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

Glioblastoma Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01441388
• Other study ID #: A8081030
• Status: Withdrawn
• Phase: Phase 1
• First received: September 23, 2011
• Last updated: December 19, 2011
• Start date: December 2011
• Est. completion date: November 2013

Study information

• Verified date: December 2011
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: November 2013
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• Patients with hemorrhagic brain metastases or with known symptomatic brain metastases requiring steroids.

• 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 medical therapy).

• 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).

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Carcinoma, Renal Cell
• Glioblastoma

Intervention

Drug:
• Crizotinib plus VEGF inhibitor combinations
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
Study drugs are tablets or capsules; dosage, frequency and duration to be determined.
• Crizotinib plus sunitinib
Study drugs are tablets or capsules; dosage, frequency and duration to be determined.
• Crizotinib plus axitinib
Study drugs are tablets or capsules; dosage, frequency and duration to be determined.
• Crizotinib plus sunitinib
Study drugs are tablets or capsules; dosage, frequency and duration to be determined.
• Crizotinib plus bevacizumab
Study drugs are tablets or capsules except for bevacizumab which is parenteral (intravenous). Dosage, frequency and duration to be determined.
• Crizotinib plus sorafenib
Study drugs are tablets or capsules; dosage, frequency and duration to be determined.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Limiting Toxicities (DLTs).		12 months	Yes
Secondary	Duration of Response (DR)		24 months	No
Secondary	Progression free survival (PFS)		24 months	No
Secondary	Area under the plasma concentration versus time curve (AUC) of crizotinib and each VEGF inhibitor		24 months	No
Secondary	Best overall response, as assessed using the Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1 or , in the case of GBM (glioblastoma multiforme , RANO (Response Assessment in Neuro-Oncology) criteria.		24 months	No
Secondary	Overall survival (OS) up to 12 months		24 months	No
Secondary	Pre- and post-dose levels of soluble peripheral blood biomarkers.		24 months	No
Secondary	Tumor tissue biomarkers.		18 months	No
Secondary	6-month progression free survival proportion (PFS6) for glioblastoma patients		24 months	No
Secondary	Peak plasma concentration (Cmax) of crizotinib and each VEGF inhibitor		24 months	No

External Links

•   To obtain contact information for a study center near you, click here.