Clinical trial NCT01106599: A Study Evaluating the Safety, Tolerability, and Pharmacokinetics of GDC-0623 in Patients With Locally Advanced or Metastatic Solid Tumors
Official title: An Open-label, Phase I, Dose Escalation Study Evaluating the Safety, Tolerability and Pharmacokinetics of GDC-0623 Administered Daily in Patients With Locally Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Cancers
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2010-04-20
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Incidence and nature of dose-limiting toxicities (DLTs)
timeFrame: Through study completion or early discontinuation
measure: Incidence, nature, and severity of adverse events and serious adverse events, graded according to NCI CTCAE, v4.0
timeFrame: Through study completion or early discontinuation
measure: Pharmacokinetic parameters of GDC-0623 (total exposure, maximum and minimum plasma concentrations, time to maximum plasma concentration, elimination half-life)
timeFrame: Through study completion or early discontinuation
Secondary outcomes:
measure: Objective response for patients with measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST)
timeFrame: Through study completion or early discontinuation
measure: Duration of objective response for patients with measurable disease according to RECIST
timeFrame: Through study completion or early discontinuation
measure: Progression-free survival (PFS) for patients with measurable disease according to RECIST
timeFrame: Through study completion or early discontinuation
Other outcomes:
Locations:
city: Los Angeles
country: United States
state: California
city: Sacramento
country: United States
state: California
city: Oklahoma City
country: United States
state: Oklahoma
city: Nashville
country: United States
state: Tennessee
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
References: