A Study of the Safety and Pharmacokinetics of GDC-0152, Administered Intravenously to Patients With Locally Advanced or Metastatic Malignancies

Study Overview
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Brief Summary
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The study consists of two stages. In Stage 1, maximum tolerated dose (MTD) will be determined. In Stage 2, additional patients will be treated at the MTD of GDC-0152.

Official Title
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A Phase Ia, Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of GDC-0152, an IAP Protein Antagonist, Administered Intravenously to Patients With Locally Advanced or Metastatic Malignancies

Conditions
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Solid Cancers

Intervention / Treatment
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* Drug: GDC-0152


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Histologically documented, incurable, locally advanced or metastatic solid malignancies, or non-Hodgkin's lymphoma (NHL) without leukemic phase Disease (either target or non-target lesions) that can be assessed by imaging studies and/or physical examination For patients with solid tumors or NHL without leukemic phase, disease progression on or after standard therapy, or a malignancy for which there is no standard therapy All prior therapy-related toxicities have recovered to baseline-grade toxicity with the exception of alopecia. Life expectancy of ≥ 60 days Resting oxygen saturation ≥ 92% on room air Agreement to use an effective form of contraception for the duration of the study Exclusion Criteria History of central nervous system disease Chemotherapy, cancer hormonal therapy (except GnRH agonists), radiotherapy, or immunotherapy within 4 weeks prior to Day 1 (6 weeks for nitrosoureas or mitomycin) Use of any other investigational agent or device Major surgery or significant traumatic injury within 3 weeks prior to Day 1 Pregnant or nursing Clinically significant cardiovascular disease, New York Heart Association (NYHA) Classification Grade 2 or greater congestive heart failure, a ventricular arrhythmia requiring medication within 1 year prior to Day 1, or NYHA Grade 2 or greater peripheral vascular disease on Day 1 Known HIV infection Patients with ongoing inflammatory processes or a Grade ≥ 2 fever or Grade ≥ 2 fever-associated constitutional symptoms (including rigors/chills, sweating, and others determined by the investigator), or a clinically significant systemic infection within the last month Any other diseases, 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 patient at high risk from treatment complications History of any chronic liver disease, active hepatic infection, or evidence of hepatic cirrhosis, or Grade ≥ 2 liver dysfunction. Baseline oxygen requirement or history of pulmonary fibrosis Any signs or symptoms Grade ≥ 2 by National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0, at study entry except for alopecia, pain, asymptomatic Grade 2 diffusing capacity of the lung for carbon monoxide (at the discretion of the investigator) or where otherwise specified Patients who need to take a concomitant medication, dietary supplement, or food that is a known inhibitor/inducer of the CYP3A4/5 and/or the 2C8 metabolic pathway or that has a narrow therapeutic window and involves these enzymes for their metabolism

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Drug: GDC-0152<br>* Intravenous escalating dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and nature of dose-limiting toxicities |  | Through study completion or early study discontinuation | 
| Incidence, nature, and severity of adverse events |  | Through study completion or early study discontinuation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameters of GDC-0152 (total plasma exposure, maximum plasma concentration, and total plasma clearance) |  | Through study completion or early study discontinuation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GDC0152, IAP, IAP Antagonist