Phase 1
Completed N=36
Study of Cobimetinib in Participants With Solid Tumors
Source: ClinicalTrials.gov NCT00467779 ↗Enrolled (actual)
36
Serious AEs
41.2%
Results posted
Jul 2016
Primary outcomePrimary: Stage 1 and 1A: Number of Participants With Dose Limiting Toxicities (DLTs) — 0; 0; 0; 0 participants
Summary
This non-randomized, open-label, study will determine the highest safe dose of cobimetinib, how often it should be taken, how well participants with cancer tolerate cobimetinib and will assess the pharmacokinetic effect of midazolam and dextromethorphan on the study drug.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Stage 1 and 1A: Number of Participants With Dose Limiting Toxicities (DLTs) |
0; 0; 0; 0; 0; 1 | — |
| PRIMARY Stage 1: Maximum Tolerated Dose (MTD) of Cobimetinib in 21/7 Schedule |
60 | — |
| PRIMARY Stage 1A: MTD of Cobimetinib in 14/14 Schedule |
100 | — |
| PRIMARY Stage 1: Maximum Observed Concentration (Cmax) of Cobimetinib at Day 1, Cycle 1 |
4.51; 6.92; 18.3; 18.8; 30.8; 71.7 | — |
| PRIMARY Stage 1: Area Under the Plasma Cobimetinib Concentration Curve From Time 0 to 24 Hours (AUC 0-24) Day 1, Cycle 1 |
56.2; 68.0; 203.0; 242.0; 440.0; 785.0 | — |
| PRIMARY Stage 1: Time to Maximum Concentration (Tmax) of Cobimetinib at Day 1, Cycle 1 |
2.0; 1.0; 1.5; 3.0; 4.0; 2.5 | — |
| SECONDARY Stage 1: Tmax of Cobimetinib at Steady State |
4.0; 1.0; 2.25; 4.0; 3.0; 2.0 | — |
| SECONDARY Stage 1: AUC 0-24 of Cobimetinib at Steady State |
202.0; 288.0; 411.0; 763.0; 886.0; 5370.0 | — |
| SECONDARY Stage 1: AUC 0-24/D of Cobimetinib at Steady State |
62.4; 34; 28.2; 76.3; 44.3; 134 | — |
| SECONDARY Stage 1: Accumulation Ratio of Cobimetinib at Steady State |
3.56; 3.66; 2.65; 3.23; 2.96; 3.61 | — |
| SECONDARY Stage 1: Apparent Clearance of Cobimetinib at Steady State |
22.4; 34.0; 37.1; 13.5; 22.6; 14.0 | — |
| SECONDARY Stage 1: Half-Life (t1/2) of Cobimetinib at Steady State |
80.0; 64.0; 47.8; 66.0; 50.5; 41.3 | — |
| SECONDARY Stage 1: Cmax of Cobimetinib at Steady State |
13.5; 19.8; 28.7; 53.0; 54.7; 341.0 | — |
| SECONDARY Stage 1A: Tmax of Cobimetinib at Cycle 1 Day 1 |
3.0; 4.0; 3.5; 2.5 | — |
| SECONDARY Stage 1A: Cmax of Cobimetinib at Cycle 1 Day 1 |
78.4; 167.0; 258.0; 533.0 | — |
| SECONDARY Stage 1A: AUC 0-24 of Cobimetinib at Cycle 1 Day 1 |
1140; 2130; 4020; 7190 | — |
| SECONDARY Stage 1A: t1/2 of Cobimetinib at Steady State |
59.4; 44.1; 51.6; 47.7 | — |
| SECONDARY Stage 1A: Tmax of Cobimetinib at Steady State |
2.0; 2.0; 3; 6 | — |
| SECONDARY Stage 1A: Apparent Clearance of Cobimetinib at Steady State |
25.1; 14.9; 21.9; 6.9 | — |
| SECONDARY Stage 1A: Accumulation Ratio of Cobimetinib at Steady State |
2.32; 3.14; 2.6; 5.15 | — |
| SECONDARY Stage 1A: AUC 0-24 of Cobimetinib at Steady State |
2990.0; 6740.0; 11500.0; 21500.0 | — |
| SECONDARY Stage 1A: AUC 0-24/D of Cobimetinib at Steady State |
49.8; 84.2; 115.0; 172.0 | — |
| SECONDARY Stage 1A: Cmax of Cobimetinib at Steady State |
180.0; 494.0; 640.0; 1160.0 | — |
| SECONDARY Stage 2: Cmax of Cobimetinib at Cycle 1 Day 1 |
184.0 | — |
| SECONDARY Stage 2:AUC 0-24 of Cobimetinib at Cycle 1 Day 1 |
3060.0 | — |
| SECONDARY Stage 2: Tmax of Cobimetinib at Cycle 1 Day 1 |
3.0 | — |
| SECONDARY Stage 2: Tmax of Cobimetinib at Steady State |
4.0 | — |
| SECONDARY Stage 2: AUC 0-24 of Cobimetinib at Steady State |
10200.0 | — |
| SECONDARY Stage 2: AUC 0-24/D of Cobimetinib at Steady State |
102.0 | — |
| SECONDARY Stage 2: Accumulation Ratio of Cobimetinib at Steady State |
2.5 | — |
| SECONDARY Stage 2: Apparent Clearance of Cobimetinib at Steady State |
9.8 | — |
| SECONDARY Stage 2:Half-Life of Cobimetinib at Steady State |
53.4 | — |
| SECONDARY Stage 2A: AUC 0-24/D of Cobimetinib at Steady State |
84.8 | — |
| SECONDARY Stage 2A: Accumulation Ratio of Cobimetinib at Steady State |
2.3 | — |
| SECONDARY Stage 2A: Apparent Clearance of Cobimetinib at Steady State |
11.8 | — |
| SECONDARY Stage 2A: Half-Life of Cobimetinib at Steady State |
42.7 | — |
| SECONDARY Stage 2A: Tmax of Cobimetinib at Steady State |
3.0 | — |
| SECONDARY Stage 2A: Cmax of Cobimetinib at Steady State |
315.0 | — |
| SECONDARY Stage III: Cmax of Dextromethorphan |
3.44; 3.16 | — |
| SECONDARY Stage III: AUC 0-24 of Dextromethorphan |
24.8; 25.8 | — |
| SECONDARY Stage III: AUC 0-inf of Dextromethorphan |
29.1; 18.9 | — |
| SECONDARY Stage III: Cmax of Midazolam |
11.5; 10.9 | — |
| SECONDARY Stage III: AUC0-24 of Midazolam |
33.0; 33.4 | — |
| SECONDARY Stage III: AUC0-inf of Midazolam |
34.9; 35.7 | — |
Eligibility Criteria
Inclusion Criteria
- Histologically confirmed solid tumor that is metastatic or unresectable, and for which standard curative or palliative measures do not exist or are no longer effective, and there are no known therapies to prolong survival
- Disease that is measurable according to Response Evaluation Criteria in Solid Tumors (RECIST)
- Adequate organ and marrow function
- Sexually active participants must use medically acceptable methods of contraception during the course of the study and at least 11 days after the last dose of study treatment
- Female participants of childbearing potential must have a negative serum pregnancy test at screening
- No other history of/or ongoing malignancy that would potentially interfere with the interpretation of the pharmacodynamic or efficacy assays
Exclusion Criteria
- Anticancer treatment (e.g., chemotherapy, radiotherapy, cytokines, or hormones) within 28 days (6 weeks for nitrosoureas or mitomycin C, or 14 days for hormonal therapy or kinase inhibitors) before the first dose of study drug
- The participant has not recovered to Grade </=1 from adverse events (AEs) or to within 10% of baseline values due to investigational or other agents administered more than 28 days prior to study enrollment
- The participant has received another investigational agent within 28 days of the first dose of study drug
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, diabetes, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia
- The participant is pregnant or breastfeeding
- The participant is known to be positive for the human immunodeficiency virus (HIV)
- Allergy or hypersensitivity to components of the cobimetinib formulation
Data sourced from ClinicalTrials.gov (NCT00467779). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.