Clinical trial NCT01875705: A Dose-Escalation Study of GDC-0994 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-0994 in Patients With Locally Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumor
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2013-06-12
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: OTHER

Brief summary: This is an open-label, multicenter, dose-escalation study to assess the safety, tolerability, and pharmacokinetics of GDC-0994 in patients with locally advanced or metastatic solid tumors. Patients will be enrolled in one of two stages: a dose-escalation stage (Stage I) or the subsequent expansion stage (Stage II). Stage I will evaluate the safety, tolerability, and pharmacokinetics of increasing doses of GDC-0994 administered daily. Stage II will gather additional data on safety, tolerability, and pharmacokinetics of the recommended dose of GDC-0994 determined in Stage I.


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 per RECIST 1.1
* Life expectancy \>= 12 weeks
* Adequate hematologic and end organ function
* Consent to provide archival tissue

Exclusion Criteria:

* History of prior significant toxicity from another MEK or ERK inhibitor requiring discontinuation of treatment
* History of parathyroid disorder or history or malignancy-associated hypercalcemia requiring therapy in the past 6 months
* Evidence of visible retinal pathology as assessed by ophthalmologic examination that is considered a risk factor for retinal vein thrombosis or neurosensory retinal detachment
* History of glaucoma
* Intraocular pressure \> 21 mmHg as measured by tonometry
* Predisposing factors to retinal vein occlusion, including uncontrolled hypertension, uncontrolled diabetes, uncontrolled hyperlipidemia, and coagulopathy
* History of retinal vein occlusion (RVO), neurosensory retinal detachment, or neovascular macular degeneration
* Allergy or hypersensitivity to components of the 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 first dose of study drug treatment in Cycle 1, or anticipation of the need for major surgery during the course of study treatment
* Prior anti-cancer therapy within 28 days or 5 times the half-life whichever is longer
* Current severe, uncontrolled systemic disease
* History of clinically significant cardiac dysfunction
* Pregnancy, lactation, or breastfeeding
* Active autoimmune disease
* Inability or unwillingness to swallow pills
* Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms
* Clinically significant history of liver disease (including cirrhosis), current alcohol abuse, or current known active infection with HIV, hepatitis B virus, or hepatitis C virus
* Any condition requiring warfarin or thrombolytic anticoagulants
* Uncontrolled ascites requiring weekly large volume paracentesis for 3 consecutive weeks prior to enrollment

Primary outcomes:
measure: Safety: Incidence of adverse events
timeFrame: Approximately 2 years
measure: Maximum tolerated dose
timeFrame: Approximately 2 years
measure: Dose-limiting toxicities
timeFrame: Approximately 2 years
measure: Pharmacokinetics: Area under the concentration-time curve
timeFrame: Approximately 2 years
measure: Pharmacokinetics: Maximum plasma concentrations
timeFrame: Approximately 2 years
measure: Pharmacokinetics: Minimum plasma concentrations
timeFrame: Approximately 2 years
measure: Pharmacokinetics: Time to maximum plasma concentration
timeFrame: Approximately 2 years
measure: Pharmacokinetics: Apparent terminal elimination half-life
timeFrame: Approximately 2 years
Secondary outcomes:
measure: To assess the PD effects of GDC-0994, as measured by changes in molecular biomarkers in pre- and post-treatment tumor tissues\n
timeFrame: Approximately 2 years
measure: Objective Response according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
timeFrame: Approximately 2 years
measure: Progression-free survival according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
timeFrame: Approximately 2 years
measure: Duration of response according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
timeFrame: Approximately 2 years
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale Cancer Center; Medical Oncology
state: Connecticut
city: Detroit
country: United States
facility: Karmanos Can Inst
state: Michigan
city: Nashville
country: United States
facility: Sarah Cannon Research Inst.
state: Tennessee
city: Villejuif
country: France
facility: Institut Gustave Roussy; Departement Oncologie Medicale
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
References: