Clinical trial NCT01148758: A Dose-finding Study of RO5323441 in Patients With Metastatic Treatment-Refractory Colorectal or Ovarian Cancer
Official title: Open-label, Exploratory, Pharmacodynamic (PD) Dose-finding Study of Intravenous RO5323441 in Patients With Metastatic Treatment-refractory Colorectal and Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Colorectal Cancer, Ovarian Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2010-06-22
Enrollment: 7
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: RO5323441 concentration - pharmacodynamic effect relationship using DCE-MRI
timeFrame: up to 19.5 months
Secondary outcomes:
measure: Feasibility of within-patient dose escalation
timeFrame: from baseline to Day 127 (+/-3)
measure: Additional DCE-MRI effects (time-course of DCE-MRI effects, test-retest reproducibility)
timeFrame: up to 19.5 months
measure: Candidate biomarkers associated with PD effect of RO5323441
timeFrame: up to 19.5 months
measure: Pharmacokinetics: maximum and trough concentrations of RO5323441
timeFrame: up to 19.5 months
measure: Safety and tolerability: Adverse events, vital signs, laboratory parameters
timeFrame: up to 19.5 months
measure: Efficacy: ORR, duration of response, progression-free survival according to RECIST criteria, CTI/MRI assessments
timeFrame: up to 19.5 months
Other outcomes:
Locations:
city: Leuven
country: Belgium
city: Barcelona
country: Spain
city: Manchester
country: United Kingdom
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: