Sarcoma
Conditions
Brief summary
This multicenter, open-label, Phase 1b study will evaluate the safety, pharmacokinetics and efficacy of RO5045337 in combination with doxorubicin in patients with soft tissue sarcoma. Cohorts of patients will receive escalating doses of RO5045337 orally on Days 1-5 (1-3) of each 28-day cycle in combination with doxorubicin 60 mg/m2 intravenously on Day 1 of each cycle for up to 6 cycles.
Interventions
DRUGRO5045337
Multiple escalating oral doses, Days 1-5 (1-3) of each 28-day cycle, up to 6 cycles
DRUGdoxorubicin
60 mg/m2 (75 mg/m2, 50 mg/m2) iv on Day 1 of each 28-day cycle, up to 6 cycles
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients, \>/= 18 years of age * Histologically or cytologically confirmed soft tissue sarcoma * Evaluable disease according to RECIST version 1.1 criteria * Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 * Eligible for doxorubicin therapy * Acute toxicities from prior anti-tumor therapy, surgery or radiotherapy must have resolved to NCI-CTCAE Grade \</= 1 prior to start of study * Adequate bone marrow, hepatic and renal function * Patients with stable CNS metastases are eligible
Exclusion criteria
* Previous treatment with limiting doses of doxorubicin * Patients receiving any other investigational or commercial agents or therapies administered with the intention to treat their malignancy or other ailment \</= 28 days from Day 1 dosing on study treatment * History of seizure disorders or unstable CNS metastases * Severe and/or uncontrolled medical conditions or other conditions that could affect the participation in the study * Pregnant or breastfeeding women * HIV positive patients who are currently receiving combination anti-retroviral therapy * Patients with known coagulopathy, platelet disorder or history of non-drug induced thrombocytopenia * Patients receiving oral or parenteral anti-coagulants/anti-platelet agents
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum tolerated dose/dose-limiting toxicities | approximately 12 months |
| Safety: Incidence of adverse events | approximately 12 months |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetics of RO5045337 and doxorubicin in combination therapy: Area under the concentration-time curve (AUC) | Pre-dose and up to 72 hours post-dose Days 1 and 5 of Cycle 1 |
| Pharmacodynamics: Serum macrophage inhibitory cytokine-1 (MIC-1) levels | Pre-dose and up to 72 hours post-dose on Days 1 and 5 of Cycle 1 |
Countries
France, United States
Outcome results
None listed