Non-Small Cell Lung Cancer, Metastatic Colorectal Cancer, Metastatic Non Small Cell Lung Cancer, Metastatic Cancers, Melanoma Clinical Trial
Official title:
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
| Verified date | November 2018 |
| Source | Genentech, Inc. |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 24 |
| Est. completion date | December 5, 2016 |
| Est. primary completion date | December 5, 2016 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
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 |
| Country | Name | City | State |
|---|---|---|---|
| United States | University of Colorado | Aurora | Colorado |
| United States | Dana Farber Cancer Institute | Boston | Massachusetts |
| United States | Sarah Cannon Research Institute | Nashville | Tennessee |
| United States | Yale Cancer Center | New Haven | Connecticut |
| United States | Washington University School of Medicine | Saint Louis | Missouri |
| Lead Sponsor | Collaborator |
|---|---|
| Genentech, Inc. |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Number of Participants With Dose-Limiting Toxicities (DLTs) | DLTs include symptoms considered by the investigator to be possibly related to study drug. | 28 days (Cycle 1) | |
| Primary | Percentage of Participants With at Least One Adverse Event | An adverse event is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. | Up to 15 months | |
| Primary | Percentage of Participants With at Least One Adverse Event of Special Interest | 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. | Up to 15 months | |
| Primary | Percentage of Participants With at Least One Serious Adverse Event (SAE) | 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. | Up to 15 months | |
| Primary | Percentage of Participants With Laboratory Abnormalities | 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 |
Up to 15 months | |
| Primary | Mean Change From Baseline in Diastolic Blood Pressure | Baseline, up to 15 months | ||
| Primary | Mean Change From Baseline in Lean Body Mass | Baseline, Day 15 | ||
| Primary | Mean Change From Baseline in Pulse Rate | Baseline, up to 15 months | ||
| Primary | Mean Change From Baseline in Respiratory Rate | Baseline, up to 15 months | ||
| Primary | Mean Change From Baseline in Systolic Blood Pressure | Baseline, up to 15 months | ||
| Primary | Mean Change From Baseline in Temperature | Baseline, up to 15 months | ||
| Primary | Mean Change From Baseline in Weight | Baseline, up to 15 months | ||
| Secondary | Maximum Serum Concentration (Cmax) for GDC-0994 | Up to Day 22 | ||
| Secondary | Median Time to Maximum Serum Concentration (Tmax) for GDC-0994 | Up to Day 22 | ||
| Secondary | Maximum Serum Concentration (Cmax) for Cobimetinib | Up to Day 22 | ||
| Secondary | Median Time to Maximum Serum Concentration (Tmax) for Cobimetinib | Up to Day 22 | ||
| Secondary | Total Exposure (AUC From Time 0 to 24 Hour After Dose) for GDC-0994 | Data are reported for evaluable participants. | 0 to 24 hours post-dose (Up to Day 22) | |
| Secondary | Total Exposure (AUC From Time 0 to 24 Hour After Dose) for Cobimetinib | 0 to 24 hours post-dose (Up to Day 22) | ||
| Secondary | Mean Accumulation Ratio | 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 | ||
| Secondary | Mean Terminal Half-life (t1/2) | Up to day 22 of study | ||
| Secondary | Change From Baseline in Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) | Baseline, Day 15 | ||
| Secondary | Change From Baseline in Tumor Tissue Biomarkers | Up to 15 months |