TriangleNCT02457793 · REGISTRY CONDITION SEARCH
A Study of the Safety, Tolerability, and Effects of Cobimetinib and GDC-0994 in Patients With Locally Advanced or Metastatic Solid Tumors
Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.
- Phase
- PHASE1
- Status at capture
- COMPLETED
- Registry last update
- 2018-11-20
This is a two-stage dose-escalation study to assess the safety, tolerability and effects of oral dosing of cobimetinib and GDC-0994 administered in combination in patients with histologically confirmed, locally advanced, or metastatic solid tumors for which standard therapies either do not exist or have proven ineffective or intolerable.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Number of Participants With Dose-Limiting Toxicities (DLTs)
Percentage of Participants With at Least One Adverse Event
Percentage of Participants With at Least One Adverse Event of Special Interest
Percentage of Participants With at Least One Serious Adverse Event (SAE)
Percentage of Participants With Laboratory Abnormalities
Mean Change From Baseline in Diastolic Blood Pressure
Mean Change From Baseline in Lean Body Mass
Mean Change From Baseline in Pulse Rate
Mean Change From Baseline in Respiratory Rate
Mean Change From Baseline in Systolic Blood Pressure
Mean Change From Baseline in Temperature
Mean Change From Baseline in Weight
Maximum Serum Concentration (Cmax) for GDC-0994
Median Time to Maximum Serum Concentration (Tmax) for GDC-0994
Maximum Serum Concentration (Cmax) for Cobimetinib
Median Time to Maximum Serum Concentration (Tmax) for Cobimetinib
Total Exposure (AUC From Time 0 to 24 Hour After Dose) for GDC-0994
Total Exposure (AUC From Time 0 to 24 Hour After Dose) for Cobimetinib
Mean Accumulation Ratio
Mean Terminal Half-life (t1/2)
Change From Baseline in Fluorodeoxyglucose Positron Emission Tomography (FDG-PET)
Change From Baseline in Tumor Tissue Biomarkers
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- Inclusion Criteria: * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Histologically or cytologically documented, locally advanced or metastatic solid tumors for which standard therapy either does not exist or has proven ineffective or intolerable * Evaluable disease or disease measurable * Life expectancy \> or = 12 weeks * Adequate hematologic and end organ function * For female patients of childbearing potential and male patients with partners of childbearing potential, use of an effective form of contraception with continued use for study duration and up to 3 months or more following discontinuation of treatment drug * Fluorodeoxyglucose positron emission tomography (FDG-PET) avid disease on baseline scan For enrollment in part 2, patients must meet all of the following: * Measurable disease * No more than four prior systemic therapies for locally advanced or metastatic cancer Exclusion Criteria: * History of prior significant toxicity from another MEK inhibitor or ERK inhibitor requiring discontinuation of treatment * Evidence of visible retinal pathology as assessed by ophthalmologic examination that is considered a risk factor for retinal vein thrombosis * History of glaucoma * Intraocular pressure \> 21 mmHg as measured by tonometry * Predisposing factors to retinal vein occlusion (RVO) * History of RVO, neurosensory retinal detachment, or neovascular macular degeneration * Allergy or hypersensitivity to components of the cobimetinib or GDC-0994 formulation * Palliative radiotherapy within 2 weeks prior to first dose of study-drug treatment in Cycle 1 * Experimental therapy within 4 weeks prior to first dose of study-drug treatment in Cycle 1 * Major surgical procedure or significant traumatic injury within 4 weeks prior to the first dose of study-drug treatment in Cycle 1, or anticipation of the need for major surgery during the course of study treatment * Anti-cancer therapy within 28 days prior to the first dose of study-drug treatment in Cycle 1 * Current severe, uncontrolled systemic disease * History of clinically significant cardiac dysfunction * History of symptomatic congestive heart failure or serious cardiac arrhythmia requiring treatment * History of myocardial infarction within 6 months prior to the first dose of study-drug treatment in Cycle 1 * History of congenital long QT syndrome or QTc \> 470 msec * LVEF * History of malabsorption or other condition that would interfere with enteral absorption * Clinically significant history of liver disease, current alcohol abuse, or current known active infection with HIV, hepatitis B virus, or hepatitis C virus * Any condition requiring warfarin or thrombolytic anticoagulants * Active autoimmune disease * Uncontrolled ascites requiring weekly large volume paracentesis for 3 consecutive weeks prior to enrollment * Pregnancy, lactation, or breastfeeding * Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms * No other history of or ongoing malignancy that would potentially interfere with the interpretation of the Pharmacodynamic (PD) or efficacy assays
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- One participant was assigned to receive intermittent cobimetinib 80 milligrams (mg) + GDC 0994 200 mg) and did receive study drug. However, the participant diary was not returned, and the site was unable to document study dose administration.
- intervention Names
- Drug: Cobimetinib
- Drug: GDC-0994
- label
- Not assigned
- type
- EXPERIMENTAL
- description
- Concurrent or intermittent dosing of cobimetinib 20 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
- intervention Names
- Drug: Cobimetinib
- Drug: GDC-0994
- label
- COB 20 mg + GDC 200 mg
- type
- EXPERIMENTAL
- description
- Concurrent or intermittent dosing of cobimetinib 40 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
- intervention Names
- Drug: Cobimetinib
- Drug: GDC-0994
- label
- COB 40 mg + GDC 200 mg
- type
- EXPERIMENTAL
- description
- Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
- intervention Names
- Drug: Cobimetinib
- Drug: GDC-0994
- label
- COB 80 mg + GDC 200 mg
- type
- EXPERIMENTAL
- description
- Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 400 mg for 21 consecutive days, followed by 7 days off.
- intervention Names
- Drug: Cobimetinib
- Drug: GDC-0994
- label
- COB 80 mg + GDC 400 mg
- type
- EXPERIMENTAL
- description
- Concurrent or intermittent dosing of cobimetinib 100 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
- intervention Names
- Drug: Cobimetinib
- Drug: GDC-0994
- label
- COB 100 mg + GDC 200 mg
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- COB 100 mg + GDC 200 mg
- COB 20 mg + GDC 200 mg
- COB 40 mg + GDC 200 mg
- COB 80 mg + GDC 200 mg
- COB 80 mg + GDC 400 mg
- Not assigned
- description
- Cobimetinib given concurrently or intermittently with GDC-0994 for 21 consecutive days followed by 7 days off.
- name
- Cobimetinib
- type
- DRUG
- arm Group Labels
- COB 100 mg + GDC 200 mg
- COB 20 mg + GDC 200 mg
- COB 40 mg + GDC 200 mg
- COB 80 mg + GDC 200 mg
- COB 80 mg + GDC 400 mg
- Not assigned
- description
- GDC-0994 given for 21 consecutive days followed by 7 days off, along with concurrent or intermittent dosing of cobimetinib.
- name
- GDC-0994
- type
- DRUG
Study design
- allocation
- NON_RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 24
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- DLTs include symptoms considered by the investigator to be possibly related to study drug.
- measure
- Number of Participants With Dose-Limiting Toxicities (DLTs)
- time Frame
- 28 days (Cycle 1)
- description
- An adverse event is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution.
- measure
- Percentage of Participants With at Least One Adverse Event
- time Frame
- Up to 15 months
- description
- AESIs were graded per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v4.0. AESIs included the following: Grade ≥ 1 retinal vein occlusion; Grade ≥ 2 visual disturbances (including events suggestive of serous retinopathy); Grade ≥ 3 rash for \> 7 days; Grade ≥ 3 diarrhea for \> 3 days; Grade ≥ 2 left ventricular ejection fraction (LVEF) decrease; Grade 3 hepatotoxicity; any dose-limiting toxicity (DLT); cases of potential drug-induced liver injury that include an elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) (AST \> 3 × baseline value \[and above the upper limit of normal, ULN\]) in combination with either an elevated bilirubin ( \> 2 × ULN) or clinical jaundice; or suspected transmission of an infectious agent by either study drug.
- measure
- Percentage of Participants With at Least One Adverse Event of Special Interest
- time Frame
- Up to 15 months
- description
- A SAE is any experience that: results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is medically significant.
- measure
- Percentage of Participants With at Least One Serious Adverse Event (SAE)
- time Frame
- Up to 15 months
- description
- Laboratory abnormalities were graded per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v4.0. SGPT/ALT - serum glutamic-pyruvic transaminase/alanine aminotransferase; SGOT/AST - serum glutamic oxaloacetic transaminase/aspartate aminotransferase
- measure
- Percentage of Participants With Laboratory Abnormalities
- time Frame
- Up to 15 months
- measure
- Mean Change From Baseline in Diastolic Blood Pressure
- time Frame
- Baseline, up to 15 months
- measure
- Mean Change From Baseline in Lean Body Mass
- time Frame
- Baseline, Day 15
- measure
- Mean Change From Baseline in Pulse Rate
- time Frame
- Baseline, up to 15 months
- measure
- Mean Change From Baseline in Respiratory Rate
- time Frame
- Baseline, up to 15 months
- measure
- Mean Change From Baseline in Systolic Blood Pressure
- time Frame
- Baseline, up to 15 months
- measure
- Mean Change From Baseline in Temperature
- time Frame
- Baseline, up to 15 months
- measure
- Mean Change From Baseline in Weight
- time Frame
- Baseline, up to 15 months
- secondary Outcomes
- measure
- Maximum Serum Concentration (Cmax) for GDC-0994
- time Frame
- Up to Day 22
- measure
- Median Time to Maximum Serum Concentration (Tmax) for GDC-0994
- time Frame
- Up to Day 22
- measure
- Maximum Serum Concentration (Cmax) for Cobimetinib
- time Frame
- Up to Day 22
- measure
- Median Time to Maximum Serum Concentration (Tmax) for Cobimetinib
- time Frame
- Up to Day 22
- description
- Data are reported for evaluable participants.
- measure
- Total Exposure (AUC From Time 0 to 24 Hour After Dose) for GDC-0994
- time Frame
- 0 to 24 hours post-dose (Up to Day 22)
- measure
- Total Exposure (AUC From Time 0 to 24 Hour After Dose) for Cobimetinib
- time Frame
- 0 to 24 hours post-dose (Up to Day 22)
- measure
- Mean Accumulation Ratio
- time Frame
- Pre-dose Day 1 Cycle 1, 2, 3, Day 18, 21 Cycle 1; post-dose 0.5, 1, 2, 3, 4, 6 hours Day 1, 18, 21 Cycle 1; Day 2, 15, 19, 22, Cycle 1
- measure
- Mean Terminal Half-life (t1/2)
- time Frame
- Up to day 22 of study
- measure
- Change From Baseline in Fluorodeoxyglucose Positron Emission Tomography (FDG-PET)
- time Frame
- Baseline, Day 15
- measure
- Change From Baseline in Tumor Tissue Biomarkers
- time Frame
- Up to 15 months
Full study description
- brief Summary
- This is a two-stage dose-escalation study to assess the safety, tolerability and effects of oral dosing of cobimetinib and GDC-0994 administered in combination in patients with histologically confirmed, locally advanced, or metastatic solid tumors for which standard therapies either do not exist or have proven ineffective or intolerable.
Source references
Source notices and limitations
Discovery and provenance
- release id
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- edge id
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- Small Intestine Cancer
- query disease state id
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- source file
- /Users/arunverma/Documents/ChatGPT/Cancer Statistics Website/research-data/2026-09-10/clinicaltrials-condition/round-0000/raw/cond-small-intestine-cancer-000.json
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Preserved source evidence · Not medical advice