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| ID | Type | Description | Link |
|---|---|---|---|
| 2011-002767-15 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| RO5503781 | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Melbourne | Victoria | 3000 | Australia | |||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34180037 | Derived | 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. |
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| ID | Term |
|---|---|
| D009369 | Neoplasms |
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| 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 |
| Pharmacodynamics: p21 Levels in Tumor as Measured by Immunohistochemistry | 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]) |
| Pharmacodynamics: Tumor suppressor gene (p53) Levels in Tumor as Measured by Immunohistochemistry | 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]) |
| Pharmacodynamics: Murine Double Minute 2 (MDM2) Levels in Tumor as Mesured by Reverse transcription polymerase chain reaction (RT-PCR) | 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]) |
| Pharmacodynamics: Ki-67 Levels in Tumor as Measured by Immunohistochemistry | 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]) |
| Pharmacodynamics: Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) Levels in Tumor as Measured by Immunohistochemistry | 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]) |
| Progression Free Survival (PFS) According to Cheson Criteria | andomization 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]) |
| Pharmacodynamics: p53 Mutation Status in Tumor as Measured by AmpliChip p53 Test | 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]) |
| Pharmacodynamics: Mouse Double Minute 2 Homolog (MDM2) Gene Copy Number in Tumor as Measured by in situ Hybridization | 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]) |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) | Sch A: PrD (0 hour), 1, 2, 3, 4, 6, 8, 12 hours PoD on Day 1, 15; PrD 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 |
| Food-Effect: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) | PrD (0 hour), 1, 2, 3, 4, 6, 8 and 12 hours PoD on Day 1, 8, 15; on Day 2, 3, 4/5, 6/7, 9, 10, 11/12, 13/14, 16, 17, 18/19, 20/21, 22 |
| Area Under the Curve from Time Zero to end of dosing interval (AUCtau) | Sch A: PrD (0 hour), 1, 2, 3, 4, 6, 8, 12 hours PoD on Day 1, 15; PrD 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 |
| Food-Effect: Area Under the Curve From Time Zero to Extrapolated 168 hours [AUC(0-168)] | Prd (0 hour), 1, 2, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 8, 15; on Day 2, 3, 4/5, 6/7, 9, 10, 11/12, 13/14, 16, 17, 18/19, 20/21, 22 |
| Maximum Observed Plasma Concentration (Cmax) | Sch A: PrD (0 hour), 1, 2, 3, 4, 6, 8, 12 hours PoD on Day 1, 15; PrD 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 |
| Food-Effect: Maximum Observed Plasma Concentration (Cmax) | PrD (0 hour), 1, 2, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 8, 15; on Day 2, 3, 4/5, 6/7, 9, 10, 11/12, 13/14, 16, 17, 18/19, 20/21, 22 |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | Sch A: PrD (0 hour), 1, 2, 3, 4, 6, 8, 12 hours PoD on Day 1, 15; PrD 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 |
| Food-Effect: Time to Reach Maximum Observed Plasma Concentration (Tmax) | PrD (0 hour), 1, 2, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 8, 15; on Day 2, 3, 4/5, 6/7, 9, 10, 11/12, 13/14, 16, 17, 18/19, 20/21, 22 |
| Plasma Decay Half-Life (t1/2) | Sch A: PrD (0 hour), 1, 2, 3, 4, 6, 8, 12 hours PoD on Day 1, 15; PrD 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 |
| Food-Effect: Plasma Decay Half-Life (t1/2) | PrD (0 hour), 1, 2, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 8, 15; on Day 2, 3, 4/5, 6/7, 9, 10, 11/12, 13/14, 16, 17, 18/19, 20/21, 22 |
| Terminal Elimination Rate Constant (Kel) | Sch A: PrD (0 hour), 1, 2, 3, 4, 6, 8, 12 hours PoD on Day 1, 15; PrD 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 |
| Food-Effect: Terminal Elimination Rate Constant (Kel) | PrD (0 hour), 1, 2, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 8, 15; on Day 2, 3, 4/5, 6/7, 9, 10, 11/12, 13/14, 16, 17, 18/19, 20/21, 22 |
| Apparent Oral Clearance (CL/F) | Sch A: PrD (0 hour), 1, 2, 3, 4, 6, 8, 12 hours PoD on Day 1, 15; PrD 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 |
| Apparent Volume of Distribution (Vz/F) | Sch A: PrD (0 hour), 1, 2, 3, 4, 6, 8, 12 hours PoD on Day 1, 15; PrD 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 |
| Percentage of Participants With Objective Response [Complete Response (CR) plus Partial Response(PR)] According to Cheson Criteria | 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]) |
| Pharmacodynamics: Macrophage Inhibitory Cytokine 1 (MIC-1) Levels in Blood as Measured by Enzyme-linked Immunosorbent Assay (ELISA) | Sch A: PrD (0 hour), 1, 2, 3, 4, 6, 8, 12 hours PoD on Day 1, 15; PrD 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 |
| Hamilton |
| Ontario |
| L8V 5C2 |
| Canada |
| Toronto | Ontario | M5G 2M9 | Canada |
| Montreal | Quebec | H3T 1E2 | Canada |
| Bordeaux | 33076 | France |
| Lyon | 69373 | France |
| Groningen | 9713 GZ | Netherlands |
| Seoul | 110-744 | South Korea |