A Study of RO5045337 in Combination With Doxorubicin in Patients With Soft Tissue Sarcoma

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Sarcoma

Intervention / Treatment
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* Drug: RO5045337
* Drug: doxorubicin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Arm<br> | Drug: RO5045337<br>* Multiple escalating oral doses, Days 1-5 (1-3) of each 28-day cycle, up to 6 cycles<br>Drug: doxorubicin<br>* 60 mg/m2 (75 mg/m2, 50 mg/m2) iv on Day 1 of each 28-day cycle, up to 6 cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose/dose-limiting toxicities |  | approximately 12 months | 
| Safety: Incidence of adverse events |  | approximately 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 |