A Multiple Ascending Dose Study of R4733 in Patients With Advanced Solid Tumors.

Study Overview
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Brief Summary
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This study will determine the maximum tolerated dose, safety and pharmacokinetic profile of R4733 (RO4929097), administered orally to patients with refractory metastatic or locally advanced solid tumors. The study will assess three different dosing schedules; in one schedule R4733 will be administered 3days on/ 4 days off, in another on days 1-7 of each 21 day cycle, and in a third schedule continuously daily. The starting dose for each dosing regimen will be escalated in subsequent groups of patients after a satisfactory assessment of the safety and tolerability of the previous dose. The anticipated time on study treatment is until disease progression or dose-limiting toxicity, and the target sample size is 100-200 individuals.

Official Title
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Multiple Ascending Dose (MAD) Study of R4733 Administered Orally in Patients With Refractory Metastatic or Locally Advanced Solid Tumors

Conditions
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Neoplasms

Intervention / Treatment
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* Drug: RG4733
* Drug: RG4733
* Drug: RG4733


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients, >=18 years of age; advanced and/or metastatic solid tumor malignancy; measurable or evaluable disease; ECOG performance status 0 or 1. Exclusion Criteria: prior chemotherapy, radiotherapy or immunotherapy within 28 days of first receipt of study drug; prior corticosteroids as anti-cancer therapy within a minimum of 14 days of first receipt of study drug. Dexamethasone may be allowed only as part of the supportive care measures; major surgery within 28 days of first receipt of study drug.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: RG4733<br>* Administered orally at ascending doses to successive cohorts of patients, on a 3 days on/ 4 days off schedule<br>* Other names: RO4929097;|
| Experimental: 2<br> | Drug: RG4733<br>* Administered orally at ascending doses to successive cohorts of patients, on days 1-7 of each 21 day cycle<br>* Other names: RO4929097;|
| Experimental: 3<br> | Drug: RG4733<br>* Administered orally daily at ascending doses to successive cohorts of patients<br>* Other names: RO4929097;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AEs, laboratory parameters. |  | Throughout study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor assessments |  | day 15 cycle 1, at the end of cycle 2 and every 6 weeks thereafter | 
| Pharmacokinetic profile |  | After first dose and last dose (or day 15) of cycles 1 and 2 |