A Dose-finding Study of RO5323441 in Patients With Metastatic Treatment-Refractory Colorectal or Ovarian Cancer

Study Overview
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Brief Summary
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This exploratory, open label study will assess the the dose-effect relationship, efficacy and safety of RO5323441 in patients with metastatic treatment-refractory colorectal or ovarian cancer. Cohorts of patients will receive doses of intravenous RO5323441 in the range of 25mg to 3g every 1 or 2 weeks and will undergo serial dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) assessments. In the absence of disease progression and unacceptable toxicity, patients may continue to receive their maximum dose of RO5323441 for a core treatment phase of up to a total of 6 months. Treatment with RO5323441 can be extended at the investigator's discretion until disease progression or unacceptable toxicity occurs. Target sample size is <100.

Official Title
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Open-label, Exploratory, Pharmacodynamic (PD) Dose-finding Study of Intravenous RO5323441 in Patients With Metastatic Treatment-refractory Colorectal and Ovarian Cancer

Conditions
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Colorectal Cancer, Ovarian Cancer

Intervention / Treatment
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* Drug: RO5323441


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients, >/=19 years of age metastatic or unresectable colorectal or ovarian cancer refractory to, or unsuitable for standard therapy presence of tumor lesions suitable for DCE-MRI evaluation WHO performance status 0-1 adequate bone marrow, liver and renal function Exclusion Criteria: patient unsuitable for MRI scanning (e.g. metal implants, pacemaker, claustrophobia, hypersensitivity to DCE-MRI contrast material) brain metastases clinically significant ascites active bleeding, bleeding diathesis, oral anti-vitamin K medication (other than low dose coumarin) or history of coagulation disorders radiation therapy within 3 weeks, or anti-neoplastic therapy <30 days prior to first dose of study drug chronic therapy with systemic steroids or another immunosuppressive agent <2 weeks prior to first dose of study drug treated with bevacizumab in last regimen of systemic therapy

Ages Eligible for Study
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Minimum Age: 19 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: Single Arm<br> | Drug: RO5323441<br>* cohorts receiving multiple doses iv<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RO5323441 concentration - pharmacodynamic effect relationship using DCE-MRI |  | up to 19.5 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of within-patient dose escalation |  | from baseline to Day 127 (+/-3) | 
| Additional DCE-MRI effects (time-course of DCE-MRI effects, test-retest reproducibility) |  | up to 19.5 months | 
| Candidate biomarkers associated with PD effect of RO5323441 |  | up to 19.5 months | 
| Pharmacokinetics: maximum and trough concentrations of RO5323441 |  | up to 19.5 months | 
| Safety and tolerability: Adverse events, vital signs, laboratory parameters |  | up to 19.5 months | 
| Efficacy: ORR, duration of response, progression-free survival according to RECIST criteria, CTI/MRI assessments |  | up to 19.5 months |