Trial Evaluating Dovitinib Combined With Fulvestrant, in Postmenopausal Patients With HER2- and HR+ Breast Cancer

A Multicenter, Randomized, Double Blind, Placebo Controlled, Phase II Trial Evaluating the Safety and Efficacy of Dovitinib Combined With Fulvestrant, in Postmenopausal Patients With HER2- and HR+ Breast Cancer That Have Evidence of Disease Progression on or After Prior Endocrine Therapy

This trial is designed to enroll postmenopausal patients with locally advanced or metastatic, HER2- and HR+ breast cancer not amenable to curative treatment by surgery or radiotherapy, and whose disease has progressed on or after prior endocrine therapy.

Patients must undergo molecular pre-screening prior to entry.

Study Overview

• Status: Terminated
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: Dovitinib; Drug: Fulvestrant; Drug: Dovitinib Placebo

• Study Type: Interventional
• Enrollment (Actual): 97
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1050AAK
    • Novartis Investigative Site
  • Cordoba, Argentina, X5006IKK
    • Novartis Investigative Site
  • Tucuman, Argentina, T4000IAK
    • Novartis Investigative Site
  • Viedma
    • Rio Negro, Viedma, Argentina, 8500
      • Novartis Investigative Site
• Austria
  • Salzburg, Austria, 5020
    • Novartis Investigative Site
  • Wien, Austria, 1090
    • Novartis Investigative Site
• Belgium
  • Leuven, Belgium, 3000
    • Novartis Investigative Site
  • Wilrijk, Belgium, 2610
    • Novartis Investigative Site
• Brazil
  • BA
    • Salvador, BA, Brazil, 40170-110
      • Novartis Investigative Site
  • PR
    • Londrina, PR, Brazil, 86015-520
      • Novartis Investigative Site
  • RS
    • Porto Alegre, RS, Brazil, 90610-000
      • Novartis Investigative Site
  • SP
    • Sao Jose do Rio Preto, SP, Brazil, 15090-000
      • Novartis Investigative Site
    • São Paulo, SP, Brazil, 01317-002
      • Novartis Investigative Site
• France
  • Besançon cedex, France, 25030
    • Novartis Investigative Site
  • Bordeaux, France, 33076
    • Novartis Investigative Site
  • Lille Cedex, France, 59020
    • Novartis Investigative Site
  • Saint-Herblain Cédex, France, 44805
    • Novartis Investigative Site
  • Thonon-les-Bains Cedex, France, 74203
    • Novartis Investigative Site
  • Villejuif Cedex, France, 94805
    • Novartis Investigative Site
• Hungary
  • Budapest, Hungary, 1145
    • Novartis Investigative Site
  • Budapest, Hungary, 1134
    • Novartis Investigative Site
  • Budapest, Hungary, H-1083
    • Novartis Investigative Site
  • Debrecen, Hungary, 4032
    • Novartis Investigative Site
  • Gyor, Hungary, H-9023
    • Novartis Investigative Site
  • Szeged, Hungary, H-6720
    • Novartis Investigative Site
  • Szolnok, Hungary, H-5000
    • Novartis Investigative Site
• Italy
  • MC
    • Macerata, MC, Italy, 62100
      • Novartis Investigative Site
  • PR
    • Parma, PR, Italy, 43100
      • Novartis Investigative Site
  • SO
    • Sondrio, SO, Italy, 23100
      • Novartis Investigative Site
• Netherlands
  • Maastricht, Netherlands, 6229 HX
    • Novartis Investigative Site
  • Rotterdam, Netherlands, 3075 EA
    • Novartis Investigative Site
• Peru
  • Lima
    • Surquillo, Lima, Peru, 34
      • Novartis Investigative Site
• Poland
  • Poznan, Poland, 60-569
    • Novartis Investigative Site
  • Rzeszow, Poland, 35-021
    • Novartis Investigative Site
  • Warszawa, Poland, 02-781
    • Novartis Investigative Site
  • Warszawa, Poland, 04-125
    • Novartis Investigative Site
  • Warszawa, Poland, 03-291
    • Novartis Investigative Site
• Russian Federation
  • St. Petersburg, Russian Federation, 197758
    • Novartis Investigative Site
  • Russia
    • Ryazan, Russia, Russian Federation, 390011
      • Novartis Investigative Site
• South Africa
  • Cape Town, South Africa, 7500
    • Novartis Investigative Site
  • Parktown, South Africa, 2193
    • Novartis Investigative Site
  • Port Elizabeth, South Africa, 6045
    • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28007
    • Novartis Investigative Site
  • Castilla la Mancha
    • Toledo, Castilla la Mancha, Spain, 45071
      • Novartis Investigative Site
  • Catalunya
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site
  • Comunidad Valenciana
    • Valencia, Comunidad Valenciana, Spain, 46010
      • Novartis Investigative Site
• Taiwan
  • Niaosong Township, Taiwan, 83301
    • Novartis Investigative Site
  • Taichung, Taiwan, 407
    • Novartis Investigative Site
  • Taipei, Taiwan, 10048
    • Novartis Investigative Site
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Ironwood Cancer and Research Centers SC
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Highlands Oncology Group Dept of Highlands Oncology Grp
  • California
    • Duarte, California, United States, 91010-3000
      • City of Hope National Medical Center COH 3
    • La Jolla, California, United States, 92093-0658
      • University of California San Diego - Moores Cancer Center Moores UCSD Cancer Ctr. SC-1
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center Samuel Oschin Cancer Center
  • Florida
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center & Research Institute H. Lee Moffitt SC
  • Illinois
    • Park Ridge, Illinois, United States, 60068-0736
      • Oncology Specialists, SC Lutheran General Advanced Care
  • Indiana
    • Goshen, Indiana, United States, 46526
      • Indiana University Health Goshen Center for Cancer SC
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Nebraska Methodist Hospital Estabrook Cancer Center
  • New Jersey
    • Livingston, New Jersey, United States, 07039
      • Saint Barnabas Medical Center CancerCenter of Saint Barnabas
  • New York
    • Lake Success, New York, United States, 11042
      • ProHealth Care
    • Troy, New York, United States, 12180
      • New York Oncology Hematology, P.C. Dept. of New York Oncology. PC
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center Duke (SC)
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Cancer Centers of the Carolinas Dept. of CC of the Carolinas
  • Texas
    • San Antonio, Texas, United States, 78229
      • Cancer Care Centers of South Texas / HOAST CCC of So. TX- San Antonio(2)
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists, PC Dept.ofFairfax SC
  • Washington
    • Spokane, Washington, United States, 99208
      • Medical Oncology Associates, PS
    • Wenatchee, Washington, United States, 98801
      • Wenatchee Valley Medical Center Wenatchee Valley

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Postmenopausal women with HER2-, HR+ locally advanced or metastatic breast cancer
• Progression on or after endocrine treatment
• Measureable disease as per RECIST
• ECOG 0, 1 or 2

Exclusion Criteria:

• Evidence of CNS or leptomeningeal metastases
• Previous treatment with fulvestrant
• Previous chemotherapy for locally advanced or metastatic breast cancer
• Cirrhosis or chronic active/persistent hepatitis

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fulvestrant + Dovitinib active; Fulvestrant in combination with the study drug Dovitinib.	Drug: Dovitinib; Active Dovitinib (in tablet form) taken orally at a dose of 500 mg (i.e., 5 x 100mg tablets) on a 5 days on/2 days off dosing schedule; Other Names: TKI258; Drug: Fulvestrant; Fulvestrant (in solution) injected intramuscularly at a dose of 500 mg once on Week 1 Day 1, Week 3 Day 1 and Week 5 Day 1 and subsequently once every 4 weeks on Day 1 of the week.
Placebo Comparator: Fulvestrant + Dovitinib placebo; Fulvestrant in combination with a placebo matching Dovitinib.	Drug: Fulvestrant; Fulvestrant (in solution) injected intramuscularly at a dose of 500 mg once on Week 1 Day 1, Week 3 Day 1 and Week 5 Day 1 and subsequently once every 4 weeks on Day 1 of the week.; Drug: Dovitinib Placebo; Dovitinib Placebo (in tablet form) taken orally at a dose of 500 mg (i.e., 5 x 100mg tablets) on a 5 days on/2 days off dosing schedule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) Based on Local Investigator Assessment	PFS was defined as the time from the date of randomization to the date of the first radiologically documented disease progression or death due to any cause and was assessed based on RECIST v1.1. Responses include: Complete Response: Disappearance of all non-nodal target lesions; Partial Response: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters; Progressive Disease: At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline; Stable Disease: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD; Unknown (UNK) Progression has not been documented and one or more target lesions have not been assessed or have been assessed using a different method than baseline.	Every 8 weeks assessed up to 34 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	ORR was defined as the percentage of patients with a best overall response of Complete Response (CR) or Partial Response (PR) as per RECIST v1.1. Responses include: Complete Response: Disappearance of all non-nodal target lesions; Partial Response: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters; Progressive Disease: At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline; Stable Disease: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD; Unknown (UNK) Progression has not been documented and one or more target lesions have not been assessed or have been assessed using a different method than baseline.	Every 8 weeks assessed up to 34 months
Duration of Response (DOR)	DOR was defined as time from the date of the first documented response (CR or PR) to the date of the first documented or death due to disease. If a patient does not have a progression event, DOR will be censored on the date of the last adequate tumor assessment.	From date of first documented efficacy response (CR or PR) to time of documented progression (PD) whichever comes first, assessed up to 24 months
Overall Survival (OS) Using Kaplan- Meier Method	OS was defined as the time from the date of randomization to the date of death from any cause. If a patient is not known to have died at the date of analysis cut-off, the OS will be censored at the last date of contact.	From date of randomization to date of death from any cause whichever comes first, assessed up to 34 months
Number of Participants With Adverse Events as a Measure of Safety	The type, frequency and severity of adverse events, laboratory values, and Electrocardiograms (ECGs) experienced by patients will be assessed according to Common Terminology Criteria for Adverse Events. The study enrollment was terminated early due to challenges in enrolling patients with FGF amplified status. See safety section for safety details.	Screening, Week 2, Week 4 and approximately every 4 weeks during treatment period (approximately 34 months)
Time to Worsening of ECOG Performance Status	Eastern Cooperative Oncology Group (ECOG) Performance Status (scales and criteria used by doctors and researchers to assess how a patient's disease is progressing and assess how the disease affects the daily living abilities of the patient.)	Screening, Every 4 weeks during treatment period, and every 8 weeks during follow-up (approximately 9-12 months)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Musolino A, Campone M, Neven P, Denduluri N, Barrios CH, Cortes J, Blackwell K, Soliman H, Kahan Z, Bonnefoi H, Squires M, Zhang Y, Deudon S, Shi MM, Andre F. Phase II, randomized, placebo-controlled study of dovitinib in combination with fulvestrant in postmenopausal patients with HR+, HER2- breast cancer that had progressed during or after prior endocrine therapy. Breast Cancer Res. 2017 Feb 10;19(1):18. doi: 10.1186/s13058-017-0807-8.

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: January 31, 2012
• First Submitted That Met QC Criteria: February 7, 2012
• First Posted (Estimate): February 8, 2012

Study Record Updates

• Last Update Posted (Estimate): July 11, 2016
• Last Update Submitted That Met QC Criteria: May 26, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: Breast Cancer; post-menopausal; HER2-, HR+; Locally advanced or metastatic Breast Cancer (HER2-, HR+)
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Estrogen Antagonists; Estrogen Receptor Antagonists; Fulvestrant
• Other Study ID Numbers: CTKI258A2210; 2011-001230-42 (EudraCT Number)