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

NCT02490475 | Completed Phase 1 Results

• 1 other identifier: BO17021
• 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 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).

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of Docetaxel in Combination of Pertuzumab

  A prior dose level was defined as an MTD if at a certain dose level, there were greater than or equal to (≥) 2 out of 6 participants who had Dose Limiting Toxicities (DLTs). If there were no DLTs or DLTs were seen in less than (\<) 2 participants in the highest dose level, that was considered as MTD. Participants received escalating doses of docetaxel and pertuzumab until DLTs were observed. DLTs were defined as any of the following: 1) Any non-hematological toxicity ≥ 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 greater than (\>) 7 days, 3) Febrile neutropenia, 4) Thrombocytopenia Grade 4 or any thrombocytopenia requiring platelet transfusion or 5) Any subjectively intolerable toxicity felt by the investigator to be related to either one of the compounds.

  Cycle 1 Up to Day 15

Secondary Outcomes (16)

• Plasma Decay Half Life (t1/2) for Pertuzumab in Combination With Docetaxel

  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

• Maximum Observed Plasma Concentration (Cmax) for Pertuzumab in Combination With Docetaxel

  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

• Area Under the Concentration Curve From Time Zero to the Last Visit (AUC [0-last]) for Pertuzumab in Combination With Docetaxel

  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

• AUC From Time Zero to Infinity (AUC [0-infinity]) for Pertuzumab in Combination With Docetaxel

  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

• Clearance (Cl) of Pertuzimab in Combination With Docetaxel

  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

Study Arms (3)

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

EXPERIMENTAL

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.

Drug: Docetaxel; Drug: RhuMab 2C4

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

EXPERIMENTAL

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.

Drug: Docetaxel; Drug: RhuMab 2C4

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

EXPERIMENTAL

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.

Drug: Docetaxel; Drug: RhuMab 2C4

Interventions

Docetaxel DRUG

Participants will receive docetaxel on Day 1 of each 3-week cycle as 60, 75, or 100 mg/m\^2 via IV infusion. Treatment may continue until disease progression, unacceptable toxicity, or consent withdrawal.

Also known as: Taxotere

RhuMab 2C4 + Docetaxel 100 mg/m^2 (Level 3); RhuMab 2C4 + Docetaxel 60 mg/m^2 (Level 1); RhuMab 2C4 + Docetaxel 75 mg/m^2 (Level 2)

RhuMab 2C4 DRUG

Participants will receive rhuMab 2C4 on Day 1 of each 3-week cycle as 420 mg via IV infusion. For Cycle 1 ony, rhuMab will be administered on Day 2, at least 24 hours after docetaxel and following an initial 840-mg loading dose. Treatment may continue until disease progression, unacceptable toxicity, or consent withdrawal.

Also known as: Omnitarg

RhuMab 2C4 + Docetaxel 100 mg/m^2 (Level 3); RhuMab 2C4 + Docetaxel 60 mg/m^2 (Level 1); RhuMab 2C4 + Docetaxel 75 mg/m^2 (Level 2)

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
• Signed informed consent, histologically or cytologicall confirmed advanced solid tumor, adequate cardiac function as documented by LVEF \>50% by ECHO or MUGA

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 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (2)

Unknown Facility

Rotterdam, 3075 EA, Netherlands

Location

Unknown Facility

Sutton, SM2 5PT, United Kingdom

Location

MeSH Terms

Interventions

Docetaxel; pertuzumab

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

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 2, 2015
• First Posted: July 3, 2015
• Study Start: February 1, 2004
• Primary Completion: April 1, 2006
• Study Completion: April 1, 2006
• Last Updated: May 17, 2017
• Results First Posted: November 25, 2015

Record last verified: 2017-04

Locations

NL (1); GB (1)