A Study Evaluating the Safety, Tolerability, and Pharmacokinetics of GDC-0425 Administered With and Without Gemcitabine in Patients With Refractory Solid Tumors or Lymphoma

Study Overview
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Brief Summary
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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.

Official Title
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An Open-Label, Phase I, Dose Escalation Study Evaluating the Safety, Tolerability, and Pharmacokinetics of GDC-0425 Administered With and Without Gemcitabine in Patients With Refractory Solid Tumors or Lymphoma

Conditions
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Solid Tumor

Intervention / Treatment
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* Drug: GDC-0425
* Drug: gemcitabine


Participation Criteria
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Eligibility Criteria
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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

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-0425<br>* Oral escalating dose<br>Drug: gemcitabine<br>* Intravenous repeating dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Pharmacokinetic property of GDC-0425: determination of plasma drug concentration |  | Up to 12 months or early study discontinuation | 
| 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 | 
| Severity of all adverse events graded according to NCI CTCAE, v4.0 |  | Up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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solid cancers