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

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

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.

Study Overview

• Status: Completed
• Conditions: Neoplasms
• Intervention / Treatment: Drug: RO5429083; Drug: RO5429083

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Paris, France, 75231
  • Toulouse, France, 31059
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
  • Nijmegen, Netherlands, 6500 HB
• United States
  • Texas
    • Houston, Texas, United States, 77030
  • Washington
    • Seattle, Washington, United States, 98109

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: May 18, 2011
• First Submitted That Met QC Criteria: May 20, 2011
• First Posted (Estimate): May 24, 2011

Study Record Updates

• Last Update Posted (Estimate): November 2, 2016
• Last Update Submitted That Met QC Criteria: November 1, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Other Study ID Numbers: BP25385; 2010-021168-13 (EudraCT Number)