A Study of GDC-0941 in Patients With Locally Advanced or Metastatic Solid Tumors or Non-Hodgkin's Lymphoma for Which Standard Therapy Either Does Not Exist or Has Proven Ineffective or Intolerable

Genentech

Status and phase

Completed

Phase 1

Conditions

Non-Hodgkin's Lymphoma, Solid Cancers

Treatments

Drug: GDC-0941

Study type

Interventional

Funder types

Industry

Identifiers

NCT00876122

GO01299 (Other Identifier)

GDC4254g

Details and patient eligibility

About

This is an open-label, Phase I, dose-escalation study using a 3 + 3 design to assess the safety, tolerability, and pharmacokinetics of orally administered GDC-0941 administered QD. This study will include patients with locally advanced or metastatic solid tumors, NHL, or multiple myeloma (MM) (expansion stage only) for which standard therapy either does not exist or has proven ineffective or intolerable.

Enrollment

60 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Histologically or cytologically documented, incurable, locally advanced or metastatic solid malignancy or NHL without leukemic phase that has progressed or has failed to respond to at least one prior regimen
Multiple myeloma (MM) patients (only in Stage 2): documented pathologic diagnosis of MM that has relapsed or that has failed to respond after treatment with at least one prior systemic therapy (other than corticosteroid monotherapy)
Evaluable or measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) or per International Working Group (IWG) response criteria for Non-Hodgkin's lymphoma (NHL) patients
Life expectancy of >= 12 weeks
Documented willingness to use an effective means of contraception for both men and women while participating in the study
For patients participating in Stage 1 after an adequate exposure has been predicted or observed on the basis of PK analysis and for approximately 12 patients participating in Stage 2 (excluding patients with MM): A biopsy-accessible lesion from which tissue can be obtained safely with CT guidance or direct visualization and agreement from the patient to undergo sequential (pre-treatment and post-treatment) biopsies.
For patients participating in Stage 2 DCE-MRI and MRS imaging: Patients will have at least one metastatic liver lesion measuring >= 5 cm in one dimension or one tumor lesion elsewhere measuring >= 2 cm in one dimension (lung and mediastinum lesions do not qualify) on the basis of CT scans

Exclusion criteria

Leptomeningeal disease as the only manifestation of the current malignancy
History of Type 1 or 2 diabetes mellitus requiring regular medication
Any condition requiring anti-coagulants, such as warfarin, heparin, or thrombolytics
Inability or unwillingness to swallow pills
Malabsorption syndrome or other condition that would interfere with enteral absorption
Known untreated CNS malignancies or treated brain metastases that are not radiographically stable for >= 3 months
Congenital long QT syndrome or QTc > 500 msec, as determined by at least two of the three baseline ECG measurements
Active congestive heart failure or ventricular arrhythmia requiring medication
Uncontrolled ascites requiring weekly large volume paracentesis for 3 consecutive weeks prior to enrollment
Active infection requiring intravenous (IV) antibiotics
Patients requiring any daily supplemental oxygen
DLco, 50% predicted value corrected for AV and Hgb prior to initiation of study treatment
Uncontrolled hypomagnesemia or hypokalemia, defined as values below the lower limit of normal (LLN) or hypercalcemia above the ULN for the institution despite adequate electrolyte supplementation or management
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 or that may affect the interpretation of the results or renders the patients at high risk from treatment complications
Significant traumatic injury within 3 weeks before Day 1
Major surgical procedure within 4 weeks prior to initiation of study treatment
Prior allogeneic hematopoietic stem cell transplantation (HSCT) at any time or autologous HSCT within 12 weeks of study entry
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 (exceptions are kinase inhibitors that are approved by the local regulatory authorities, which may be used within 2 weeks prior to initiation of study treatment, provided that any drug-related toxicity has completely resolved and after approval by the Medical Monitor has been granted)
Palliative radiation to bony metastases within 2 weeks prior to initiation of study treatment
Need for chronic corticosteroid therapy
Treatment with an investigational agent within 4 weeks prior to initiation of study treatment
Unresolved toxicity from prior therapy, except for alopecia and Grade 1 peripheral neuropathy
Pregnancy or lactation
Inability to comply with study and follow-up procedures
For patients eligible to participate in Stage 2 DCE-MRI and MRS assessments, any contraindication to MRI examination, including the following: