---
title: A Dose-Escalation Study of GDC-0994 in Patients With Locally Advanced or Metastatic Solid Tumors
nct_id: NCT01875705
overall_status: COMPLETED
phase: PHASE1
sponsor: Genentech, Inc.
study_type: INTERVENTIONAL
primary_condition: Solid Tumor
countries: United States, France
canonical_url: "https://parkinsonspathways.com/agent/trials/NCT01875705.md"
clinicaltrials_gov: "https://clinicaltrials.gov/study/NCT01875705"
ct_last_update_post_date: 2018-04-06
last_seen_at: "2026-05-12T06:21:48.285Z"
source: ClinicalTrials.gov (mirrored, no enrichment)
---
# 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

**NCT ID:** [NCT01875705](https://clinicaltrials.gov/study/NCT01875705)

## Key Facts

- **Status:** COMPLETED
- **Phase:** PHASE1
- **Study Type:** INTERVENTIONAL
- **Target Enrollment:** 40
- **Lead Sponsor:** Genentech, Inc.
- **Conditions:** Solid Tumor
- **Start Date:** 2013-06-21
- **Completion Date:** 2016-09-23
- **CT.gov Last Update:** 2018-04-06

## 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

- **Minimum age:** 18 Years
- **Sex:** ALL
- **Healthy Volunteers:** No

```
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
```

## Arms

- **Stage I-Dose Escalation** (EXPERIMENTAL)
- **Stage II-Cohort-Expansion** (EXPERIMENTAL)

## Interventions

- **GDC-0994** (DRUG) — Escalating doses of GDC-0994 until maximum tolerated dose is reached
- **GDC-0994** (DRUG) — Recommended dose determined in Stage I-Dose Escalation phase, until disease progression

## Primary Outcomes

- **Safety: Incidence of adverse events** _(time frame: Approximately 2 years)_
- **Maximum tolerated dose** _(time frame: Approximately 2 years)_
- **Dose-limiting toxicities** _(time frame: Approximately 2 years)_
- **Pharmacokinetics: Area under the concentration-time curve** _(time frame: Approximately 2 years)_
- **Pharmacokinetics: Maximum plasma concentrations** _(time frame: Approximately 2 years)_
- **Pharmacokinetics: Minimum plasma concentrations** _(time frame: Approximately 2 years)_
- **Pharmacokinetics: Time to maximum plasma concentration** _(time frame: Approximately 2 years)_
- **Pharmacokinetics: Apparent terminal elimination half-life** _(time frame: Approximately 2 years)_

## Secondary Outcomes

- **To assess the PD effects of GDC-0994, as measured by changes in molecular biomarkers in pre- and post-treatment tumor tissues\n** _(time frame: Approximately 2 years)_
- **Objective Response according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)** _(time frame: Approximately 2 years)_
- **Progression-free survival according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)** _(time frame: Approximately 2 years)_
- **Duration of response according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)** _(time frame: Approximately 2 years)_

## Locations (4)

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

## Recent Field Changes (last 30 days)

- `status.overallStatus` — added _(2026-05-12)_
- `status.primaryCompletionDate` — added _(2026-05-12)_
- `status.completionDate` — added _(2026-05-12)_
- `status.lastUpdatePostDate` — added _(2026-05-12)_
- `design.phases` — added _(2026-05-12)_
- `design.enrollmentCount` — added _(2026-05-12)_
- `eligibility.criteria` — added _(2026-05-12)_
- `eligibility.minAge` — added _(2026-05-12)_
- `eligibility.sex` — added _(2026-05-12)_
- `outcomes.primary` — added _(2026-05-12)_
- `outcomes.secondary` — added _(2026-05-12)_
- `armsInterventions.arms` — added _(2026-05-12)_
- `armsInterventions.interventions` — added _(2026-05-12)_
- `sponsor.lead` — added _(2026-05-12)_
- `results.hasResults` — added _(2026-05-12)_
- `locations.yale cancer center; medical oncology|new haven|connecticut|united states` — added _(2026-05-12)_
- `locations.karmanos can inst|detroit|michigan|united states` — added _(2026-05-12)_
- `locations.sarah cannon research inst.|nashville|tennessee|united states` — added _(2026-05-12)_
- `locations.institut gustave roussy; departement oncologie medicale|villejuif||france` — added _(2026-05-12)_

---

*Canonical: https://parkinsonspathways.com/agent/trials/NCT01875705.md*  
*Source data (authoritative): https://clinicaltrials.gov/study/NCT01875705*  
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