Study of Dovitinib and Biomarkers in Advanced Non-Small Cell Lung Cancer or Advanced Colorectal Cancer

Study Overview
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Brief Summary
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The purpose of this study is to find out if dovitinib is an effective treatment for patients with advanced lung cancer or advanced colorectal cancer (CRC) who have progressed on anti-vascular endothelial growth factor (VEGF) treatment.

Detailed Description
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The purposes of this study are 1) to evaluate the clinical efficacy of dovitinib and 2) to prospectively estimate the prevalence of fibroblast growth factor (FGF) signaling alterations in patients with advanced non-squamous non small cell lung cancer (NSCLC) or advanced CRC who have progressed on anti-VEGF treatment. Additionally, the investigators will make exploratory initial observations of the relationship between FGF signaling alterations and the clinical activity of dovitinib. This trial is expected to provide key biologic information that will inform the clinical development of dovitinib and provide initial evaluation of the analytic characteristics of these potential predictive biomarkers of its efficacy.

Official Title
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Phase II Study of Dovitinib and Pilot Study of Fibroblast Growth Factor Receptor Biomarkers in Advanced Non-Small Cell Lung Cancer or Advanced Colorectal Cancer Previously Treated With Anti-Vascular Endothelial Growth Factor Therapy

Conditions
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Non-Small Cell Lung Cancer, Colorectal Cancer

Intervention / Treatment
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* Drug: Dovitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed non-small cell lung cancer or colorectal cancer for which no potentially curative treatment options are available Any number of prior treatment regimens are allowed Immediate prior treatment regimen must have included an anti-VEGF agent. Acceptable anti-VEGF therapy includes bevacizumab, sunitinib, or sorafenib. For other anti-VEGF therapies, contact the principal investigator. Last dose administered of bevacizumab must be at least 21-days but not more than 56-days from enrollment. Last dose of anti-VEGF tyrosine kinase inhibitor must be at least 7-days but not more than 56-days from enrollment. Willingness to consent to research biopsy Measurable disease by RECIST 1.1 criteria Available tumor site amenable to core needle biopsy as determined by the treating investigator. Any questions regarding suitability of site for biopsy will be adjudicated by the principal investigator. Zubrod (ECOG) performance status 0 or 1 Age ≥ 18 years old Patients who give a written informed consent Patients must have the following laboratory values: Platelets ≥ 100 x 109/L Absolute neutrophil count ≥ 1.5 x 109/L Hemoglobin > 9 g/dL Serum total bilirubin: ≤ 1.5 x upper limit of normal ULN ALT and AST ≤ 3.0 x ULN ( with or without liver metastases) Serum creatinine ≤ 1.5 x ULN or serum creatinine >1.5 - 3 x ULN Exclusion Criteria: Patients with known brain metastases Patients with another primary malignancy within 3 years prior to starting study drug, with the exception of adequately treated in-situ carcinoma of the uterine cervix, or skin cancer Patients who have received the last administration of an anticancer therapy including chemotherapy, immunotherapy, hormonal therapy and monoclonal antibodies that have not resolved to NCI CTCAE grade 1 or less. Patients who have received the last administration of nitrosurea or mitomycin-C ≤ 6 weeks prior to starting study drug, or who have side effects that have not resolved to NCI CTCAE grade 1 or less. Patients who have received targeted therapy ≤ 1 week prior to starting study drug, or who have not recovered from the side effects of such therapy Patients who have had radiotherapy ≤ 4 weeks prior to starting study drug, or ≤ 2 weeks prior to starting study drug in the case of localized radiotherapy or who have not recovered from radiotherapy toxicities Patients who have undergone major surgery, open biopsy or significant traumatic injury ≤ 4 weeks prior to starting study drug, or patients who have had minor procedures, percutaneous biopsies or placement of vascular access device ≤ 1 week prior to starting study drug, or who have not recovered from side effects of such procedure or injury Patients with any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study: Impaired cardiac function or clinically significant cardiac diseases Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of dovitinib Cirrhosis, chronic active hepatitis or chronic persistent hepatitis Known diagnosis of human immunodeficiency virus infection Patients who are currently receiving anticoagulation treatment with therapeutic doses of warfarin Other concurrent severe and/or uncontrolled concomitant medical conditions Pregnant or breast-feeding women Women of child-bearing potential, who are biologically able to conceive, not employing two forms of highly effective contraception. Fertile males not willing to use contraception, as stated above Patients unwilling or unable to comply with the protocol

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dovitinib<br>500 mg of dovitinib (5 capsules) once a day for 5 continuous days and stop for 2 days. Continue to take dovitinib capsules in this manner until until progression or unacceptable toxicity develops. | Drug: Dovitinib<br> <br> * Other names: TK1258;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | Up to 100 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate | The total number of patients who demonstrate a response to treatment. Measured by RECIST 1.1 criteria. | From start of treatment, up to 8 weeks | 
| Progression Free Survival | The length of time during and after the treatment of the cancer that a patient lives with the disease but it does not get worse. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. | From start of treatment until the date of death from any cause, assessed up to 100 months | 
| Number of Patients Who Experienced Treatment Related Toxicities | Toxicities will be summarized by the type, severity (by NCI CTCAE), time of onset, duration, and outcome. Toxicity will be graded according to the NCI CTCAE version 4.0. | Starting at screening and then at every visit and then up to 30 days after the last dose of study treatment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dovitinib, Fibroblast Growth Factor Receptor Biomarkers, Anti-Vascular Endothelial Growth Factor Therapy