Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Symptoms and General Pathology

Melanoma

Carcinoma, Non-Small-Cell Lung

Neoplasm Metastasis

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Ravoxertinib

Protein Kinase Inhibitors

Enzyme Inhibitors

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.

Concurrent or intermittent dosing of cobimetinib 20 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.

Concurrent or intermittent dosing of cobimetinib 40 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.

Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.

Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 400 mg for 21 consecutive days, followed by 7 days off.

Concurrent or intermittent dosing of cobimetinib 100 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.

Cobimetinib given concurrently or intermittently with GDC-0994 for 21 consecutive days followed by 7 days off.

Cobimetinib

GDC-0994 given for 21 consecutive days followed by 7 days off, along with concurrent or intermittent dosing of cobimetinib.

GDC-0994

Clinical Trials

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.

A Study of the Safety, Tolerability, and Effects of Cobimetinib and GDC-0994 in Patients With Locally Advanced or Metastatic Solid Tumors

A Phase Ib, Open-Label, Dose-Escalation Study Of The Safety, Tolerability, and Pharmacokinetics of Cobimetinib and GDC-0994 In Patients With Locally Advanced or Metastatic Solid Tumors

DLTs include symptoms considered by the investigator to be possibly related to study drug.

An adverse event is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution.

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.

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.

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

Data are reported for evaluable participants.

Genentech, Inc.

Not Assigned

COB 20 mg + GDC 200 mg

COB 40 mg + GDC 200 mg

COB 80 mg + GDC 200 mg

COB 80 mg + GDC 400 mg

COB 100 mg + GDC 200 mg

Total

Age, Continuous

Sex: Female, Male

Medical Communications

Dermatitis Acneiform

Rash

Diarrhoea

Myocardial infarction

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)

Albumin

Alkaline Phosphatase

SGPT/ALT

SGOT/AST

Calcium

Creatinine

Blood Glucose, Fasting

Gamma Glutamyl Transferase

Glucose

Hemoglobin

Lymphocytes, Absolute

Magnesium

Phosphorus

Platelets

Potassium

Sodium

Bilirubin

Uric Acid

White Blood Cell Count

All participants. Data are reported for evaluable participants.

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

Day 1

Steady State

Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 300 mg for 21 consecutive days, followed by 7 days off.

COB 80 mg + GDC 300 mg

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

Data for this measure were not collected.

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

Overall Study

Spots Global Cancer Trial Database for A Study of the Safety, Tolerability, and Effects of Cobimetinib and GDC-0994 in Patients With Locally Advanced or Metastatic Solid Tumors

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial