A Study Evaluating the Safety, Tolerability, and Pharmacokinetics of GDC-0425 Administered With and Without Gemcitabine in Patients With Refractory Solid Tumors or Lymphoma

Phase 1

Completed

• Conditions: Solid Tumor
• Interventions: Drug: GDC-0425; Drug: gemcitabine

• Registration Number: NCT01359696
• Lead Sponsor: Genentech, Inc.

Brief Summary

This is an open-label, multicenter, Phase I, dose-escalation study to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of GDC-0425 administered with and without gemcitabine.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-05-23
• Study First Submitted QC: 2011-05-24
• Study First Posted: 2011-05-25
• Study Start: 2011-07-11
• Primary Completion: 2014-05-29
• Study Completion: 2014-05-29
• Status Verified: 2017-04
• Last Update Submitted: 2017-04-11
• Last Update Posted: 2017-04-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1
• Signed Informed Consent Form
• Histologically or cytologically documented, locally advanced or metastatic solid tumors or lymphoma for which standard therapy either does not exist or has proven ineffective or intolerable
• Adequate hematologic and end-organ (liver and kidney) function
• For female patients of childbearing potential and male patients with partners of childbearing potential, agreement by the patient that the patient and/or partner will use an effective form of contraception
• Patients enrolled in certain phases must be willing to provide fresh and/or archival tumor samples

Exclusion Criteria

• History of prior significant toxicity from a same class of agents as GDC-0425 or gemcitabine requiring discontinuation of treatment
• Allergy, hypersensitivity or contraindication to the GDC-0425 formulation or gemcitabine
• Experimental therapy or anti-cancer therapy within 4 weeks prior to the first dose of study drug treatment
• Radiotherapy within 2 weeks prior to first dose of study drug treatment
• More than two regimens of cytotoxic chemotherapy for the treatment of locally advanced or metastatic cancer
• History of receiving high-dose chemotherapy requiring bone marrow or stem cell support
• History of receiving radiation to more than 25% of bone marrow-bearing areas
• Acute drug-related toxicities from previous therapies have not resolved prior to study entry, except for alopecia and mild neuropathy
• Current severe, uncontrolled systemic disease (including but not limited to clinically significant cardiovascular, pulmonary, or renal disease or ongoing or active infection) excluding cancer
• Significant heart disease and heart dysfunction including but not limited to uncontrolled severe hypertension, heart failure, and reduced cardiac contractility
• Uncontrolled ascites, due to diseases other than cancer
• Inability or unwillingness to swallow pills/capsules
• History of malabsorption or other condition that would interfere with drug absorption
• Any history of active stomach and/or intestine bleeding within the 6 months prior to screening
• Known HIV infection
• Pregnancy, lactation, or breastfeeding
• Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms
• Inability to comply with study and follow up procedures

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
A	gemcitabine	-
A	GDC-0425	-

Primary Outcome Measures

Name	Time	Method
Incidence of all adverse events graded according to NCI CTCAE, v4.0	Up to 1 year
Pharmacokinetic property of GDC-0425: determination of plasma drug concentration	Up to 12 months or early study discontinuation
Pharmacokinetic property of GDC-0425: exposure	Up to 12 months or early study discontinuation
Pharmacokinetic property of GDC-0425: half-life	Up to 12 months or early study discontinuation
Severity of all adverse events graded according to NCI CTCAE, v4.0	Up to 1 year
Incidence of dose limiting toxicities (DLTs)	Up to 35 days

Secondary Outcome Measures

Name	Time	Method
Antitumor activity of GDC-0425 in combination with gemcitabine: determination of tumor response using RECIST v1.1 for patients with measurable disease	Up to 12 months or early study discontinuation

Trial Locations

Locations (3)

Karmanos Cancer Institute..; 🇺🇸 Detroit, Michigan, United States

Sarah Cannon Cancer Center; 🇺🇸 Nashville, Tennessee, United States

Institut Gustave Roussy; Ser. de Med. Nucleaire; Cancerologie Endo; 🇫🇷 Villejuif, France