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

NCT02494596 | Completed Phase 1 Results

• 1 other identifier: BO17003
• Study Type: interventional
• Target: 19
• Locations: 2 countries
• Sites: 2

Brief Summary

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).

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of the Combination of Pertuzumab and Capecitabine

  MTD was defined as the highest tolerated dose combination of capecitabine (825 mg, 1000 mg or 1250 mg) and pertuzumab, without causing Dose Limiting Toxicities (DLTs). DLTs were defined as follows: 1) Any non-hematological toxicity greater than or equal to (≥) Grade 3 according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 except for fever, chills and flu-like symptoms, in spite of adequate toxicity management; 2) Grade 4 neutropenia lasting \> 7 days; 3) Febrile neutropenia; 4) Thrombocytopenia Grade 4 or any thrombocytopenia requiring platelet transfusion; 5) Any subjectively intolerable toxicity felt by the investigator to be related to either one of the compounds. Participants who withdrew from the study without completing the first treatment cycle for reasons other than DLT were not considered evaluable for DLT. MTD was measured in mg/m\^2.

  Cycle 1 (3 Weeks)

Secondary Outcomes (11)

• Percentage of Participants With DLTs

  Cycle 1 (3 Weeks)

• Plasma Half-Life (t1/2) of Pertuzumab

  Cycle 1: Days 2, 5, 8 and 15 Postdose; Cycle 2: Day 1 at drug administration, predose and 15 minutes postdose, and Predose on Days 8, 15 and 22

• Maximum Plasma Concentration (Cmax) of Pertuzumab

  Cycle 1: Days 2, 5, 8 and 15 Postdose; Cycle 2: Day 1 at drug administration, predose and 15 minutes postdose, and predose on Days 8, 15 and 22

• Time to Maximum Plasma Concentration (Tmax) of Pertuzumab

  Cycle 1: Days 2, 5, 8 and 15 Postdose; Cycle 2: Day 1 at drug administration, predose and 15 minutes postdose, and predose on Days 8, 15 and 22

• Area Under the Concentration Curve From Time Zero to Last Measurement (AUC 0-last) of Pertuzumab

  Cycle 1: Days 2, 5, 8 and 15 Postdose; Cycle 2: Day 1 at drug administration, predose and 15 minutes postdose, and predose on Days 8, 15 and 22

Study Arms (3)

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

EXPERIMENTAL

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.

Drug: Capecitabine; Drug: RhuMab 2C4

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

EXPERIMENTAL

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.

Drug: Capecitabine; Drug: RhuMab 2C4

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

EXPERIMENTAL

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.

Drug: Capecitabine; Drug: RhuMab 2C4

Interventions

Capecitabine DRUG

Participants will receive capecitabine on Days 1 to 14 of each 3-week cycle as 825, 1000, or 1250 mg/m\^2 PO twice daily. Treatment may continue until disease progression, unacceptable toxicity, or consent withdrawal.

Also known as: Xeloda

RhuMab 2C4 + Capecitabine 1000 mg/m^2 (Level 2); RhuMab 2C4 + Capecitabine 1250 mg/m^2 (Level 3); RhuMab 2C4 + Capecitabine 825 mg/m^2 (Level 1)

RhuMab 2C4 DRUG

Participants will receive rhuMab 2C4 on Day 1 of each 3-week cycle as 1050 mg via IV infusion. Treatment may continue until disease progression, unacceptable toxicity, or consent withdrawal.

Also known as: Omnitarg

RhuMab 2C4 + Capecitabine 1000 mg/m^2 (Level 2); RhuMab 2C4 + Capecitabine 1250 mg/m^2 (Level 3); RhuMab 2C4 + Capecitabine 825 mg/m^2 (Level 1)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (2)

Unknown Facility

Barcelona, 08036, Spain

Location

Unknown Facility

Manchester, M20 4BX, United Kingdom

Location

MeSH Terms

Interventions

Capecitabine; pertuzumab

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2015
• First Posted: July 10, 2015
• Study Start: January 1, 2004
• Primary Completion: September 1, 2005
• Study Completion: September 1, 2005
• Last Updated: November 10, 2015
• Results First Posted: September 30, 2015

Record last verified: 2015-10

Locations

GB (1); ES (1)