Clinical trial NCT01605526: A Study of RO5045337 in Combination With Doxorubicin in Patients With Soft Tissue Sarcoma
Official title: A Multi-center, Open-label Phase IB Study of Escalating Doses of RO5045337, an Oral Small Molecule MDM2 Antagonist, in Combination With Doxorubicin in Patients With Soft Tissue Sarcoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Sarcoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2012-05-25
Enrollment: 23
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, 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.


Eligibility criteria: 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

Primary outcomes:
measure: Maximum tolerated dose/dose-limiting toxicities
timeFrame: approximately 12 months
measure: Safety: Incidence of adverse events
timeFrame: approximately 12 months
Secondary outcomes:
measure: Pharmacokinetics of RO5045337 and doxorubicin in combination therapy: Area under the concentration-time curve (AUC)
timeFrame: Pre-dose and up to 72 hours post-dose Days 1 and 5 of Cycle 1
measure: Pharmacodynamics: Serum macrophage inhibitory cytokine-1 (MIC-1) levels
timeFrame: Pre-dose and up to 72 hours post-dose on Days 1 and 5 of Cycle 1
Other outcomes:
Locations:
city: Santa Monica
country: United States
state: California
city: Boston
country: United States
state: Massachusetts
city: Hackensack
country: United States
state: New Jersey
city: Philadelphia
country: United States
state: Pennsylvania
city: Salt Lake City
country: United States
state: Utah
city: Bordeaux
country: France
city: Lyon
country: France
city: Toulouse
country: France
city: Villejuif
country: France
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: