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 October 2014 by Hoffmann-La Roche
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01482377
First received: November 28, 2011
Last updated: October 20, 2014
Last verified: October 2014

November 28, 2011
October 20, 2014
December 2011
August 2015   (final data collection date for primary outcome measure)
  • 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 ]
Same as current
Complete list of historical versions of study NCT01482377 on ClinicalTrials.gov Archive Site
  • 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 ]
  • 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 ]
Not Provided
Not Provided
 
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
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

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.

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Neoplasms
  • Drug: RO5479599
    Cohorts receiving multiple escalating doses intravenously
  • Drug: cetuximab
    standard doses
  • Drug: erlotinib
    standard doses
  • Drug: zirconium-89-labeled RO5479599
    single dose
  • Experimental: A
    Intervention: Drug: RO5479599
  • Experimental: B
    Interventions:
    • Drug: RO5479599
    • Drug: cetuximab
  • Experimental: C
    Interventions:
    • Drug: RO5479599
    • Drug: erlotinib
  • Experimental: IMG Substudy
    Interventions:
    • Drug: RO5479599
    • Drug: zirconium-89-labeled RO5479599
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
160
August 2015
August 2015   (final data collection date for primary outcome measure)

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)
Both
18 Years and older
No
Contact: Reference Study ID Number: BP27771 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. Only) global.rochegenentechtrials@roche.com
Spain,   Netherlands,   Denmark
 
NCT01482377
BP27771, 2011-002698-53
Not Provided
Hoffmann-La Roche
Hoffmann-La Roche
Not Provided
Study Director: Clinical Trials Hoffmann-La Roche
Hoffmann-La Roche
October 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP