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

Sarcoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01605526
• Other study ID #: NP28021
• Secondary ID: 2011-006279-21
• Status: Completed
• Phase: Phase 1
• First received: May 4, 2012
• Last updated: November 1, 2016
• Start date: May 2012
• Est. completion date: June 2013

Study information

• Verified date: November 2016
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: June 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Sarcoma

Intervention

Drug:
• RO5045337
Multiple escalating oral doses, Days 1-5 (1-3) of each 28-day cycle, up to 6 cycles
• doxorubicin
60 mg/m2 (75 mg/m2, 50 mg/m2) iv on Day 1 of each 28-day cycle, up to 6 cycles

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose/dose-limiting toxicities		approximately 12 months	Yes
Primary	Safety: Incidence of adverse events		approximately 12 months	No
Secondary	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	No
Secondary	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	No