Safety, Tolerability and Pharmacokinetics of Cobimetinib in Combination With Pictilisib in Patients With Locally Advanced or Metastatic Solid Tumors
Condition: Solid Tumors
MeSH terms: Neoplasms
Intervention: Cobimetinib; Pictilisib
Intervention description: Repeated oral dosing.; Repeated oral dosing.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 178.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: GDC0941; GDC0973; MEK; MEK Inhibitor; PI3K; PI3K Inhibitor; PI3 Kinase; PI3 Kinase Inhibitor

Summary:

      This is an open-label, multicenter, Phase Ib dose-escalation study designed to assess the
      safety, tolerability and pharmacokinetics of oral dosing of cobimetinib and pictilisib
      administered in combination in patients with locally advanced or metastatic solid tumors.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically documented, locally advanced or metastatic solid
             tumors for which standard therapy either does not exist or has proven ineffective or
             intolerable

          -  Evaluable disease or disease measurable per Response Evaluation Criteria in Solid
             Tumors (RECIST)

          -  Life expectancy greater than or equal to (>=) 12 weeks

          -  Adequate hematologic and end organ function

          -  Agreement to use an effective form of contraception for the duration of the study

        Exclusion Criteria:

          -  History of prior significant toxicity from another mitogen-activated protein kinase
             (MEK) pathway inhibitor requiring discontinuation of treatment

          -  History of prior significant toxicity from another phosphoinositide 3-kinase (PI3K)
             pathway inhibitor requiring discontinuation of treatment

          -  Allergy or hypersensitivity to components of the cobimetinib or pictilisib
             formulations

          -  Palliative radiotherapy within 2 weeks prior to first dose of study drug treatment in
             Cycle 1

          -  Experimental therapy within 4 weeks prior to first dose of study drug treatment in
             Cycle 1

          -  Major surgical procedure or significant traumatic injury within 4 weeks prior to first
             dose of study drug treatment in Cycle 1, or anticipation of the need for major surgery
             during the course of study treatment

          -  Prior anti-cancer therapy within 28 days before the first dose of study drug treatment
             in Cycle 1

          -  History of diabetes requiring daily medication, or history of Grade >= 3 fasting
             hyperglycemia

          -  Current severe, uncontrolled systemic disease

          -  History of clinically significant cardiac or pulmonary dysfunction

          -  History of malabsorption or other condition that would interfere with enteral
             absorption

          -  Clinically significant history of liver disease (including cirrhosis), current alcohol
             abuse, or current known active infection with human immunodeficiency virus (HIV),
             hepatitis B virus, or hepatitis C virus

          -  Any condition requiring anticoagulants, such as warfarin, heparin, or thrombolytics

          -  Active autoimmune disease

          -  Uncontrolled ascites requiring weekly large volume paracentesis for 3 consecutive
             weeks prior to enrollment

          -  Pregnancy, lactation, or breastfeeding

          -  Known brain metastases that are untreated, symptomatic, or require therapy to control
             symptoms

          -  No other history of or ongoing malignancy that would potentially interfere with the
             interpretation of the pharmacodynamic or efficacy assays