- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01441388
A Study Of Crizotinib Plus VEGF Inhibitor Combinations In Patients With Advanced Solid Tumors.
December 19, 2011 updated by: Pfizer
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.
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.
Study Overview
Status
Withdrawn
Study Type
Interventional
Phase
- Phase 1
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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 Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
|
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.
|
EXPERIMENTAL: Expansion Population 1
Patients with histologically confirmed metastatic renal cell cancer with no prior systemic therapy directed at the malignant tumor.
|
Study drugs are tablets or capsules; dosage, frequency and duration to be determined.
Study drugs are tablets or capsules; dosage, frequency and duration to be determined.
|
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.
|
Study drugs are tablets or capsules; dosage, frequency and duration to be determined.
Study drugs are tablets or capsules; dosage, frequency and duration to be determined.
|
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.
|
Study drugs are tablets or capsules except for bevacizumab which is parenteral (intravenous).
Dosage, frequency and duration to be determined.
|
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.
|
Study drugs are tablets or capsules; dosage, frequency and duration to be determined.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Dose Limiting Toxicities (DLTs).
Time Frame: 12 months
|
12 months
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Progression free survival (PFS)
Time Frame: 24 months
|
24 months
|
Duration of Response (DR)
Time Frame: 24 months
|
24 months
|
Area under the plasma concentration versus time curve (AUC) of crizotinib and each VEGF inhibitor
Time Frame: 24 months
|
24 months
|
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.
Time Frame: 24 months
|
24 months
|
Overall survival (OS) up to 12 months
Time Frame: 24 months
|
24 months
|
Pre- and post-dose levels of soluble peripheral blood biomarkers.
Time Frame: 24 months
|
24 months
|
Tumor tissue biomarkers.
Time Frame: 18 months
|
18 months
|
6-month progression free survival proportion (PFS6) for glioblastoma patients
Time Frame: 24 months
|
24 months
|
Peak plasma concentration (Cmax) of crizotinib and each VEGF inhibitor
Time Frame: 24 months
|
24 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
December 1, 2011
Primary Completion (ANTICIPATED)
November 1, 2013
Study Completion (ANTICIPATED)
November 1, 2013
Study Registration Dates
First Submitted
September 23, 2011
First Submitted That Met QC Criteria
September 26, 2011
First Posted (ESTIMATE)
September 27, 2011
Study Record Updates
Last Update Posted (ESTIMATE)
December 20, 2011
Last Update Submitted That Met QC Criteria
December 19, 2011
Last Verified
December 1, 2011
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Urologic Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Kidney Diseases
- Urologic Diseases
- Adenocarcinoma
- Neoplasms, Glandular and Epithelial
- Digestive System Neoplasms
- Liver Diseases
- Astrocytoma
- Glioma
- Neoplasms, Neuroepithelial
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Kidney Neoplasms
- Liver Neoplasms
- Carcinoma, Renal Cell
- Carcinoma
- Glioblastoma
- Carcinoma, Hepatocellular
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Protein Kinase Inhibitors
- Sorafenib
- Sunitinib
- Bevacizumab
- Axitinib
- Crizotinib
Other Study ID Numbers
- A8081030
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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