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A Study of RO5479599 Alone or in Combination With Cetuximab or Erlotinib in Patients With Metastatic and/or Locally Advanced Malignant HER3-Positive Solid Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2014 by Hoffmann-La Roche
Information provided by (Responsible Party):
Hoffmann-La Roche Identifier:
First received: November 28, 2011
Last updated: November 24, 2014
Last verified: November 2014

This multicenter, open-label, 3-Part dose-escalating study will evaluate the saf ety, pharmacokinetics and efficacy of RO5479599, alone or in combination with ce tuximab or Erlotinib, in patients with metastatic and/or locally advanced malign ant HER3-positive solid tumors. Cohorts of patients will receive escalating dose s of intravenous RO5479599 as monotherapy (Part A) or in combination with cetuxi mab (Part B) or erlotinib (Part C). Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs. In an imaging substudy, p atients will receive one or two doses of zirconium-89-labeled RO5479599 in addit ion to unlabeled RO5479599 to evaluate the in vivo biodistribution and organ pha rmacokinetics of RO5479599.

Condition Intervention Phase
Drug: RO5479599
Drug: cetuximab
Drug: erlotinib
Drug: zirconium-89-labeled RO5479599
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase Ia/Ib, Open-label, Multicenter, Dose-escalation Study Followed by an Extension Phase to Evaluate Safety, Pharmacokinetics and Activity of RO5479599, a Glycoengineered Antibody Against HER3, Administered Either Alone (Part A) or in Combination With Cetuximab (Part B) or in Combination With Erlotininb (Part C) in Patients With Metastatic and/or Locally Advanced Malignant HER3-positive Solid Tumors of Ephitelian Cell Origin

Resource links provided by NLM:

Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Safety (Part A, including maximum tolerated dose): Incidence of adverse events [ Time Frame: 72 weeks ] [ Designated as safety issue: No ]
  • Safety (Part B and C): Incidence of adverse events [ Time Frame: 50 weeks ] [ Designated as safety issue: No ]
  • Pharmacokinetics (Parts A, B and C): Area under the concentration - time curve [ Time Frame: 200 weeks ] [ Designated as safety issue: No ]
  • IMG Substudy: In vivo biodistribution as determined by positron emission tomography (PET) scan [ Time Frame: up to Day 8 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Part A: Recommended phase II dose (RPTD) in monotherapy [ Time Frame: 72 weeks ] [ Designated as safety issue: No ]
  • Part B: Recommended phase II dose in combination with cetuximab [ Time Frame: 36 weeks ] [ Designated as safety issue: No ]
  • Part C: Recommended phase II dose in combination with erlotinib [ Time Frame: 36 weeks ] [ Designated as safety issue: No ]
  • Objective response rate (ORR), tumor assessments according to RECIST criteria [ Time Frame: 200 weeks ] [ Designated as safety issue: No ]
  • Disease control rate (SD) [ Time Frame: 200 weeks ] [ Designated as safety issue: No ]
  • Duration of response [ Time Frame: 200 weeks ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: 200 weeks ] [ Designated as safety issue: No ]
  • IMG Substudy: Target saturation by RO5479599, defined as decrease in tissue uptake of radioactivity concentration [ Time Frame: up to Day 8 ] [ Designated as safety issue: No ]

Estimated Enrollment: 160
Study Start Date: December 2011
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A Drug: RO5479599
Cohorts receiving multiple escalating doses intravenously
Experimental: B Drug: RO5479599
Cohorts receiving multiple escalating doses intravenously
Drug: cetuximab
standard doses
Experimental: C Drug: RO5479599
Cohorts receiving multiple escalating doses intravenously
Drug: erlotinib
standard doses
Experimental: IMG Substudy Drug: RO5479599
Cohorts receiving multiple escalating doses intravenously
Drug: zirconium-89-labeled RO5479599
single dose


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Adult patients, >/= 18 years of age
  • European Cooperative Oncology Group (ECOG) performance status 0-2
  • Histologically confirmed metastatic and/or locally advanced malignant HER3-expressing solid tumors of epithelian origin
  • Availability of tissue and willingness to perform fresh pretreatment biopsies
  • Patients for whom no standard therapy exists
  • All acute toxic effects of any prior radiotherapy, chemotherapy or surgical procedure must have resolved to Grade </= 1, except for alopecia and Grade 2 peripheral neuropathy
  • Adequate hematological, renal and liver function
  • Patient's with Gilbert's syndrome will be eligible for the study
  • Part B extension cohort: In addition to the above inclusion criteria, patients will be eligible if they have metastatic and/or locally advanced non-small cell lung cancer or squamous cell carcinoma of the head and neck or colorectal cancer (wild type with positive EGFR expression)
  • Part C extension cohort: In addition to the above inclusion criteria, patients will be eligible only if they have metastatic and/or locally advanced squamous non-small cell lung cancer

Exclusion Criteria:

  • Known or clinically suspected CNS primary tumors or metastases including leptomeningeal metastases, except for previously treated CNS metastases that are asymptomatic and did not require steroids or enzyme-inducing anticonvulsants in the last 14 days
  • Evidence of significant uncontrolled concomitant diseases or disorders
  • Active or uncontrolled infections
  • Known HIV infection
  • Therapy with antibody or immunotherapy concurrently or within 14 days prior to first dose of study drug
  • Regular immunosuppressive therapy
  • Concurrent high dose of systemic corticosteroids (> 20 mg/day dexamethasone or equivalent for > 7 consecutive days)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01482377

Contact: Reference Study ID Number: BP27771 888-662-6728 (U.S. Only)

Active, not recruiting
København, Denmark, 2100
Amsterdam, Netherlands, 1066 CX
Groningen, Netherlands, 9713 GZ
Rotterdam, Netherlands, 3075EA
Utrecht, Netherlands, 3584 CW
Barcelona, Spain, 08003
Barcelona, Spain, 08035
Sevilla, Spain, 41013
Active, not recruiting
Valencia, Spain, 46010
Sponsors and Collaborators
Hoffmann-La Roche
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided

Responsible Party: Hoffmann-La Roche Identifier: NCT01482377     History of Changes
Other Study ID Numbers: BP27771, 2011-002698-53
Study First Received: November 28, 2011
Last Updated: November 24, 2014
Health Authority: The Netherlands: Central Committee on Research involving Human Subjects

Additional relevant MeSH terms:
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses processed this record on November 24, 2014