Trial · NCT00996892
Safety, Tolerability and Pharmacokinetics of Cobimetinib in Combination With Pictilisib in Patients With Locally Advanced or Metastatic Solid Tumors
NCT00996892, Phase 1, Terminated, Genentech, Inc.; results first posted 2016-12-30
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. Safety, Tolerability and Pharmacokinetics of Cobimetinib in Combination With Pictilisib in Patients With Locally Advanced or Metastatic Solid Tumors. Trials, record NCT00996892. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT00996892
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- Safety, Tolerability and Pharmacokinetics of Cobimetinib in Combination With Pictilisib in Patients With Locally Advanced or Metastatic Solid Tumors
- NCT number
- NCT00996892
- Status
- Terminated
- Phases
- Phase 1
- Enrollment
- 178 participants, actual
- Lead sponsor
- Genentech, Inc.
- Conditions
- Solid Tumors
- Interventions
- Cobimetinib, Pictilisib
- First posted
- 2009-10-16
- Last updated
- 2016-12-30
- Results first posted
- 2016-12-30
- Limitations and caveats
- The study was terminated prior to the initiation of Stage 2B and as per changes in planned analysis the data for duration of objective response and PFS were not analyzed.
Source ClinicalTrials.gov
Registered outcomes99
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Number of Participants With Dose-Limiting Toxicities (DLTs) During Dose Escalation Stages 1, 1A and 1B | Cohorts 1-3: Day 1 to Day 35, All other cohorts: Day 1 to Day 28 | DLT was defined as 1 of the following toxicities considered treatment related by Investigator: Grade ≥3 non-hematologic, non-hepatic organ toxicity, excluding the following: Grade 3 nausea, vomiting, or diarrhea that resolved to Grade ≤1 within 7 days, Grade 3 rash or Grade ≥3 fatigue that resolved to Grade ≤2 within 7 days, Grade ≥3 hyperglycemia or lipid profile results that occurred during non-fasting conditions, Grade 3 or 4 elevation of serum creatine phosphokinase levels or Grade 3 non clinically significant (as assessed by Investigator) laboratory abnormality that was asymptomatic; Grade ≥3 febrile neutropenia; Grade ≥4 neutropenia (absolute neutrophil count \<500/microliter) lasting \>5 days; Grade ≥4 thrombocytopenia lasting \>48 hours; Grade ≥4 anemia; Grade ≥3 total bilirubin, hepatic transaminase, alkaline phosphatase, lasting \>72 hours; Grade ≥2 diffusion capacity of the lung for carbon monoxide concomitant with an absolute decrease of ≥20 percentage points from baseline. |
| Primary | Maximum Tolerated Combination Doses of Cobimetinib and Pictilisib During Dose-Escalation Stages 1, 1A and 1B | Cohorts 1-3: Day 1 to Day 35, All other cohorts: Day 1 to Day 28 | MTD was determined (by Investigator) based on the DLTs, as well as adverse events (AEs) in dose-escalation Stages 1, 1A, and 1B that did not meet protocol-defined DLT criteria but indicated intolerability of a given dose combination. Separate combination MTDs were determined for each dose-escalation stage. DLT was defined as 1 of the following toxicities considered treatment related by Investigator: Grade ≥3 non-hematologic, non-hepatic organ toxicity; Grade ≥3 febrile neutropenia; Grade ≥4 neutropenia (absolute neutrophil count \<500/microliter) lasting \>5 days; Grade ≥4 thrombocytopenia lasting \>48 hours; Grade ≥4 anemia; Grade ≥3 total bilirubin, hepatic transaminase, alkaline phosphatase, lasting \>72 hours; Grade ≥2 diffusion capacity of the lung for carbon monoxide concomitant with an absolute decrease of ≥20 percentage points from baseline. |
| Primary | Time of Maximum Concentration (Tmax) of Cobimetinib on Day 3 - Stage 1, Cohorts 1-3 | 0-4 hours pre-cobimetinib (Pr-C) dose, 0.5, 2, 4, 6 hours post-cobimetinib (Po-C) dose on Day 3, Day 4 | |
| Primary | Maximum Plasma Concentration (Cmax) of Cobimetinib on Day 3 - Stage 1, Cohorts 1-3 | 0-4 hours Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Day 3, Day 4 | |
| Primary | Area Under the Concentration-Time Curve From Time 0 to 24 Hours Post-Dose (AUC0-24) of Cobimetinib on Day 3 - Stage 1, Cohorts 1-3 | 0-4 hours Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Day 3, Day 4 | |
| Primary | Tmax of Pictilisib on Day 1 - Stage 1, Cohorts 1-3 | 0-4 hours pre-pictilisib (Pr-P) dose, 0.5, 2, 4, 6 hours post-pictilisib (Po-P) dose on Day 1, Day 2, 0-4 hours Pr-C dose on Day 3 | |
| Primary | Cmax of Pictilisib on Day 1 - Stage 1, Cohorts 1-3 | 0-4 hours Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Day 1, Day 2, 0-4 hours Pr-C dose on Day 3 | |
| Primary | AUC0-24 of Pictilisib on Day 1 - Stage 1, Cohorts 1-3 | 0-4 hours Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Day 1, Day 2, 0-4 hours Pr-C dose on Day 3 | |
| Secondary | Tmax of Cobimetinib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | Cohorts 1-3: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 8, Cycle 1 Days 9, 15, 21; Cohorts 4-6A: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Day 2, 8, 14 | |
| Secondary | Cmax of Cobimetinib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | Cohorts 1-3: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 8, Cycle 1 Days 9, 15, 21; Cohorts 4-6A: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Day 2, 8, 14 |
1 to 10 of 99Source ClinicalTrials.gov
See all 99 registered outcomesOutcomes99
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Number of Participants With Dose-Limiting Toxicities (DLTs) During Dose Escalation Stages 1, 1A and 1B | Cohorts 1-3: Day 1 to Day 35, All other cohorts: Day 1 to Day 28 | Safety-evaluable population included all participants who received at least one dose of study drug. Here, number of participants analyzed = participants who were evaluable for this outcome. | participants | NUMBER |
| PRIMARY | Maximum Tolerated Combination Doses of Cobimetinib and Pictilisib During Dose-Escalation Stages 1, 1A and 1B | Cohorts 1-3: Day 1 to Day 35, All other cohorts: Day 1 to Day 28 | Safety-evaluable population. Here, number of participants analyzed = participants who were evaluable for this outcome and n = participants evaluable for specified categories. | mg | NUMBER |
| PRIMARY | Time of Maximum Concentration (Tmax) of Cobimetinib on Day 3 - Stage 1, Cohorts 1-3 | 0-4 hours pre-cobimetinib (Pr-C) dose, 0.5, 2, 4, 6 hours post-cobimetinib (Po-C) dose on Day 3, Day 4 | Pharmacokinetic (PK) population included all participants who had at least one cobimetinib and pictilisib plasma concentration available. Here, number of participants analyzed = participants who were evaluable for this outcome. | hours | MEDIAN |
| PRIMARY | Maximum Plasma Concentration (Cmax) of Cobimetinib on Day 3 - Stage 1, Cohorts 1-3 | 0-4 hours Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Day 3, Day 4 | PK population. Here, number of participants analyzed = participants who were evaluable for this outcome. | nanograms per milliliter (ng/mL) | GEOMETRIC_MEAN |
| PRIMARY | Area Under the Concentration-Time Curve From Time 0 to 24 Hours Post-Dose (AUC0-24) of Cobimetinib on Day 3 - Stage 1, Cohorts 1-3 | 0-4 hours Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Day 3, Day 4 | PK population. Here, number of participants analyzed = participants who were evaluable for this outcome. | nonograms*hour per milliliter (ng*h/mL) | GEOMETRIC_MEAN |
| PRIMARY | Tmax of Pictilisib on Day 1 - Stage 1, Cohorts 1-3 | 0-4 hours pre-pictilisib (Pr-P) dose, 0.5, 2, 4, 6 hours post-pictilisib (Po-P) dose on Day 1, Day 2, 0-4 hours Pr-C dose on Day 3 | PK population. Here, number of participants analyzed = participants who were evaluable for this outcome. | hours | MEDIAN |
| PRIMARY | Cmax of Pictilisib on Day 1 - Stage 1, Cohorts 1-3 | 0-4 hours Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Day 1, Day 2, 0-4 hours Pr-C dose on Day 3 | PK population. Here, number of participants analyzed = participants who were evaluable for this outcome. | ng/mL | GEOMETRIC_MEAN |
| PRIMARY | AUC0-24 of Pictilisib on Day 1 - Stage 1, Cohorts 1-3 | 0-4 hours Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Day 1, Day 2, 0-4 hours Pr-C dose on Day 3 | PK population. Here, number of participants analyzed = participants who were evaluable for this outcome. | ng*h/mL | GEOMETRIC_MEAN |
| SECONDARY | Tmax of Cobimetinib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | Cohorts 1-3: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 8, Cycle 1 Days 9, 15, 21; Cohorts 4-6A: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Day 2, 8, 14 | PK population. Here, number of participants analyzed = participants who were evaluable for this outcome. | hours | MEDIAN |
| SECONDARY | Cmax of Cobimetinib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | Cohorts 1-3: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 8, Cycle 1 Days 9, 15, 21; Cohorts 4-6A: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Day 2, 8, 14 | PK population. Here, number of participants analyzed = participants who were evaluable for this outcome. | ng/mL | GEOMETRIC_MEAN |
1 to 10 of 99Source ClinicalTrials.gov
See all 99 outcomesResults by group588
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Number of Participants With Dose-Limiting Toxicities (DLTs) During Dose Escalation Stages 1, 1A and 1B | S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | 0 | participants | ||
| Number of Participants With Dose-Limiting Toxicities (DLTs) During Dose Escalation Stages 1, 1A and 1B | S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | 0 | participants | ||
| Number of Participants With Dose-Limiting Toxicities (DLTs) During Dose Escalation Stages 1, 1A and 1B | S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | 0 | participants | ||
| Number of Participants With Dose-Limiting Toxicities (DLTs) During Dose Escalation Stages 1, 1A and 1B | S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | 1 | participants | ||
| Number of Participants With Dose-Limiting Toxicities (DLTs) During Dose Escalation Stages 1, 1A and 1B | S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | 1 | participants | ||
| Number of Participants With Dose-Limiting Toxicities (DLTs) During Dose Escalation Stages 1, 1A and 1B | S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | 0 | participants | ||
| Number of Participants With Dose-Limiting Toxicities (DLTs) During Dose Escalation Stages 1, 1A and 1B | S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib | 0 | participants | ||
| Number of Participants With Dose-Limiting Toxicities (DLTs) During Dose Escalation Stages 1, 1A and 1B | S1A CA: 100 mg Cobimetinib + 130 mg Pictilisib | 0 | participants | ||
| Number of Participants With Dose-Limiting Toxicities (DLTs) During Dose Escalation Stages 1, 1A and 1B | S1A CB: 100 mg Cobimetinib + 180 mg Pictilisib | 0 | participants | ||
| Number of Participants With Dose-Limiting Toxicities (DLTs) During Dose Escalation Stages 1, 1A and 1B | S1A CC: 125 mg Cobimetinib + 130 mg Pictilisib | 0 | participants |
1 to 10 of 588Source ClinicalTrials.gov
See all 588 results by groupParticipant flow300
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Dose-Escalation Stage 1 | STARTED | S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | 4 | |
| Dose-Escalation Stage 1 | STARTED | S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | 3 | |
| Dose-Escalation Stage 1 | STARTED | S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | 3 | |
| Dose-Escalation Stage 1 | STARTED | S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | 9 | |
| Dose-Escalation Stage 1 | STARTED | S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | 11 | |
| Dose-Escalation Stage 1 | STARTED | S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | 10 | |
| Dose-Escalation Stage 1 | STARTED | S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib | 4 | |
| Dose-Escalation Stage 1 | STARTED | S1A CA: 100 mg Cobimetinib + 130 mg Pictilisib | 0 | |
| Dose-Escalation Stage 1 | STARTED | S1A CB: 100 mg Cobimetinib + 180 mg Pictilisib | 0 | |
| Dose-Escalation Stage 1 | STARTED | S1A CC: 125 mg Cobimetinib + 130 mg Pictilisib | 0 |
1 to 10 of 300Source ClinicalTrials.gov
See all 300 participant flowAdverse events6,066
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Anaemia | Blood and lymphatic system disorders | S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | 1 | 4 | |
| other | Anaemia | Blood and lymphatic system disorders | S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | 0 | 3 | |
| other | Anaemia | Blood and lymphatic system disorders | S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | 1 | 3 | |
| other | Anaemia | Blood and lymphatic system disorders | S1 C4/S2 Expansion: 40 mg Cobimetinib + 100 mg Pictilisib | 5 | 43 | |
| other | Anaemia | Blood and lymphatic system disorders | S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | 0 | 11 | |
| other | Anaemia | Blood and lymphatic system disorders | S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | 3 | 10 | |
| other | Anaemia | Blood and lymphatic system disorders | S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib | 0 | 4 | |
| other | Anaemia | Blood and lymphatic system disorders | S1A CA: 100 mg Cobimetinib + 130 mg Pictilisib | 2 | 3 | |
| other | Anaemia | Blood and lymphatic system disorders | S1A CB: 100 mg Cobimetinib + 180 mg Pictilisib | 1 | 3 | |
| other | Anaemia | Blood and lymphatic system disorders | S1A CC: 125 mg Cobimetinib + 130 mg Pictilisib | 0 | 4 |
1 to 10 of 6,066Source ClinicalTrials.gov
See all 6,066 adverse eventsAdverse event totals54
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | ||
| Total, all-cause mortality | S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | ||
| Total, all-cause mortality | S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | ||
| Total, all-cause mortality | S1 C4/S2 Expansion: 40 mg Cobimetinib + 100 mg Pictilisib | ||
| Total, all-cause mortality | S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | ||
| Total, all-cause mortality | S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | ||
| Total, all-cause mortality | S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib | ||
| Total, all-cause mortality | S1A CA: 100 mg Cobimetinib + 130 mg Pictilisib | ||
| Total, all-cause mortality | S1A CB: 100 mg Cobimetinib + 180 mg Pictilisib | ||
| Total, all-cause mortality | S1A CC: 125 mg Cobimetinib + 130 mg Pictilisib |
1 to 10 of 54Source ClinicalTrials.gov
See all 54 adverse event totalsPapers0
The papers the trial lists on ClinicalTrials.gov.
None in this release.
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons0
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
None in this release.
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
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