Clinical trial NCT02490475: A Multiple-Dose Study of RhuMab 2C4 and Docetaxel in the Treatment of Advanced Solid Tumors
Official title: A Phase Ib, Open-Label, Multicenter Study of the Safety and Pharmacokinetics of the Combination of RhuMab 2C4 (Omnitarg), a Recombinant Humanized Antibody to HER2, and Docetaxel (Taxotere) in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumor
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2015-07-03
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).


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

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of Docetaxel in Combination of Pertuzumab
timeFrame: Cycle 1 Up to Day 15
Secondary outcomes:
measure: Plasma Decay Half Life (t1/2) for Pertuzumab in Combination With Docetaxel
timeFrame: Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22
measure: Maximum Observed Plasma Concentration (Cmax) for Pertuzumab in Combination With Docetaxel
timeFrame: Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22
measure: Area Under the Concentration Curve From Time Zero to the Last Visit (AUC [0-last]) for Pertuzumab in Combination With Docetaxel
timeFrame: Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22
measure: AUC From Time Zero to Infinity (AUC [0-infinity]) for Pertuzumab in Combination With Docetaxel
timeFrame: Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22
measure: Clearance (Cl) of Pertuzimab in Combination With Docetaxel
timeFrame: Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22
measure: Volume of Distribution (Vz) at Steady State of Pertuzumab in Combination With Docetaxel
timeFrame: Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22
measure: Mean Residence Time (MRT) of Pertuzumab
timeFrame: Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22
measure: Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria
timeFrame: Weeks 7 (Cycle 2),13 (Cycle 4) and Final Visit Up to 22 weeks
measure: Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint
timeFrame: Baseline, Weeks 7(Cycle 2), 13 (Cycle 4) and Final Visit Up to Week 22
measure: t1/2 for Docetaxel Alone and in Combination With Pertuzumab
timeFrame: Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose
measure: Tmax for Docetaxel Alone and in Combination With Pertuzumab
timeFrame: Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose
measure: Cmax for Docetaxel Alone and in Combination With Pertuzumab
timeFrame: Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose
measure: AUC(0-∞) for Docetaxel Alone and in Combination With Pertuzumab
timeFrame: Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose
measure: Vss for Docetaxel Alone and in Combination With Pertuzumab
timeFrame: Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose
measure: CL for Docetaxel Alone and in Combination With Pertuzumab
timeFrame: Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose
measure: Number of Participants With DLTs
timeFrame: From Baseline until 4 weeks after the end of treatment
Other outcomes:
Locations:
city: Rotterdam
country: Netherlands
city: Sutton
country: United Kingdom
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: