A Study of RO5429083 in Patients With Metastatic and/or Locally Advanced, CD44-Expressing, Malignant Solid Tumors

Study Overview
=================
Brief Summary
-----------------
This open-label 2-arm study will assess the pharmacokinetics, pharmacodynamics, safety and efficacy of RO5429083 in patients with metastatic and/or locally advanced CD44-expressing malignant solid tumors. In Part A, cohorts of patients will receive RO5429083 intravenously at escalating doses. In Part B, patients will receive 89Zr-labelled RO5429083 in Cycles 1 and/or 2, followed by RO5429083. For all patients there will be an option to continue treatment with RO5429083 until disease progression or unacceptable toxicity occurs.

Official Title
-----------------
Open-Label Multicenter 2-Arm Phase I Study of RO5429083 With Dose-Escalation and Extension Cohorts, and Imaging Cohorts With RO5429083 and 89Zr-labeled RO5429083, in Patients With Metastatic and/or Locally Advanced, CD44-Expressing, Malignant Solid Tumors

Conditions
-----------------
Neoplasms

Intervention / Treatment
-----------------
* Drug: RO5429083
* Drug: RO5429083


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult patients, >/= 18 years of age Metastatic and/or locally advanced malignant CD44-expressing solid tumors Patients with disease progression on standard therapy, or have tumors that are not curable by standard therapy Life expectancy of over 12 weeks Exclusion Criteria: Concurrent therapy with any other investigational drug Known or suspected CNS metastases including leptomeningeal metastases Active bleeding, bleeding diathesis or history of coagulation disorder Uncontrolled diabetes mellitus Active or uncontrolled infections Patients with HIV infections

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Drug: RO5429083<br>* Cohorts receiving multiple escalating doses iv<br>|
| Experimental: B<br> | Drug: RO5429083<br>* Cohorts receiving 89Zr-labelled RO5429083 plus RO5429083, followed by RO5429083 until disease progression<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Arm A: Safety (Incidence of adverse events related to study drug) |  | Until disease progression or unacceptable toxicity (approximately 2 years) | 
| Arm A: Maximum tolerated dose of RO5429083 |  | Until disease progression or unacceptable toxicity (approximately 2 years) | 
| Arm A: Tumor Growth Control Rate |  | Until disease progression or unacceptable toxicity (approximately 2 years) | 
| Arm B: Tissue distribution of RO5429083 assessed by positron emission tomography (PET) |  | Until disease progression or unacceptable toxicity (approximately 2 years) | 
| Arm A: Pharmacokinetics (serum levels of RO5429083) |  | Until disease progression or unacceptable toxicity (approximately 2 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Arm A: Recommended dose of RO5429083 for the extension cohort |  | Until disease progression or unacceptable toxicity (approximately 2 years) | 
| Arm A: Anti-tumor activity of RO5429083 |  | Until disease progression or unacceptable toxicity (approximately 2 years) | 
| Arm B: Target saturation of 89Zr-labelled RO5429083 |  | Until disease progression or unacceptable toxicity (approximately 2 years) |