Roche trials database

Trial information

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

Status:

Completed

Protocol number:

BP22909

Sponsor:

Hoffmann-La Roche

Company division:

Pharmaceutical

Official Scientific Title:

Open-label, exploratory, pharmacodynamic (PD) dose-finding study of intravenous RO5323441 in patients with metastatic treatment-refractory colorectal and ovarian cancer

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. Target sample size is 7.

Study phase:

I

Study type:

Interventional; Treatment; Non-randomized; Open label; Single group; Pharmacodynamics study

Conditions:

• Ovarian Cancer
• Colorectal Cancer

Primary outcome:

1. RO5323441 concentration - pharmacodynamic effect relationship using DCE-MRI Time frame: up to 19.5 months

Key secondary outcomes:

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

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

Gender:

Males or Females

Age limits:

Min: 19 years Max: N/A N/A

Accepts healthy volunteers:

No

Anticipated start date:

May, 2010

Trial registration date:

27.01.2010

Date last updated:

10.06.2013

This trial was conducted at the following locations:

Belgium

• LEUVEN

SPAIN

• Barcelona, BARCE

United Kingdom

• MANCHESTER

Link to trial result