Clinical trial NCT00721266: A Dose-Escalation Study of RO5083945 in Patients With Metastatic and/or Locally Advanced Malignant Epidermal Growth Factor Receptor (EGFR)+ Solid Tumors.
Official title: An Open Label, Dose-escalation Study to Evaluate Safety, Pharmacokinetics and Tumor Growth Control Rate of RO5083945, a Glycoengineered Antibody Against EGFR, in Patients With Metastatic and/or Locally Advanced Malignant EGFR+ Solid Tumors.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2008-07-24
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will evaluate the pharmacokinetics, maximum tolerated dose and anti-tumor activity of RO5083945 in patients with metastatic and/or locally advanced malignant EGFR+ solid tumors. In the first part of the study, groups of patients will be sequentially enrolled to receive ascending doses of RO5083945 administered weekly, every 2 weeks or every 3 weeks. The starting dose of 50mg weekly will be escalated in subsequent groups of patients after a successful assessment of the safety, tolerability and pharmacokinetics of the previous dose. In Part 2 of the study, patients with EGFR+ and mutant KRAS colorectal cancer will be enrolled, and will receive RO5083945 at the recommended dose and regimen identified in Part 1. The anticipated time on study treatment is until disease progression, and the target sample size is \<100 individuals.


Eligibility criteria: Inclusion Criteria:

* adult patients, \>=18 years of age;
* centrally confirmed EGFR expression in tumor tissue;
* radiologically measurable or clinically evaluable disease;
* last dose of systemic anti-neoplastic therapy or radiotherapy \>=28 days prior to start of study;
* histologically or cytologically confirmed advanced stage, primary or metastatic EGFR+ solid tumors (Part 1);
* histologically or cytologically confirmed advanced stage, primary or metastatic EGFR+ and mutant KRAS colorectal cancer (Part 2);
* not more than 2 previous cytotoxic regimens for metastatic disease (Part 2).

Exclusion Criteria:

* history of grade 3-4 toxicity resulting from previous anti-EGFR treatment;
* known or suspected CNS metastases;
* wild type KRAS colorectal cancer (Part 2).

Primary outcomes:
measure: Pharmacokinetic parameters, and maximum tolerated dose (Part 1)
timeFrame: Throughout study
measure: Tumor growth control rate (CR, PR, SD) (Part 2)
timeFrame: Event driven
Secondary outcomes:
measure: AEs and laboratory parameters, pharmacodynamic parameters (Parts 1 and 2)
timeFrame: Throughout study
measure: Anti-tumor activity (ORR, DR, PFS) (Part 2)
timeFrame: Event driven
Other outcomes:
Locations:
city: Toulouse
country: France
city: Villejuif
country: France
city: Barcelona
country: Spain
city: Sevilla
country: Spain
city: Valencia
country: Spain
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Paz-Ares LG, Gomez-Roca C, Delord JP, Cervantes A, Markman B, Corral J, Soria JC, Berge Y, Roda D, Russell-Yarde F, Hollingsworth S, Baselga J, Umana P, Manenti L, Tabernero J. Phase I pharmacokinetic and pharmacodynamic dose-escalation study of RG7160 (GA201), the first glycoengineered monoclonal antibody against the epidermal growth factor receptor, in patients with advanced solid tumors. J Clin Oncol. 2011 Oct 1;29(28):3783-90. doi: 10.1200/JCO.2011.34.8888. Epub 2011 Sep 6.