumulative doses of anthracyclines: Doxorubicin > 500 mg/m^2; Liposomal doxorubicin > 900 mg/m^2; Epirubicin > 720 mg/m^2
- History of clinically significant cardiac dysfunction
- Brain metastases that are untreated, or progressive, or have required any type of therapy (including radiation, surgery, or steroids) to control symptoms from brain metastases within 60 days prior to the first study treatment.
- History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, basal cell carcinoma, or synchronous or subsequent HER2-positive breast cancer or other malignancy with a similar expected curative outcome
Data sourced from ClinicalTrials.gov (NCT00951665). 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. Informational only — not medical advice.