A Phase 1b Study Of Axitinib In Combination With Crizotinib In Patients With Advanced Solid Tumors
Condition: Advanced Solid Tumors
MeSH terms: Neoplasms
Intervention: axitinib; crizotinib; axitinib; crizotinib; axitinib; crizotinib
Intervention description: Axitinib: tablets, dosage range 2 - 5 mg, given orally twice daily on a continuous dosing schedule in 28 days cycles.; Crizotinib: capsules, dosage range 200-250 mg, given orally twice daily or every day on a continuous dosing schedule in 28 days cycle.; Axitinib: tablets, dosage be defined based on Arm 1 results, given orally twice daily on a continuous dosing schedule in 28 days cycles.; Crizotinib: capsules, dosage be defined based on Arm 1 results, given orally twice daily or every day on a continuous dosing schedule in 28 days cycle.; Axitinib: tablets, dosage be defined based on Arm 1 results, given orally twice daily on a continuous dosing schedule in 28 days cycles.; Crizotinib: capsules, dosage be defined based on Arm 1 results, given orally twice daily or every day on a continuous dosing schedule in 28 days cycle.
Intervention MeSH terms: Axitinib; Crizotinib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Masking: None (Open Label)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Carcinoma; Renal Cell

Summary:

      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.
    

Eligibility criteria:

        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.