A Phase Ib, Open-label, Multicenter Study of the Safety and PK of the Combination of rhuMAb2c4 (Omnitarg), a Recombinant Humanized Antibody to HER2, and Capecitabine (Xeloda) in Patients With Advanced Solid Tumors

Roche

Status and phase: Completed; Phase 1

Conditions: Solid Tumor

Treatments: Drug: RhuMab 2C4; Drug: Capecitabine

Study type: Interventional

Funder types: Industry

Identifiers

NCT02494596

BO17003

Details and patient eligibility

About

This study will evaluate the safety, tolerability, and pharmacokinetics of the combination of rhuMab 2C4(Perjeta) and capecitabine (Xeloda) 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

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 palmar plantar syndrome Grade 2 or worse, or any unresolved residual chemotherapy effects
• Prior HER2-active agents, continuous intravenous (IV) 5-fluorouracil, capecitabine, or other fluoropyrimidine
• Any investigational agent within 28 days of study start
• 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)

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19 participants in 3 patient groups

RhuMab 2C4 + Capecitabine 1000 mg/m^2 (Level 2)

Experimental group

Description:

Participants will receive a single 1000-mg/m\^2 dose of oral (PO) capecitabine on Day -7 for pretreatment assessment. Capecitabine will then be administered on Days 1 to 14 of each 3-week cycle at a dose of 1000 mg/m\^2 twice daily, and rhuMab 2C4 will be given on Day 1 of each 3-week cycle as a fixed-dose 1050-mg IV infusion. The incidence of DLTs will be used to guide intrapatient dose modification, as well as subsequent enrollment.

Treatment:

Drug: Capecitabine

Drug: RhuMab 2C4

RhuMab 2C4 + Capecitabine 1250 mg/m^2 (Level 3)

Experimental group

Description:

Participants will receive a single 1250-mg/m\^2 dose of PO capecitabine on Day -7 for pretreatment assessment. Capecitabine will then be administered on Days 1 to 14 of each 3-week cycle at a dose of 1250 mg/m\^2 twice daily, and rhuMab 2C4 will be given on Day 1 of each 3-week cycle as a fixed-dose 1050-mg IV infusion. The incidence of DLTs will be used to guide intrapatient dose modification, as well as subsequent enrollment.

Treatment:

Drug: Capecitabine

Drug: RhuMab 2C4

RhuMab 2C4 + Capecitabine 825 mg/m^2 (Level 1)

Experimental group

Description:

Participants will receive a single 825-mg/m\^2 dose of PO capecitabine on Day -7 for pretreatment assessment. Capecitabine will then be administered on Days 1 to 14 of each 3-week cycle at a dose of 825 mg/m\^2 twice daily, and rhuMab 2C4 will be given on Day 1 of each 3-week cycle as a fixed-dose 1050-mg IV infusion. The incidence of DLTs will be used to guide intrapatient dose modification, as well as subsequent enrollment.

Treatment:

Drug: Capecitabine

Drug: RhuMab 2C4