Clinical trial NCT01676714: Study of Dovitinib and Biomarkers in Advanced Non-Small Cell Lung Cancer or Advanced Colorectal Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-Small Cell Lung Cancer
Colorectal Cancer
Keywords: Dovitinib
Fibroblast Growth Factor Receptor Biomarkers
Anti-Vascular Endothelial Growth Factor Therapy
Lead sponsor: University of California, Davis
Sponsor class: OTHER
Collaborators: name: Novartis
First posted: 2012-08-31
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Overall Response Rate
timeFrame: Up to 100 months
Secondary outcomes:
measure: Disease Control Rate
timeFrame: From start of treatment, up to 8 weeks
measure: Progression Free Survival
timeFrame: From start of treatment until the date of death from any cause, assessed up to 100 months
measure: Number of Patients Who Experienced Treatment Related Toxicities
timeFrame: Starting at screening and then at every visit and then up to 30 days after the last dose of study treatment.
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: University of California Comprehensive Cancer Center
state: California
Study officials:
affiliation: University of California, Davis
name: Thomas Semrad, MD
role: PRINCIPAL_INVESTIGATOR
References: