Solid Tumor
Conditions
Keywords
solid cancers
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.
Interventions
DRUGGDC-0425
Oral escalating dose
DRUGgemcitabine
Intravenous repeating dose
Sponsors
Genentech, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetic property of GDC-0425: determination of plasma drug concentration | Up to 12 months or early study discontinuation |
| Incidence 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 |
| Severity of all adverse events graded according to NCI CTCAE, v4.0 | Up to 1 year |
| 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 |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
Countries
France, United States
Outcome results
None listed