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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01605526
First received: May 4, 2012
Last updated: July 7, 2014
Last verified: July 2014
  Purpose

This multicenter, open-label, Phase 1b study will evaluate the safety, pharmacok inetics and efficacy of RO5045337 in combination with doxorubicin in patients wi th soft tissue sarcoma. Cohorts of patients will receive escalating doses of RO5 045337 orally on Days 1-5 (1-3) of each 28-day cycle in combination with doxorub icin 60 mg/m2 intravenously on Day 1 of each cycle for up to 6 cycles.


Condition Intervention Phase
Sarcoma
Drug: RO5045337
Drug: doxorubicin
Phase 1

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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

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 ]

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 ]

Enrollment: 23
Study Start Date: May 2012
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single Arm Drug: 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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01605526

Locations
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
Lyon, France, 69373
Toulouse, France, 31059
Villejuif, France, 94805
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01605526     History of Changes
Other Study ID Numbers: NP28021, 2011-006279-21
Study First Received: May 4, 2012
Last Updated: July 7, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Doxorubicin
Liposomal doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 31, 2014