Clinical trial NCT01383733: A Study of RO5458640 in Patients With Advanced Solid Tumors
Official title: A Phase I Multiple Ascending Dose (MAD) Study of RO5458640, a Humanized Monoclonal Antibody Against the TNF-like Weak Inducer of Apoptosis (TWEAK) Ligand, in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2011-06-28
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This multicenter, open-label, multiple ascending dose study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of RO5458640 in patients with advanced solid tumors. Cohorts of patients will receive ascending doses of RO5458640 intravenously, either weekly or every 2 weeks or every 3 weeks, until disease progression or unacceptable toxicity occurs.


Eligibility criteria: Inclusion Criteria:

* Adult patients, \>/= 18 years of age
* Histologically or cytologically confirmed malignant solid tumors
* Measurable and/or evaluable disease according to RECIST 1.1 criteria
* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
* Adequate bone marrow, liver and renal function

Exclusion Criteria:

* Prior chemotherapy, radiotherapy, or hormonal therapy for cancer within 3 weeks of first study treatment, except for short course palliative radiotherapy for pain
* Antibody therapy or other immunotherapy currently or less than 21 days prior to study treatment
* Current immunosuppressive therapy, including those prescribed for organ transplantation and rheumatologic disease
* Corticoid therapy \> 10 mg/day prednisone or equivalent
* Patients who have not recovered from \> grade 1 (NCI CTCAE) prior adverse events from any cancer therapy, except for alopecia
* Pregnant or breastfeeding women
* Known hypersensitivity to any component of RO5458640 or previous severe hypersensitivity reactions to monoclonal antibody therapy
* History of active seizure disorder
* History of CNS or leptomeningeal metastases, except for clinically stable disease for at least 3 weeks prior to first study drug
* Cardiovascular illness: CVA or MI \< 6 months prior to study, CHF \> NYHA Class 2, QTcF \>480 msec.
* Active infection

Primary outcomes:
measure: Safety: Incidence of adverse events
timeFrame: approximately 2 years
measure: Dose Limiting Toxicity (DLT) according to CTEP Common Terminology Criteria for Adverse Events Version 4.0
timeFrame: approximately 2 years
measure: Maximum Tolerated Dose (MTD)
timeFrame: approximately 2 years
Secondary outcomes:
measure: Pharmacokinetics: area under the concentration - time curve (AUC) on two administration schedules
timeFrame: approximately 2 years
measure: Tumor response according to RECIST criteria
timeFrame: approximately 2 years
measure: Antigenicity: Human anti-human antibody [HAHA] profile
timeFrame: approximately 2 years
Other outcomes:
Locations:
city: Ottawa
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: København Ø
country: Denmark
city: Amsterdam
country: Netherlands
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: