A Study Evaluating the Safety, Tolerability, and Pharmacokinetics of GDC-0425 Administered With and Without Gemcitabine in Patients With Refractory Solid Tumors or Lymphoma
- 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
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 dose limiting toxicities (DLTs) Up to 35 days 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
- 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)
Sarah Cannon Cancer Center
🇺🇸Nashville, Tennessee, United States
Karmanos Cancer Institute..
🇺🇸Detroit, Michigan, United States
Institut Gustave Roussy; Ser. de Med. Nucleaire; Cancerologie Endo
🇫🇷Villejuif, France