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

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

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.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer; Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Dovitinib

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95817
      • University of California Comprehensive Cancer Center

Participation Criteria

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:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dovitinib; 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; Other Names: TK1258

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: University of California, Davis
• Collaborators: Novartis
• Investigators: Principal Investigator: Thomas Semrad, MD, University of California, Davis

Study record dates

Study Major Dates

• Study Start: February 1, 2013
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: August 27, 2012
• First Submitted That Met QC Criteria: August 30, 2012
• First Posted (Estimate): August 31, 2012

Study Record Updates

• Last Update Posted (Actual): January 10, 2018
• Last Update Submitted That Met QC Criteria: January 5, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: Dovitinib; Fibroblast Growth Factor Receptor Biomarkers; Anti-Vascular Endothelial Growth Factor Therapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms
• Other Study ID Numbers: UCDCC#231; 344991 (Other Grant/Funding Number: UC Davis); CTKI258AUS21T (Other Grant/Funding Number: Novartis)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No