A First-In-Human Study of RO5503781 in Patients With Advanced Malignancies, Except Leukemia

This study has been completed.
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
First received: October 27, 2011
Last updated: July 1, 2016
Last verified: July 2016
This multicenter, open label, dose-escalating study will evaluate the safety, pharmacokinetics, pharmacodynamics and efficacy of RO5503781 in patients with advanced malignancies except leukemia. Patients will receive multiple escalating oral doses in two different dosing schedules. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.

Condition Intervention Phase
Drug: RO5503781
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multi-center, Open Label, First in Human Phase I Dose Escalation Study of Single Agent RO5503781, a Small Molecule MDM2 Antagonist, Administered Orally in Patients With Advanced Malignancies, Except Leukemia

Resource links provided by NLM:

Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD), schedules A + B [ Time Frame: approximately 1.5 years ] [ Designated as safety issue: Yes ]
  • Dose limiting toxicities (DLTs) [ Time Frame: approximately 1.5 years ] [ Designated as safety issue: Yes ]
  • Safety: Incidence of adverse events [ Time Frame: approximately 1.5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pharmacokinetics: blood/urine concentrations [ Time Frame: up to 22 days ] [ Designated as safety issue: No ]
  • Pharmacodynamic assessments (plasma/serum/tumor biomarkers) [ Time Frame: up to 22 days ] [ Designated as safety issue: No ]
  • Clinical response (tumor assessments according to RECIST criteria or Cheson criteria) [ Time Frame: approximately 1.5 years ] [ Designated as safety issue: No ]
  • Food effect on pharmacokinetics: blood levels after administration in fasted vs fed state [ Time Frame: 22 days ] [ Designated as safety issue: No ]

Enrollment: 99
Study Start Date: November 2011
Study Completion Date: July 2014
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A Drug: RO5503781
Multiple ascending doses orally, once weekly x 3 followed by 13 days of rest
Experimental: B Drug: RO5503781
Multiple ascending doses orally, daily x 5 followed by 23 days of rest


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Adult patients, >/= 18 years of age
  • Histologically or cytologically confirmed advanced malignancies, except all forms of leukemia, for which standard curative or palliative measures do not exist, are no longer effective, or are not acceptable to the patient
  • Measurable disease (according to RECIST or Cheson criteria) or evaluable disease prior to administration of study drug
  • Minimum weight of 35 kg
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
  • Acute toxicities from any prior anti-tumor therapy, surgery, or radiotherapy must have resolved to NCT-CTCAE Grade </=1
  • Adequate renal, hepatic and bone marrow function

Exclusion Criteria:

  • History of any form of leukemia except for Stage 0 and 1 chronic lymphocytic leukemia (CLL) not requiring treatment in addition to the underlying solid tumor
  • Use of other investigational agents or having received investigational drugs </= 4 weeks prior to study treatment start
  • History of seizure disorders or unstable CNS metastases
  • Severe and/or uncontrolled cardiovascular disease or disorder
  • Active (acute or chronic) or uncontrolled infection
  • Pregnant or breastfeeding women
  • HIV-positive patients who are currently receiving anti-retroviral treatment
  • Known coagulopathy, platelet disorder or history of non-drug induced thrombocytopenia
  • Patients receiving oral or parenteral anticoagulants/antiplatelet agents; anticoagulant flushes for maintenance of indwelling catheters are allowed
  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: NCT01462175

Australia, Victoria
Melbourne, Victoria, Australia, 3000
Canada, Ontario
Hamilton, Ontario, Canada, L8V 5C2
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Montreal, Quebec, Canada, H3T 1E2
Bordeaux, France, 33076
Lyon, France, 69373
Korea, Republic of
Seoul, Korea, Republic of, 110-744
Groningen, Netherlands, 9713 GZ
Sponsors and Collaborators
Hoffmann-La Roche
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01462175     History of Changes
Other Study ID Numbers: NP27872  2011-002767-15 
Study First Received: October 27, 2011
Last Updated: July 1, 2016
Health Authority: France: Agence Francaise de Securite Sanitaire des Produits de Sante

ClinicalTrials.gov processed this record on July 25, 2016