Non-Hodgkin's Lymphoma, Solid Tumor
Conditions
Keywords
solid cancers
Brief summary
This is an open-label, multicenter, Phase I, dose-escalation study to assess the safety, tolerability, and pharmacokinetic (PK) of GDC-0349 administered once daily (QD), orally (PO).
Interventions
DRUGGDC-0349
Oral escalating dose
Sponsors
Genentech, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically documented, locally advanced or metastatic solid malignancy or NHL without leukemic phase that has progressed or failed to respond to at least one prior regimen and/or are not candidates for regimens known to provide clinical benefit * Evaluable or measurable disease per RECIST v1.1 or IWG response criteria for patients with NHL and/or the following: prostate cancer patients with non-measurable disease are eligible if they have two rising prostate-specific antigen (PSA) levels \>= 5 ng/mL measured \>= 2 weeks apart that meet the PSA, and Working Group criteria for progression prior to initiation of study treatment, and ovarian cancer patients with non-measurable disease are eligible if they have two rising CA-125 levels greater than the ULN \>= 2 weeks apart prior to initiation of study treatment. * ECOG performance status of 0 or 1 at screening * Life expectancy of \>= 12 weeks * Adequate hematologic and organ function within 14 days prior to initiation of study treatment * Documented willingness to use an effective means of contraception for both men and women while participating in the study and for 90 days after the last dose of GDC-0349 * Willingness to provide archival tumor tissue
Exclusion criteria
* Leptomeningeal disease as the only manifestation of the current malignancy * History of Type 1 or 2 diabetes requiring daily medication * Known untreated central nervous system (CNS) malignancies or treated brain metastases that are not radiographically stable for \>= 3 months prior to initiation of study treatment * Active congestive heart failure or ventricular arrhythmia requiring medication * Uncontrolled ascites requiring weekly large-volume paracentesis for 3 consecutive weeks prior to initiation of study treatment * Active infection requiring intravenous (IV) antibiotics * Patients requiring any daily supplemental oxygen * Uncontrolled hypomagnesemia or hypokalemia * Any condition requiring anti-coagulants such as warfarin, heparin, or anti-thrombotics. Prophylactic anti-coagulation and/or local application of thrombolytic agents for catheter patency may be allowed for patients with normal INR and with prior approval from the Medical Monitor * Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis * Known human immunodeficiency virus (HIV) infection * Any other diseases, active or uncontrolled pulmonary dysfunction, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, that may affect the interpretation of the results, or renders the patients at high risk from treatment complications * Significant traumatic injury within 3 weeks prior to initiation of GDC-0349 * Major surgical procedure within 4 weeks prior to initiation of GDC-0349 * Treatment with chemotherapy, hormonal therapy (except GnRH agonists or antagonists for prostate cancer), immunotherapy, biologic therapy, or radiation therapy (except palliative radiation to bony metastases) as cancer therapy within 4 weeks prior to initiation of study treatment. Kinase inhibitors, approved by national regulatory authorities, may be used up to 2 weeks prior to initiation of GDC-0349, provided that any drug-related toxicity has completely resolved and prior approval is obtained from the Medical Monitor. * Palliative radiation to bony metastases within 2 weeks prior to initiation of GDC-0349 * Treatment with an investigational agent within 4 weeks prior to initiation of GDC-0349 * Unresolved toxicity from prior therapy, except for alopecia and Grade 1 peripheral neuropathy * Pregnancy or lactation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of dose limiting toxicities (DLTs) by NCI CTCAE v4.0 grade and associated dose of GDC-0349 | Up to 30 days |
Secondary
| Measure | Time frame |
|---|---|
| Incidence of adverse events by NCI CTCAE v4.0 grade and associated dose of GDC-0349 | Up to 2 years |
| Incidence of Grade 3 and 4 abnormalities in safety related laboratory parameters and associated dose of GDC-0349 | Up to 30 days |
Countries
Canada, United States
Outcome results
None listed