A Dose-Escalation Study of RO5083945 in Patients With Metastatic and/or Locally Advanced Malignant Epidermal Growth Factor Receptor (EGFR)+ Solid Tumors.

Study Overview
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Brief Summary
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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.

Official Title
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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.

Conditions
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Neoplasms

Intervention / Treatment
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* Drug: RO5083945


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: RO5083945<br>* Administered iv, either weekly, every 2 weeks or every 3 weeks, at escalating doses (with a starting dose of 50mg weekly (Part 1)). Recommended dose administered iv, either weekly, every 2 weeks or every 3 weeks (Part 2).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameters, and maximum tolerated dose (Part 1) |  | Throughout study | 
| Tumor growth control rate (CR, PR, SD) (Part 2) |  | Event driven | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AEs and laboratory parameters, pharmacodynamic parameters (Parts 1 and 2) |  | Throughout study | 
| Anti-tumor activity (ORR, DR, PFS) (Part 2) |  | Event driven |