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

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

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.

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