Evaluating the Safety and Tolerability of GDC-0349 in Patients With Locally Advanced or Metastatic Solid Tumors or Non Hodgkin's Lymphoma

Genentech

Status and phase

Completed

Phase 1

Conditions

Non-Hodgkin's Lymphoma, Solid Tumor

Treatments

Drug: GDC-0349

Study type

Interventional

Funder types

Industry

Identifiers

NCT01356173

MKI4956g

MP00807 (Other Identifier)

Details and patient eligibility

About

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).

Enrollment

10 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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