A Phase 1b Study Of Axitinib In Combination With Crizotinib In Patients With Advanced Solid Tumors

Pfizer

Status and phase: Completed; Phase 1

Conditions: Advanced Solid Tumors

Treatments: Drug: axitinib; Drug: crizotinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT01999972

2015-001724-31 (EudraCT Number)

A4061068

Details and patient eligibility

About

Despite the success of anti-angiogenic therapy in multiple treatment settings, a fraction of patients are refractory to vascular endothelial growth factor (VEGF) inhibitor treatment, while the majority of patients will eventually develop evasive resistance. It is proposed that mesenchymal-epithelial transition factor (c-MET) and its ligand hepatocyte growth factor (HGF or scatter factor) contribute to VEGF inhibitor resistance, such that combining a c-MET inhibitor with a VEGF inhibitor will provide additional clinical activity compared to VEGF inhibitor alone. This hypothesis will be tested using the cMET/ALK inhibitor, crizotinib, in combination with the VEGF inhibitor, axitinib.Since this will be the first study of axitinib given in combination with crizotinib, the study will primarily assess the safety and tolerability of the combination regimen.

Enrollment: 50 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis - Dose Escalation Phase: Histologically or cytologically confirmed diagnosis of advanced solid tumor that is resistant to standard therapy or for which no standard therapy is available.
• Diagnosis - Dose Expansion Phase: Histologically or cytologically confirmed advanced RCC with a component of clear cell subtype
• Dose Expansion Phase: at least one measureable lesion as defined by RECIST [Response Evaluation Criterion in Solid Tumors] version 1.1.
• ECOG [Eastern Cooperative Oncology Group] Performance Status 0 or 1.

Exclusion criteria

• Major surgery <4 weeks or radiation therapy <2 weeks of patient registration.
• History of or known active seizure disorder, brain metastases, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease.
• Dose Expansion Phase only: diagnosis of any other malignancy within 2 years prior to registration.

Trial design

50 participants in 3 patient groups

Axitinib in combination with crizotinib, escalation phase

Experimental group

Description:

Dose Escalation Advanced solid tumor that is resistant to standard therapy or for which no standard therapy is available

Treatment:

Drug: axitinib

Drug: crizotinib

Drug: crizotinib

Drug: crizotinib

Drug: axitinib

Drug: axitinib

Expansion Phase Cohort 1

Experimental group

Description:

Dose Expansion, Cohort 1: axitinib in combination with crizotinib Advanced renal cell cancer \[RCC\] with no prior systemic therapy

Treatment:

Drug: axitinib

Drug: crizotinib

Drug: crizotinib

Drug: crizotinib

Drug: axitinib

Drug: axitinib

Expansion Phase Cohort 2

Experimental group

Description:

Dose Expansion, Cohort 2: axitinib in combination with crizotinib Advanced renal cell cancer with at least one but no more than two prior systemic treatment regimens directed at advanced RCC

Treatment:

Drug: axitinib

Drug: crizotinib

Drug: crizotinib

Drug: crizotinib

Drug: axitinib

Drug: axitinib