Phase 2
Completed N=42
A Study of Trastuzumab Emtansine (T-DM1) in Combination With Docetaxel, and Potentially Pertuzumab, in Participants With Advanced Breast Cancer
Source: ClinicalTrials.gov NCT00934856 ↗Enrolled (actual)
42
Serious AEs
28.6%
Results posted
Apr 2017
Primary outcomePrimary: Number of Participants With Dose Limiting Toxicity (DLT) - MBC and LABC Feasibility Population — 2; 1; 0; 1 participants
Summary
This is an open-label, multi-center, non-randomized study of the safety and tolerability of the combination of T-DM1 plus docetaxel for the treatment of participants with metastatic breast cancer (MBC) and of T-DM1 plus docetaxel with or without pertuzumab, for the treatment of participants with locally advanced breast cancer (LABC). The study comprises an initial dose finding (feasibility) part to determine the maximum tolerated dose (MTD) of T-DM1 and docetaxel, followed by an extension part aiming to consolidate the safety and efficacy of the recommended docetaxel/T-DM1 combination regimen.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Dose Limiting Toxicity (DLT) - MBC and LABC Feasibility Population |
2; 1; 0; 1; 2; 2 | — |
| PRIMARY Percentage of Participants With Adverse Events (AEs) or Serious AEs (SAEs) - MBC and LABC Population |
100; 100; 100; 100; 100; 100 | — |
| SECONDARY Percentage of Participants With Progression-Free Survival (PFS) Event - MBC Population |
60.0 | — |
| SECONDARY PFS - MBC Population |
13.8 | — |
| SECONDARY Percentage of Participants With a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) - MBC Population |
80.0 | — |
| SECONDARY Percentage of Participants With Treatment Failure - MBC Population |
64.0 | — |
| SECONDARY Time to Treatment Failure (TTF) - MBC Population |
13.8 | — |
| SECONDARY Percentage of Participants With CR or PR or Stable Disease (SD) for at Least 6 Months [Clinical Benefit Rate (CBR)] - MBC Population |
92.0 | — |
| SECONDARY Duration of Response - MBC Population |
12.4 | — |
| SECONDARY Percentage of Participants With Pathological CR (pCR) - LABC Population |
60.0; 60.6 | — |
| SECONDARY Percentage of Participants With a BOR of CR or PR - LABC Population |
70.0; 51.5 | — |
| SECONDARY Number of Participants With Anti-Therapeutic Antibody (ATA) Response to Trastuzumab - MBC and LABC Population |
3; 3 | — |
| SECONDARY Maximum Observed Concentration (Cmax) of Serum Trastuzumab Emtansine |
78.6; 76.2; 85.7; 78.7; 93.7; 80.2 | — |
| SECONDARY Apparent Terminal Half-Life (t1/2) of Serum Trastuzumab Emtansine |
2.79; 3.45; 3.46; 3.14; 3.85; 3.62 | — |
| SECONDARY Area Under the Concentration-Time Curve From Time 0 to Infinity (AUCinf) of Serum Trastuzumab Emtansine |
396; 447; 442; 471; 556; 488 | — |
| SECONDARY Clearance (CL) of Serum Trastuzumab Emtansine |
8.94; 8.87; 8.48; 5.21; 7.16; 7.68 | — |
| SECONDARY Volume of Distribution at Steady State (Vss) of Serum Trastuzumab Emtansine |
22.1; 33.2; 33.2; 17.7; 31.4; 28.8 | — |
| SECONDARY Cmax of Total Serum Trastuzumab |
88.7; 89.2; 120; 85.8; 97.7; 113 | — |
| SECONDARY t1/2 of Total Serum Trastuzumab |
6.44; 6.38; 8.12; 6.67; 7.83; 9.91 | — |
| SECONDARY AUCinf of Total Serum Trastuzumab |
785; 707; 1210; 809; 1040; 1570 | — |
| SECONDARY CL of Total Serum Trastuzumab |
6.78; 5.45; 4.22; 3.32; 3.71; 3.38 | — |
| SECONDARY Vss of Total Serum Trastuzumab |
27; 41.3; 36.5; 24.6; 36.4; 35.2 | — |
| SECONDARY Cmax of Plasma N2'-Deacetyl-N2'-(3-mercapto-1-oxopropyl)-Maytansine (DM1) |
3.55; 3.42; 4.51; 3.34; 3.9; 4.65 | — |
| SECONDARY t1/2 of Plasma DM1 |
1.12; 1.2; 1.87; 3.75; 2.91; 3.32 | — |
| SECONDARY AUCinf of Plasma DM1 |
5.72; 5.01; 9.38; 17.8; 20; 18.5 | — |
| SECONDARY Cmax of Plasma Docetaxel |
500; 1300; 1470; 1710; 2950; 791 | — |
| SECONDARY t1/2 of Plasma Docetaxel |
6.83; 5.17; 4.25; 8.29; 8.76; 7.7 | — |
| SECONDARY AUCinf of Plasma Docetaxel |
1050; 1560; 1540; 2140; 4020; 1700 | — |
| SECONDARY CL of Plasma Docetaxel |
82.2; 58.3; 42.8; 39.5; 30.5; 59 | — |
| SECONDARY Vss of Plasma Docetaxel |
530; 203; 75; 126; 116; 380 | — |
Eligibility Criteria
Inclusion Criteria
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (ECOG performance status of 2 will be allowed if only due to debilitating bone disease)
- HER2-positive metastatic or locally advanced breast cancer
For MBC participants:
- Documented metastatic or inoperable locally advanced (without meeting LABC criteria) disease, amenable for treatment with docetaxel
- History of disease progression within 3 months prior to study entry
For LABC participants:
- Newly diagnosed locally advanced breast cancer, Stage IIA-IIIC (American Joint Committee on Cancer [AJCC] staging system)
Exclusion Criteria
- Significant cardiac disease
- Inadequate bone marrow, liver or renal function
For MBC participants:
- Participants must not have received radiotherapy for the treatment of metastatic or locally recurrent/advanced disease other than for the relief of pain in progressing metastatic bone lesions and/or brain metastases
- Brain metastases that are untreated, symptomatic or require therapy to control symptoms; or any radiation, surgery, or other therapy to control symptoms from brain metastasis within 2 months of the first study treatment.
For LABC participants:
- Clinically or radiologically detectable metastasis (M1 disease)
- Participants for whom surgery as primary intent procedure is the best option to treat their disease
- Participants must not have received any systemic or loco-regional anti-cancer therapy for the treatment of locally advanced disease
Data sourced from ClinicalTrials.gov (NCT00934856). 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.