A Dose-Escalation Study of GDC-0994 in Patients With Locally Advanced or Metastatic Solid Tumors

Solid Tumor Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01875705
• Other study ID #: GO28885
• Secondary ID: 2013-000566-10
• Status: Completed
• Phase: Phase 1
• First received: June 10, 2013
• Last updated: April 5, 2018
• Start date: June 21, 2013
• Est. completion date: September 23, 2016

Study information

• Verified date: April 2018
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: September 23, 2016
• Est. primary completion date: September 23, 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 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

Related Conditions & MeSH terms

• Solid Tumor

Intervention

Drug:
• GDC-0994
Escalating doses of GDC-0994 until maximum tolerated dose is reached
• GDC-0994
Recommended dose determined in Stage I-Dose Escalation phase, until disease progression

Locations

Country	Name	City	State
France	Institut Gustave Roussy; Departement Oncologie Medicale	Villejuif
United States	Karmanos Can Inst	Detroit	Michigan
United States	Sarah Cannon Research Inst.	Nashville	Tennessee
United States	Yale Cancer Center; Medical Oncology	New Haven	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety: Incidence of adverse events		Approximately 2 years
Primary	Maximum tolerated dose		Approximately 2 years
Primary	Dose-limiting toxicities		Approximately 2 years
Primary	Pharmacokinetics: Area under the concentration-time curve		Approximately 2 years
Primary	Pharmacokinetics: Maximum plasma concentrations		Approximately 2 years
Primary	Pharmacokinetics: Minimum plasma concentrations		Approximately 2 years
Primary	Pharmacokinetics: Time to maximum plasma concentration		Approximately 2 years
Primary	Pharmacokinetics: Apparent terminal elimination half-life		Approximately 2 years
Secondary	To assess the PD effects of GDC-0994, as measured by changes in molecular biomarkers in pre- and post-treatment tumor tissues\n		Approximately 2 years
Secondary	Objective Response according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)		Approximately 2 years
Secondary	Progression-free survival according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)		Approximately 2 years
Secondary	Duration of response according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)		Approximately 2 years