NCT01462175

Brief Summary

This multicenter, open label, dose-escalating study will evaluate the safety, pharmacokinetics, pharmacodynamics, and efficacy of RO5503781, administered once daily (QD) or once weekly (QW) in participants with advanced malignancies except leukemia. Participants will receive multiple escalating oral doses in two different dosing schedules (Sch) until disease progression or unacceptable toxicity occurs.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
99

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Nov 2011

Typical duration for phase_1

Geographic Reach
5 countries

8 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 27, 2011

Completed
4 days until next milestone

First Posted

Study publicly available on registry

October 31, 2011

Completed
1 day until next milestone

Study Start

First participant enrolled

November 1, 2011

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2014

Completed
Last Updated

November 2, 2016

Status Verified

November 1, 2016

Enrollment Period

2.7 years

First QC Date

October 27, 2011

Last Update Submit

November 1, 2016

Conditions

Neoplasms

Outcome Measures

Primary Outcomes (3)

  • Maximum Tolerated Dose (MTD)

    up to 28 days

  • Percentage of Participants With Dose Limiting Toxicities (DLTs)

    up to 28 days

  • Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

    approximately 1.5 years

Secondary Outcomes (29)

  • Plasma Concentration of RO5503781

    Sch A: pre-dose (PrD; 0 hour), 1, 2, 3, 4, 6, 8, 12 hours post-dose (PoD) on Day 1, 15; PrD (0 hour) on Day 8; on Day 2, 3, 4/5, 6/7, 16, 17, 18/19, 20/21, 22; Sch B: PrD (0 hour), 1, 2, 3, 4, 6, 8, 12 hours PoD on Day 1, 5; Day 6, 7, 8/9, 10/11, 12

  • Urine Concentration of RO5503781

    Schedule A and B: Pre-dose, 0-4, 4-8, 8-12, 12-24 hours post-dose on Day 1, Day 2

  • Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST)

    Randomization until progressive disease or death (assessed at baseline and every 8 weeks thereafter until progressive disease, death or end of study [up to approximately 1.5 years])

  • Percentage of Participants With Objective Response [Complete Response (CR) plus Partial Response(PR)] According to Response Evaluation Criteria in Solid Tumors (RECIST)

    Randomization until progressive disease or death (assessed at baseline and every 8 weeks thereafter until progressive disease, death or end of study [up to approximately 1.5 years])

  • Standardized Uptake Value (SUV) obtained from the Positron Emission Tomography With 18-Fluorothymidine [(18F)-FLT-PET) Images

    Baseline, Cycle1 Day 5, Cycle 3 Day 1

  • +24 more secondary outcomes

Study Arms (2)

Schedule A: RO5503781 QW

EXPERIMENTAL

Participants will receive multiple ascending doses of RO5503781 orally once weekly (QW) x 3 followed by 13 days of rest in a 28 days cycle.

Drug: RO5503781

Schedule B: RO5503781 QD

EXPERIMENTAL

Participants will receive multiple ascending doses of RO5503781 orally QD x 5 followed by 13 days of rest in a 28 days cycle.

Drug: RO5503781

Interventions

RO5503781DRUG
Schedule A: RO5503781 QWSchedule B: RO5503781 QD

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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 participants
  • Measurable disease (according to RECIST or Cheson criteria) or evaluable disease prior to administration of study drug
  • Minimum weight of 35 kg and life expectancy of greater than or equal to (\>=) 12 weeks
  • 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 less than or equal to (\<=) 1
  • Adequate renal, hepatic and bone marrow function
  • Participants with stable Central Nervous System (CNS) metastasis and with chronic, stable and rate controlled atrial fibrillation
  • Participants in consideration for the biomarker cohorts or apoptosis imaging cohort must consent and be able to undergo paired biopsies for tumor biomarker analyses
  • Able to participate and willing to give written informed consent and to comply with the study restrictions

You may not qualify if:

  • 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 hormonal therapy within 2 weeks and 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 participants who are currently receiving anti-retroviral treatment
  • Known coagulopathy, platelet disorder or history of non-drug induced thrombocytopenia
  • Participants receiving oral or parenteral anticoagulants/antiplatelet agents; anticoagulant flushes for maintenance of indwelling catheters are allowed
  • Participants with known bone marrow disorder which may interfere with bone marrow recovery
  • Participants with hypersensitivity reaction to 18Fluorothymidine (FLT or 18F) compounds

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (8)

Unknown Facility

Melbourne, Victoria, 3000, Australia

Location

Unknown Facility

Hamilton, Ontario, L8V 5C2, Canada

Location

Unknown Facility

Toronto, Ontario, M5G 2M9, Canada

Location

Unknown Facility

Montreal, Quebec, H3T 1E2, Canada

Location

Unknown Facility

Bordeaux, 33076, France

Location

Unknown Facility

Lyon, 69373, France

Location

Unknown Facility

Groningen, 9713 GZ, Netherlands

Location

Unknown Facility

Seoul, 110-744, South Korea

Location

Related Publications (1)

  • Italiano A, Miller WH Jr, Blay JY, Gietema JA, Bang YJ, Mileshkin LR, Hirte HW, Higgins B, Blotner S, Nichols GL, Chen LC, Petry C, Yang QJ, Schmitt C, Jamois C, Siu LL. Phase I study of daily and weekly regimens of the orally administered MDM2 antagonist idasanutlin in patients with advanced tumors. Invest New Drugs. 2021 Dec;39(6):1587-1597. doi: 10.1007/s10637-021-01141-2. Epub 2021 Jun 28.

    PMID: 34180037DERIVED

MeSH Terms

Conditions

Neoplasms

Study Officials

  • Clinical Trials

    Hoffmann-La Roche

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 27, 2011

First Posted

October 31, 2011

Study Start

November 1, 2011

Primary Completion

July 1, 2014

Study Completion

July 1, 2014

Last Updated

November 2, 2016

Record last verified: 2016-11

Locations

CA(3)FR(2)KR(1)AU(1)NL(1)