A Study Of Crizotinib Plus VEGF Inhibitor Combinations In Patients With Advanced Solid Tumors.

Sponsor
Pfizer
Study ID
NCT01441388
Phase
PHASE1
Status
Withdrawn

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Crizotinib plus VEGF inhibitor combinations — DRUG
    Three combinations will be prioritized, namely crizotinib plus axitinib, crizotinib plus sunitinib and crizotinib plus bevacizumab, with a fourth combination, crizotinib plus sorafenib to be tested only if crizotinib does not combine with either axitinib and/or sunitinib. All study drugs are tablets or capsules except for bevacizumab which is parenteral (intravenous). Dosage, frequency and duration to be determined.
  • Crizotinib plus axitinib — DRUG
    Study drugs are tablets or capsules; dosage, frequency and duration to be determined.
  • Crizotinib plus sunitinib — DRUG
    Study drugs are tablets or capsules; dosage, frequency and duration to be determined.
  • Crizotinib plus axitinib — DRUG
    Study drugs are tablets or capsules; dosage, frequency and duration to be determined.
  • Crizotinib plus sunitinib — DRUG
    Study drugs are tablets or capsules; dosage, frequency and duration to be determined.
  • Crizotinib plus bevacizumab — DRUG
    Study drugs are tablets or capsules except for bevacizumab which is parenteral (intravenous). Dosage, frequency and duration to be determined.
  • Crizotinib plus sorafenib — DRUG
    Study drugs are tablets or capsules; dosage, frequency and duration to be determined.

Study Details

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 and exhibit disease progression while on therapy. It is proposed that mesenchymal-epithelial transition factor (c-MET) and its ligand hepatocyte growth factor (HGF or scatter factor) contribute significantly 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 individual VEGF inhibitors. Three combinations will be prioritized, namely crizotinib plus axitinib, crizotinib plus sunitinib and crizotinib plus bevacizumab, with a fourth combination, crizotinib plus sorafenib to be tested only if crizotinib does not combine with either axitinib and/or sunitinib.

Key Dates

Start date
Dec 31, 2011
Status verified
Dec 2011
Primary completion
Nov 30, 2013
Completion
Nov 30, 2013

Study Design

Enrollment
0 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Dose Escalation
    Histological or cytological diagnosis of advanced/metastatic solid tumor that is resistant to standard therapy or for which no standard therapy is available.
  • Experimental: Expansion Population 1
    Patients with histologically confirmed metastatic renal cell cancer with no prior systemic therapy directed at the malignant tumor.
  • Experimental: 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.
  • Experimental: 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.
  • Experimental: 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.

Primary Outcome Measure

Dose Limiting Toxicities (DLTs). [ Time Frame: 12 months ]

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