Solid Cancers
Conditions
Brief summary
This is an open-label, multicenter, Phase I dose-escalation study to assess the safety, tolerability, and pharmacokinetics of GDC-0623 in patients with locally advanced or metastatic solid tumors. Patients will be enrolled in one of two stages: a dose-escalation stage (Stage I) followed by an expansion stage (Stage II). Stage I will evaluate the safety, tolerability, and pharmacokinetics of increasing doses of GDC-0623 administered orally on a 21 day on/7-day off dosing schedule.
Interventions
DRUGGDC-0623
Repeating oral dose
Sponsors
Genentech, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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 per RECIST * Life expectancy \>= 12 weeks * Adequate hematologic and end organ function * Agreement to use effective form of contraception for the duration of the study * Consent to provide archival tissue * For the cohort expansion stage (Stage II): Patients in this cohort must have had no more than four prior systemic therapies for cancer and must have KRAS mutant CRC (Stage II A and B), pancreatic cancer (Stage IIC, or KRAS mutant NSCLC \[Stage IID\])
Exclusion criteria
* History of prior significant toxicity from a MEK pathway inhibitor requiring discontinuation of treatment * History of parathyroid disorder or history of malignancy-associated hypercalcemia requiring therapy in the last 6 months * History of retinal vein occlusion (RVO) or predisposing factors to RVO, including uncontrolled hypertension, uncontrolled diabetes, uncontrolled hyperlipidemia, and coagulopathy * Evidence of visible retinal pathology considered a risk factor for retinal vein thrombosis * History of glaucoma * Palliative radiotherapy, experimental therapy, or anti-cancer therapy or major surgical procedure within a specified timeframe prior to first dose of study drug * Current severe, uncontrolled systemic disease * History of clinically significant cardiac dysfunction * History of active gastrointestinal bleeding within 6 months prior to screening * Clinically significant history of liver disease, current alcohol abuse, or current known active infection with HIV, or hepatitis B or C virus * Active autoimmune disease * Uncontrolled ascites * Pregnancy, lactation, or breastfeeding * Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms * For the Exploratory PK Cohorts (Stage IB and Stage IC): Patients who have a history of or ongoing gastro-esophageal reflux disease or peptic ulcer, or who have gastric pathology or history of gastric surgery which could affect absorption of GDC-0623 from the stomach, will be excluded from these cohorts
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence and nature of dose-limiting toxicities (DLTs) | Through study completion or early discontinuation |
| Incidence, nature, and severity of adverse events and serious adverse events, graded according to NCI CTCAE, v4.0 | Through study completion or early discontinuation |
| Pharmacokinetic parameters of GDC-0623 (total exposure, maximum and minimum plasma concentrations, time to maximum plasma concentration, elimination half-life) | Through study completion or early discontinuation |
Secondary
| Measure | Time frame |
|---|---|
| Objective response for patients with measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) | Through study completion or early discontinuation |
| Duration of objective response for patients with measurable disease according to RECIST | Through study completion or early discontinuation |
| Progression-free survival (PFS) for patients with measurable disease according to RECIST | Through study completion or early discontinuation |
Countries
United States
Outcome results
None listed