Colorectal Cancer, Ovarian Cancer
Conditions
Brief summary
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.
Interventions
DRUGRO5323441
cohorts receiving multiple doses iv
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| RO5323441 concentration - pharmacodynamic effect relationship using DCE-MRI | up to 19.5 months |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Feasibility of within-patient dose escalation | from baseline to Day 127 (+/-3) |
| 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 |
| Pharmacokinetics: maximum and trough concentrations of RO5323441 | up to 19.5 months |
Countries
Belgium, Spain, United Kingdom
Outcome results
None listed