A Phase 1B, Open-Label, Dose Escalation Study To Evaluate Safety, Pharmacokinetics And Pharmacodynamics Of Crizotinib (PF-02341066) Plus VEGF Inhibitor Combinations In Patients With Advanced Solid Tumors.
- Dose Escalation Population: Histological or cytological diagnosis of
advanced/metastatic solid tumor that is resistant to standard therapy or for which no
standard therapy is available. Lesions may be measurable or non measurable.
- Expansion Population 1: Patients with histologically confirmed metastatic renal cell
cancer with no prior systemic therapy directed at the malignant tumor.
- Expansion Population 2: Patients with histologically confirmed metastatic renal cell
cancer whose prior systemic therapy directed at the malignant tumor was single agent
VEGF inhibitor and who now have acquired resistance to this treatment. Resistance is
defined as progression following an initial response (complete or partial), or stable
disease for at least 6 months on single agent VEGF inhibitor.
- Expansion Population 3: Patients with histologically confirmed glioblastoma whose
disease has failed on previous therapy, and which must have included treatment with
external beam radiation and temozolomide chemotherapy, and who now have
radiographically recurrent or progressive disease.
- Expansion Population 4: Patients with histologically confirmed advanced-stage
(unresectable or metastatic) hepatocellular carcinoma who have not received previous
systemic therapy directed at the malignant tumor will be eligible to receive
crizotinib plus sorafenib, should this combination be tested. Eligibility criteria
also include normal hepatic function or Child-Pugh hepatic function class A.
- Patients with hemorrhagic brain metastases or with known symptomatic brain metastases
- Major surgery within 4 weeks of starting study treatment.
- Radiation therapy within 2 weeks of starting study treatment.
- Hypertension that cannot be controlled with medications (>150/90 mmHg despite optimal
- For glioblastoma patients: Prior treatment of glioblastoma with Gliadel wafers,
stereotactic radiation, or brachytherapy unless there is pathological or definitive
radiological evidence (PET scan or perfusion MRI) of recurrent tumor or unless there
is new enhancement outside of the radiation field. History of Grade 2 or greater
acute intracranial hemorrhage. Radiation therapy (RT) for glioblastoma within 3
months unless there is either: a) histopathologic confirmation of recurrent tumor, or
b) new enhancement on MRI outside of the RT treatment field.Concomitant treatment
with therapeutic doses of anticoagulants (low dose warfarin (Coumadin) up to 2 mg PO
daily for deep vein thrombosis prophylaxis is allowed).