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

Overview[ - collapse ][ - ]

Purpose 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.
ConditionSarcoma
InterventionDrug: RO5045337
Drug: doxorubicin
PhasePhase 1
SponsorHoffmann-La Roche
Responsible PartyHoffmann-La Roche
ClinicalTrials.gov IdentifierNCT01605526
First ReceivedMay 4, 2012
Last UpdatedApril 7, 2014
Last verifiedApril 2014

Tracking Information[ + expand ][ + ]

First Received DateMay 4, 2012
Last Updated DateApril 7, 2014
Start DateMay 2012
Estimated Primary Completion DateJune 2013
Current Primary Outcome Measures
  • Maximum tolerated dose/dose-limiting toxicities [Time Frame: approximately 12 months] [Designated as safety issue: Yes]
  • Safety: Incidence of adverse events [Time Frame: approximately 12 months] [Designated as safety issue: No]
Current Secondary Outcome Measures
  • Pharmacokinetics of RO5045337 and doxorubicin in combination therapy: Area under the concentration-time curve (AUC) [Time Frame: Pre-dose and up to 72 hours post-dose Days 1 and 5 of Cycle 1] [Designated as safety issue: No]
  • Pharmacodynamics: Serum macrophage inhibitory cytokine-1 (MIC-1) levels [Time Frame: Pre-dose and up to 72 hours post-dose on Days 1 and 5 of Cycle 1] [Designated as safety issue: No]

Descriptive Information[ + expand ][ + ]

Brief TitleA Study of RO5045337 in Combination With Doxorubicin in Patients With Soft Tissue Sarcoma
Official TitleA 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
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.
Detailed DescriptionNot Provided
Study TypeInterventional
Study PhasePhase 1
Study DesignAllocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
ConditionSarcoma
InterventionDrug: RO5045337
Multiple escalating oral doses, Days 1-5 (1-3) of each 28-day cycle, up to 6 cycles
Drug: doxorubicin
60 mg/m2 (75 mg/m2, 50 mg/m2) iv on Day 1 of each 28-day cycle, up to 6 cycles
Study Arm (s)Experimental: Single Arm

Recruitment Information[ + expand ][ + ]

Recruitment StatusCompleted
Estimated Enrollment23
Estimated Completion DateJune 2013
Estimated Primary Completion DateJune 2013
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
- 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 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
GenderBoth
Ages18 Years
Accepts Healthy VolunteersNo
ContactsNot Provided
Location CountriesUnited States, France

Administrative Information[ + expand ][ + ]

NCT Number NCT01605526
Other Study ID NumbersNP28021
Has Data Monitoring CommitteeNot Provided
Information Provided ByHoffmann-La Roche
Study SponsorHoffmann-La Roche
CollaboratorsNot Provided
Investigators Study Director: Clinical Trials Hoffmann-La Roche
Verification DateApril 2014

Locations[ + expand ][ + ]

United States, California
Santa Monica, California, United States, 90403
United States, Massachusetts
Boston, Massachusetts, United States, 02115
United States, New Jersey
Hackensack, New Jersey, United States, 07601
United States, Pennsylvania
Philadelphia, Pennsylvania, United States, 19111
United States, Utah
Salt Lake City, Utah, United States, 84132-0001
France
Bordeaux, France, 33076
France
Lyon, France, 69373
France
Toulouse, France, 31059
France
Villejuif, France, 94805