A Study of RO5479599 Alone or in Combination With Cetuximab or Erlotinib in Participants With Metastatic and/or Locally Advanced Malignant Human Epidermal Growth Factor Receptor (HER3) Expressing Solid Tumors of Epithelial Cell Origin

Sponsor
Hoffmann-La Roche
Study ID
NCT01482377
Phase
PHASE1
Status
Completed

Conditions

  • Neoplasms

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • RO5479599 — DRUG
    RO5479599 will be administered Q2W or Q3W (other regimen could be explored based on observations during dose escalation part).
  • Cetuximab — DRUG
    Cetuximab will be administered via intravenous (IV) infusion at a starting dose of 400 mg/m\^2 for the first infusion, followed by doses of 250 mg/m\^2 for subsequent infusions.
  • Erlotinib — DRUG
    Erlotinib, at a dose of 150 mg will be administered.
  • zirconium-89-labeled RO5479599 — DRUG
    Single dose of radiolabeled drug will be administered.

Study Details

This dose-escalating study consists of 3 parts (A, B and C) and will evaluate the safety, pharmacokinetics and efficacy of RO5479599, alone or in combination with cetuximab or erlotinib, in participants with metastatic and/or locally advanced malignant HER3-positive solid tumors. Cohorts of participants will receive escalating doses of intravenous RO5479599 as monotherapy (Part A) or in combination with cetuximab (in Part B) or with erlotinib (in Part C) followed by an extension phase for each part. In an imaging substudy, participants will receive one or two doses of zirconium-89-labeled RO5479599 (89ZrRO5479599) in addition to unlabeled RO5479599 to evaluate the in vivo biodistribution and organ pharmacokinetics of RO5479599.

Key Dates

First listed
Nov 30, 2011
Start date
Dec 31, 2011
Status verified
Jan 2017
Primary completion
Feb 29, 2016
Completion
Feb 29, 2016

Study Design

Enrollment
145 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Part A: RO5479599 Dose Escalation
    Participants will receive a dose of 100 milligrams (mg) RO5479599 followed by dose escalation from Day 1 of Cycle 1. RO5479599 dose will be escalated as monotherapy in approximately 6 cohorts with dose increments between cohorts of up to 100 percent (%) until MTD.
  • Experimental: Part B: RO5479599 Dose Escalation + Cetuximab
    Participants will receive RO5479599 in combination with cetuximab. Escalation of RO5479599 in combination with cetuximab will start in a standard 3+3 design until MTD/OBD is reached. If the initial combination is not tolerated, further cohorts will be dosed with the same dose of cetuximab and lower doses of RO5479599.
  • Experimental: Part C: RO5479599 Dose Escalation + Erlotinib
    Participants will receive RO5479599 in combination with erlotinib. Escalation of RO5479599 in combination with erlotinib will start in a standard 3+3 design until MTD/OBD is reached. If the initial combination is not tolerated, further cohorts will be dosed with the same dose of erlotinib and lower doses of RO5479599.
  • Experimental: Imaging (IMG) Substudy
    RO5479599 will be administered with zirconium- 89-labeled RO5479599.

Primary Outcome Measure

Percentage of Participants With Adverse Events [ Time Frame: Baseline up to 28 days after last dose (approximately 48 months) ]

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