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

Roche

Status and phase: Completed; Phase 1

Conditions: Neoplasms

Treatments: Drug: RO5503781

Study type: Interventional

Funder types: Industry

Identifiers

NCT01462175

2011-002767-15 (EudraCT Number)

NP27872

Details and patient eligibility

About

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.

Enrollment: 99 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

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 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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99 participants in 2 patient groups

Schedule A: RO5503781 QW

Experimental group

Description:

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.

Treatment:

Drug: RO5503781

Schedule B: RO5503781 QD

Experimental group

Description:

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

Treatment:

Drug: RO5503781