Dovitinib for Patients With Tumor Pathway Activations Inhibited by Dovitinib
SIGNATURE
Modular Phase II Study to Link Targeted Therapy to Patients With Pathway Activated Tumors: Module 2 - Dovitinib for Patients With Tumor Pathway Activations Inhibited by Dovitinib Including Tumors With Mutations or Translocations of FGFR, PDGFR, VEGF, cKIT, FLT3, CSFR1, Trk and RET
1 other identifier
interventional
80
1 country
49
Brief Summary
The purpose of this signal seeking study was to determine whether treatment with dovitinib (TKI258) demonstrated sufficient efficacy in select pathway-activated solid tumors and/or hematologic malignancies to warrant further study.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Aug 2013
49 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 11, 2013
CompletedFirst Posted
Study publicly available on registry
April 15, 2013
CompletedStudy Start
First participant enrolled
August 1, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2015
CompletedResults Posted
Study results publicly available
March 20, 2017
CompletedMarch 20, 2017
January 1, 2017
2.3 years
April 11, 2013
January 30, 2017
January 30, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Clinical Benefit Rate (CBR)
CBR determined by investigator assessment for each tumor assessment \& defined as responses of Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) ≥ 16 wks. Confirmed CR/PR or SD prior to 16 wks,but discontinued prior to 16 wks for reasons other than progressive disease,will have their clinical benefit defined non-evaluable; confirmed CR/PR or SD prior to 16 wks,but progressed prior to 16 wks,will be considered not achieving clinical benefit;if CR/PR/SD occurred prior to 16 wks,but progressed at or after 16 wks without evidence of CR/PR/SD at or after 16 wks,will also be considered not achieving clinical benefit. CBR will be analyzed by comparing achieved CBR with a historical control rate of each tumor type,\& if there is at least 90% probability that the response rate in a tumor type exceeds the historical rate,then the tumor type will be considered a success. CBR: CR+PR+SD the assessment criteria was RECIST 1.1
Week 16
Secondary Outcomes (3)
Overall Response (OR) of Partial Response (PR) or Greater
Week 16
Progression-Free Survival (PFS)
36 months
Overall Survival (OS)
36 months
Study Arms (1)
TKI258
EXPERIMENTALDovitinib (TKI) will be dosed on a flat scale of 500 mg on a 5 days on/2 days off dosing schedule.
Interventions
Dovitinib (TKI) will be dosed on a flat scale of 500 mg on a 5 days on/2 days off dosing schedule.
Eligibility Criteria
You may qualify if:
- Patient's age was ≥ 18 years of age at the time of signing informed consent.
- Patient had a confirmed diagnosis of a selected solid tumor (except for primary diagnosis of urothelial tumors, hepatocellular carcinoma (HCC), endometrial carcinoma, metastatic breast cancer (mBC), squamous NSCLC, and renal cell carcinoma (RCC)) or hematologic malignancies (except for primary diagnosis of FLT3 AML and multiple myeloma). Additional tumor types could be excluded during the course of the study in the case of early futility or success based upon an interim analysis or at the discretion of Novartis.
- Patient was in need of treatment because of progression or relapse defined as:
- radiological progression for solid tumor and lymphoma
- for hematologic malignancies, measureable progression or relapse by appropriate criteria
- Patients had pre-identified tumor with a mutation and/or translocation of one of the known kinase targets of dovitinib. The qualifying alteration were assessed and reported by a CLIA-certified laboratory. The mutations included:
- FGFR 1-3 (amplifications were also allowed)
- PDGFRα or PDGFRβ
- VEGFR1-2 (KDR)
- FLT3, cKIT (amplifications are also allowed),
- RET, TrkA (NTRK1), or CSF-1R
- Patient had archival tissue available for submission to allow for molecular testing related to pathway activation. If the tissue was not available or not of sufficient quantity the patient was willing to undergo a fresh tumor biopsy to allow for this analysis. The sample was submitted prior to first study dose unless agreed upon between Novartis and the investigator.
- Patient received at least one prior treatment for recurrent, metastatic and /or locally advanced disease and for whom no standard therapy options were anticipated to result in a durable remission.
- Diffuse large B cell lymphoma only: Patient received or was ineligible for autologous or allogeneic stem cell transplant. This did not apply to patients with Mantle cell lymphoma or follicular lymphoma
- Patients with measurable disease as per appropriate guidelines:
- +22 more criteria
You may not qualify if:
- Patients eligible for this study did not meet any of the following criteria:
- Patients who received prior treatment with dovitinib (TKI258).
- Patients with a known hypersensitivity to dovitinib (TKI258) or to its excipients.
- Patients with brain metastasis or history of brain metastasis or leptomeningeal carcinomatosis.
- Patients with diarrhea ≥ CTCAE grade 2.
- Patients with neuropathy ≥ CTCAE grade 2.
- Patients with acute or chronic pancreatitis.
- Patients with external biliary drains.
- Patients with a history of pulmonary embolism (PE), or untreated deep venous thrombosis (DVT) ≤ 6 months prior to starting study drug. Note: Patients with recent DVT who were treated with therapeutic anti-coagulant agents for at least 6 weeks are eligible.
- Patients with impaired cardiac function or clinically significant cardiac diseases, including any of the following:
- History or presence of serious uncontrolled ventricular arrhythmias.
- Clinically significant resting bradycardia.
- LVEF assessed by either 2-D echocardiogram (ECHO) \< 50% or lower limit of normal (whichever was the higher), or 2-D multiple gated acquisition scan (MUGA) \< 45% or lower limit of normal (whichever was the higher).
- Any of the following within 6 months prior to starting study drug: myocardial infarction (MI), severe/unstable angina, coronary artery bypass graft (CABG), congestive heart failure (CHF), cerebrovascular accident (CVA), transient ischemic Attack (TIA).
- Uncontrolled hypertension defined by a SBP ≥ 160 mm Hg and/or DBP ≥ 100 mm Hg, with or without anti-hypertensive medication(s). Initiation or adjustment of antihypertensive medication(s) was allowed prior to study entry.
- +33 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (49)
Alabama Oncology
Birmingham, Alabama, 35211, United States
Highlands Oncology Group SC
Fayetteville, Arkansas, 72703, United States
PCR Oncology
Pismo Beach, California, 93449, United States
Sarcoma Oncology Center
Santa Monica, California, 90403, United States
Rocky Mountain Cancer Centers Rocky Mountain Cancer Centers
Greenwood Village, Colorado, United States
Whittingham Cancer Center Norwalk Hospital
Norwalk, Connecticut, 06856, United States
Memorial Cancer Institute Memorial Healthcare System
Hollywod, Florida, 33021, United States
Cancer Specialists of North Florida Cancer Specialists (2)
Jacksonville, Florida, 32256, United States
Florida Hospital Cancer Institute
Orlando, Florida, 32804, United States
Space Coast Medical Associates Space Coast Cancer Center
Titusville, Florida, 32796, United States
University Cancer & Blood Center, LLC
Athens, Georgia, 30607, United States
NorthWest Georgia Oncology Centers NW Georgia Oncology
Marietta, Georgia, 30060, United States
Lurie Children's Hospital of Chicago Developmental Therapeutics
Chicago, Illinois, 60611, United States
Illinois Cancer Care
Peoria, Illinois, 61615-7828, United States
Indiana University Indiana Univ. - Purdue Univ.
Indianapolis, Indiana, 46202, United States
Horizon Oncology Center Horizon Oncology Ctr.
Lafayette, Indiana, 47905, United States
St. Agnes Hospital St. Agnes Hospital (2)
Baltimore, Maryland, 21229, United States
University of Michigan Int. Medicine Oncology
Ann Arbor, Michigan, 48109, United States
Minnesota Oncology Hematology, P.A. Minnesota Oncology Hematology
Minneapolis, Minnesota, 55404, United States
Billings Clinic Onc Dept
Billings, Montana, 59107, United States
Southeast Nebraska Oncology Cancer Center
Lincoln, Nebraska, 68510, United States
Comprehensive Cancer Centers of Nevada CCC of Nevada- Southwest (2)
Las Vegas, Nevada, 89109, United States
Waverly Hematology Oncology
Cary, North Carolina, 27518, United States
Oncology Hematology Care, Inc. Oncology Hematology Care (2)
Cincinnati, Ohio, 45242, United States
Cleveland Clinic Foundation Cleveland Clinic (19)
Cleveland, Ohio, 44195, United States
St. Charles Cancer Center
Bend, Oregon, 97701, United States
Oregon Health & Science University OHSU Knight Cancer Institute
Portland, Oregon, 97239, United States
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, 15232-1305, United States
Rhode Island Hospital Rhode Island Hosp. (2)
Providence, Rhode Island, 02903, United States
Gibbs Cancer Center & Research Institute Spartanburg Reg. Healthcare
Spartanburg, South Carolina, 29303, United States
Chattanooga Oncology and Hematology Assoicates, PC Chattanooga Oncology
Chattanooga, Tennessee, 37404, United States
The West Clinic
Memphis, Tennessee, 38120, United States
Sarah Cannon Research Institute Tennessee Oncology
Nashville, Tennessee, 37203, United States
Austin Cancer Centers Austin Cancer Center (2)
Austin, Texas, 78759, United States
Texas Oncology Texas Oncology - Sammons
Dallas, Texas, 75246, United States
Texas Oncology Midtown Texas Oncology
Dallas, Texas, 75251, United States
The Center for Cancer and Blood Disorders
Fort Worth, Texas, 76104, United States
Oncology Consultants Oncology Group
Houston, Texas, 77024, United States
MD Anderson Cancer Center/University of Texas MD Anderson Cancer Center (3)
Houston, Texas, 77030, United States
Tyler Cancer Center
Tyler, Texas, 75702, United States
Intermountain Medical Center Intermountain Healthcare
Murray, Utah, 84157, United States
Virginia Cancer Specialists Virginia Cancer Specialists
Fairfax, Virginia, 22031, United States
Providence Regional Cancer Partnership Providence Reg. Cancer (2)
Everett, Washington, 98201, United States
Evergreen Hematology & Oncology
Spokane, Washington, 99218, United States
Northwest Medical Specialties Hematology/Oncology
Tacoma, Washington, 98405, United States
Wenatchee Valley Medical Center Wenatchee Valley
Wenatchee, Washington, 98801, United States
Yakima Valley Memorial Hospital North Star Lodge Cancer Center
Yakima, Washington, 98902, United States
Aurora Research Institute
Milwaukee, Wisconsin, 53226, United States
Medical College of Wisconsin Cancer Ctr.-Froedtert Hospital
Milwaukee, Wisconsin, 53226, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Novartis Pharmaceuticals
Study Officials
- STUDY DIRECTOR
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 11, 2013
First Posted
April 15, 2013
Study Start
August 1, 2013
Primary Completion
December 1, 2015
Study Completion
December 1, 2015
Last Updated
March 20, 2017
Results First Posted
March 20, 2017
Record last verified: 2017-01