NCT01482377

Brief Summary

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
145

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Dec 2011

Longer than P75 for phase_1

Geographic Reach
4 countries

12 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 28, 2011

Completed
2 days until next milestone

First Posted

Study publicly available on registry

November 30, 2011

Completed
1 day until next milestone

Study Start

First participant enrolled

December 1, 2011

Completed
4.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2016

Completed
Last Updated

January 27, 2017

Status Verified

January 1, 2017

Enrollment Period

4.2 years

First QC Date

November 28, 2011

Last Update Submit

January 26, 2017

Conditions

Neoplasms

Outcome Measures

Primary Outcomes (4)

  • Percentage of Participants With Adverse Events

    Baseline up to 28 days after last dose (approximately 48 months)

  • Maximum Tolerated Dose (MTD) or Optimal Biological Dose (OBD) of RO5479599

    Cycle 1 Day 1 (cycle length = 14 or 21 days) up to 28 days

  • Number of Participants With Dose Limiting Toxicities (DLTs)

    Cycle 1 Day 1 (cycle length = 14 or 21 days) up to 28 days

  • Standardized Uptake Value (SUV) of 89ZrRO5479599 Determined by Positron Emission Tomography (PET) Scan Over Regions of Interest (ROI)

    From baseline to Day 8

Secondary Outcomes (48)

  • Percentage Change From Baseline in Standardized Uptake Value (SUV) of 89ZrRO5479599 at Pharmacodynamic (PD) active dose as Determined by PET Scan

    From baseline to Day 22

  • Part A: Recommended Phase II Dose (RPTD) of RO5479599 in Monotherapy

    Cycle 1 Day 1 (cycle length = 14 or 21 days) up to 28 days

  • Part B: Recommended Phase II Dose of RO5479599 in Combination With Cetuximab

    Cycle 1 Day 1 (cycle length = 14 or 21 days) up to 28 days

  • Part C: Recommended Phase II Dose of RO5479599 in Combination With Erlotinib

    Cycle 1 Day 1 (cycle length = 14 or 21 days) up to 28 days

  • Percentage of Participants With Objective Response According to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

    From screening to disease progression, death, withdrawal, or end of study (assessed at screening, then every eighth week for two weekly schedule [Q2W] and every ninth week for three weekly schedule [Q3W] up to approximately 48 months)

  • +43 more secondary outcomes

Study Arms (4)

Part A: RO5479599 Dose Escalation

EXPERIMENTAL

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.

Drug: RO5479599

Part B: RO5479599 Dose Escalation + Cetuximab

EXPERIMENTAL

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.

Drug: RO5479599Drug: Cetuximab

Part C: RO5479599 Dose Escalation + Erlotinib

EXPERIMENTAL

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.

Drug: RO5479599Drug: Erlotinib

Imaging (IMG) Substudy

EXPERIMENTAL

RO5479599 will be administered with zirconium- 89-labeled RO5479599.

Drug: RO5479599Drug: zirconium-89-labeled RO5479599

Interventions

RO5479599DRUG

RO5479599 will be administered Q2W or Q3W (other regimen could be explored based on observations during dose escalation part).

Imaging (IMG) SubstudyPart A: RO5479599 Dose EscalationPart B: RO5479599 Dose Escalation + CetuximabPart C: RO5479599 Dose Escalation + Erlotinib
CetuximabDRUG

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.

Part B: RO5479599 Dose Escalation + Cetuximab
ErlotinibDRUG

Erlotinib, at a dose of 150 mg will be administered.

Part C: RO5479599 Dose Escalation + Erlotinib
zirconium-89-labeled RO5479599DRUG

Single dose of radiolabeled drug will be administered.

Imaging (IMG) Substudy

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • All Parts (A, B and C)
  • European Cooperative Oncology Group (ECOG) performance status 0-2
  • Histologically confirmed metastatic and/or locally advanced malignant HER3-expressing solid tumors of epithelial origin
  • Availability of tissue and willingness to perform fresh pretreatment biopsies
  • Participants for whom no standard therapy exists
  • All acute toxic effects of any prior radiotherapy, chemotherapy or surgical procedure must have resolved to Grade less than or equal to (\</= 1), except for alopecia and Grade 2 peripheral neuropathy
  • Adequate hematological, renal and liver function
  • Participants with Gilbert's syndrome will be eligible for the study

You may not qualify if:

  • Known or clinically suspected central nervous system (CNS) primary tumors or metastases including leptomeningeal metastases. History or clinical evidence of CNS metastases unless they have been previously treated, are asymptomatic and have had no requirement for steroids or enzyme-inducing anticonvulsants in the last 14 days
  • Evidence of significant uncontrolled concomitant diseases or disorders
  • Active or uncontrolled infections
  • Known Human immuno deficiency virus (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 (greater than (\>) 20 milligrams per day \[mg/day\] dexamethasone or equivalent for \> 7 consecutive days)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (12)

Rigshospitalet, Onkologisk Klinik

København Ø, 2100, Denmark

Location

Antoni van Leeuwenhoek Ziekenhuis

Amsterdam, 1066 CX, Netherlands

Location

Academ Ziekenhuis Groningen; Medical Oncology

Groningen, 9713 GZ, Netherlands

Location

Erasmus Medisch Centrum Rotterdam; Lokatie Daniel den Hoed

Rotterdam, 3075EA, Netherlands

Location

Utrecht University Medical Centre; Dept of Medical Oncology and UPC

Utrecht, 3584 CW, Netherlands

Location

National Cancer Center

Gyeonggi-do, 10408, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Hospital del Mar; Servicio de Oncologia

Barcelona, Barcelona, 08003, Spain

Location

Hospital Univ Vall d'Hebron; Servicio de Oncologia

Barcelona, Barcelona, 08035, Spain

Location

Centro Integral Oncologico Clara Campal (CIOCC); Dirección Médica

Madrid, Madrid, 28050, Spain

Location

Hospital Universitario Virgen del Rocio; Servicio de Oncologia

Seville, Sevilla, 41013, Spain

Location

Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia

Valencia, Valencia, 46010, Spain

Location

Related Publications (1)

  • Kim HS, Han JY, Shin DH, Lim KY, Lee GK, Kim JY, Jacob W, Ceppi M, Weisser M, James I. EGFR and HER3 signaling blockade in invasive mucinous lung adenocarcinoma harboring an NRG1 fusion. Lung Cancer. 2018 Oct;124:71-75. doi: 10.1016/j.lungcan.2018.07.026. Epub 2018 Jul 20.

    PMID: 30268483DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

lumretuzumabCetuximabErlotinib Hydrochloride

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsQuinazolinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Study Officials

  • Clinical Trials

    Hoffmann-La Roche

    STUDY DIRECTOR

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

November 28, 2011

First Posted

November 30, 2011

Study Start

December 1, 2011

Primary Completion

February 1, 2016

Study Completion

February 1, 2016

Last Updated

January 27, 2017

Record last verified: 2017-01

Locations

ES(5)NL(4)DK(1)KR(2)