Phase 1
Completed N=19
A Multiple-Dose Study of RhuMab 2C4 and Docetaxel in the Treatment of Advanced Solid Tumors
Source: ClinicalTrials.gov NCT02490475 ↗Enrolled (actual)
19
Serious AEs
42.1%
Results posted
Nov 2015
Primary outcomePrimary: Maximum Tolerated Dose (MTD) of Docetaxel in Combination of Pertuzumab — 75.0 mg/m^2
Summary
This study will evaluate the safety, tolerability, and pharmacokinetics of the combination of rhuMab 2C4 (Perjeta) and docetaxel (Taxotere) in participants with advanced solid tumors that have progressed during or after standard therapy, or for which no standard therapy is available. Participants will be enrolled and evaluated for dose-limiting toxicities (DLTs) in escalating-dose cohorts in order to determine the maximum tolerated dose (MTD).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Tolerated Dose (MTD) of Docetaxel in Combination of Pertuzumab |
75.0 | — |
| SECONDARY Plasma Decay Half Life (t1/2) for Pertuzumab in Combination With Docetaxel |
12.65; 11.65; NA; 19.02; NA; 18.46 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) for Pertuzumab in Combination With Docetaxel |
301.0; 255.0; NA; 368.0; NA; 150.0 | — |
| SECONDARY Area Under the Concentration Curve From Time Zero to the Last Visit (AUC [0-last]) for Pertuzumab in Combination With Docetaxel |
2390; 1749; NA; 3500; NA; 1491 | — |
| SECONDARY AUC From Time Zero to Infinity (AUC [0-infinity]) for Pertuzumab in Combination With Docetaxel |
3951; 2796; NA; 6856; NA; 2762 | — |
| SECONDARY Clearance (Cl) of Pertuzimab in Combination With Docetaxel |
282; 329; NA; 167; NA; 169 | — |
| SECONDARY Volume of Distribution (Vz) at Steady State of Pertuzumab in Combination With Docetaxel |
5214; 5355; NA; 4672; NA; 4233 | — |
| SECONDARY Mean Residence Time (MRT) of Pertuzumab |
17.8; 15.8; NA; 29.5; NA; 25.8 | — |
| SECONDARY Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria |
0.0; 0.0; 0.0; 0.0; 0.0; 0.0 | — |
| SECONDARY Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint |
83.3; 100.0; 100.0; 100.0; 0.0; 0.0 | — |
| SECONDARY t1/2 for Docetaxel Alone and in Combination With Pertuzumab |
17.7; NA; 12.0; NA; 8.92; NA | — |
| SECONDARY Tmax for Docetaxel Alone and in Combination With Pertuzumab |
0.50; NA; 0.50; NA; 0.90; NA | — |
| SECONDARY Cmax for Docetaxel Alone and in Combination With Pertuzumab |
1642; NA; 3128; NA; 5450; NA | — |
| SECONDARY AUC(0-∞) for Docetaxel Alone and in Combination With Pertuzumab |
1838; NA; 3744; NA; 5930; NA | — |
| SECONDARY Vss for Docetaxel Alone and in Combination With Pertuzumab |
786981; NA; 410174; NA; 254233; NA | — |
| SECONDARY CL for Docetaxel Alone and in Combination With Pertuzumab |
33128; NA; 22013; NA; 18913; NA | — |
| SECONDARY Number of Participants With DLTs |
0; 2; 0; 2 | — |
Eligibility Criteria
Inclusion Criteria
- Adults at least 18 years of age
- Easter Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Life expectancy at least 12 weeks
- Locally advanced or metastatic solid tumor with at least 1 measurable lesion, which has progressed during/after standard therapy
- Human epidermal growth factor receptor 2 (HER2)-negative among participants with breast cancer
- Negative pregnancy test or use of an adequate contraceptive method among women of childbearing potential
- Adequate hematologic, hepatic, and renal function
- Signed informed consent, histologically or cytologicall confirmed advanced solid tumor, adequate cardiac function as documented by LVEF >50% by ECHO or MUGA
Exclusion Criteria
- Clinical evidence of central nervous system (CNS) metastases
- Prior chemotherapy, radiotherapy, or immunotherapy within 4 weeks, or hormone therapy within 2 weeks of study Day 1
- History of neuropathy Grade 2 or worse, or any unresolved residual chemotherapy effects
- Prior HER2-active agents or docetaxel
- Any investigational agent within 28 days of study drug
- Prior cumulative doxorubicin dose greater than (>) 360 mg/m^2 or equivalent
- Significant cardiovascular disease
- Active/uncontrolled concurrent illness or infection-
- Major surgery or trauma within 4 weeks of study Day 1
Data sourced from ClinicalTrials.gov (NCT02490475). 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.