A Multiple-Dose Study of RhuMab 2C4 and Docetaxel in the Treatment of Advanced Solid Tumors

Roche

Status and phase: Completed; Phase 1

Conditions: Solid Tumor

Treatments: Drug: RhuMab 2C4; Drug: Docetaxel

Study type: Interventional

Funder types: Industry

Identifiers

NCT02490475

BO17021

Details and patient eligibility

About

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).

Enrollment: 19 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

19 participants in 3 patient groups

RhuMab 2C4 + Docetaxel 100 mg/m^2 (Level 3)

Experimental group

Description:

Docetaxel will be administered via intravenous (IV) infusion on Day 1 of each 3-week cycle at a dose of 100 mg/m\^2 per day, and rhuMab 2C4 will be given on Day 1 of each 3-week cycle as a fixed-dose 420-mg IV infusion. For Cycle 1 only, rhuMab 2C4 administration will be delayed to Day 2 with an initial 840-mg loading dose. The incidence of DLTs will be used to guide intrapatient dose modification, as well as subsequent enrollment.

Treatment:

Drug: Docetaxel

Drug: RhuMab 2C4

RhuMab 2C4 + Docetaxel 60 mg/m^2 (Level 1)

Experimental group

Description:

Docetaxel will be administered via IV infusion on Day 1 of each 3-week cycle at a dose of 60 mg/m\^2 per day, and rhuMab 2C4 will be given on Day 1 of each 3-week cycle as a fixed-dose 420-mg IV infusion. For Cycle 1 only, rhuMab 2C4 administration will be delayed to Day 2 with an initial 840-mg loading dose. The incidence of DLTs will be used to guide intrapatient dose modification, as well as subsequent enrollment.

Treatment:

Drug: Docetaxel

Drug: RhuMab 2C4

RhuMab 2C4 + Docetaxel 75 mg/m^2 (Level 2)

Experimental group

Description:

Docetaxel will be administered via IV infusion on Day 1 of each 3-week cycle at a dose of 75 mg/m\^2 per day, and rhuMab 2C4 will be given on Day 1 of each 3-week cycle as a fixed-dose 420-mg IV infusion. For Cycle 1 only, rhuMab 2C4 administration will be delayed to Day 2 with an initial 840-mg loading dose. The incidence of DLTs will be used to guide intrapatient dose modification, as well as subsequent enrollment.

Treatment:

Drug: Docetaxel

Drug: RhuMab 2C4