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

Primary Purpose

Metastatic Breast Cancer

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Dovitinib
Fulvestrant
Dovitinib Placebo
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Breast Cancer focused on measuring Breast Cancer, HER2-, HR+, post-menopausal, Locally advanced or metastatic Breast Cancer (HER2-, HR+)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Ironwood Cancer and Research Centers SC
  • Highlands Oncology Group Dept of Highlands Oncology Grp
  • City of Hope National Medical Center COH 3
  • University of California San Diego - Moores Cancer Center Moores UCSD Cancer Ctr. SC-1
  • Cedars Sinai Medical Center Samuel Oschin Cancer Center
  • H. Lee Moffitt Cancer Center & Research Institute H. Lee Moffitt SC
  • Oncology Specialists, SC Lutheran General Advanced Care
  • Indiana University Health Goshen Center for Cancer SC
  • Nebraska Methodist Hospital Estabrook Cancer Center
  • Saint Barnabas Medical Center CancerCenter of Saint Barnabas
  • ProHealth Care
  • New York Oncology Hematology, P.C. Dept. of New York Oncology. PC
  • Duke University Medical Center Duke (SC)
  • Cancer Centers of the Carolinas Dept. of CC of the Carolinas
  • Cancer Care Centers of South Texas / HOAST CCC of So. TX- San Antonio(2)
  • Virginia Cancer Specialists, PC Dept.ofFairfax SC
  • Medical Oncology Associates, PS
  • Wenatchee Valley Medical Center Wenatchee Valley
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
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  • Novartis Investigative Site
  • Novartis Investigative Site
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  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
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  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Fulvestrant + Dovitinib active

Fulvestrant + Dovitinib placebo

Arm Description

Fulvestrant in combination with the study drug Dovitinib.

Fulvestrant in combination with a placebo matching Dovitinib.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.)

Full Information

First Posted
January 31, 2012
Last Updated
May 26, 2016
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT01528345
Brief Title
Trial Evaluating Dovitinib Combined With Fulvestrant, in Postmenopausal Patients With HER2- and HR+ Breast Cancer
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2016
Overall Recruitment Status
Terminated
Why Stopped
Slow and low enrollment
Study Start Date
April 2012 (undefined)
Primary Completion Date
April 2015 (Actual)
Study Completion Date
April 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Breast Cancer
Keywords
Breast Cancer, HER2-, HR+, post-menopausal, Locally advanced or metastatic Breast Cancer (HER2-, HR+)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
97 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Fulvestrant + Dovitinib active
Arm Type
Experimental
Arm Description
Fulvestrant in combination with the study drug Dovitinib.
Arm Title
Fulvestrant + Dovitinib placebo
Arm Type
Placebo Comparator
Arm Description
Fulvestrant in combination with a placebo matching Dovitinib.
Intervention Type
Drug
Intervention Name(s)
Dovitinib
Other Intervention Name(s)
TKI258
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Fulvestrant
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Dovitinib Placebo
Intervention Description
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
Primary Outcome Measure Information:
Title
Progression Free Survival (PFS) Based on Local Investigator Assessment
Description
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.
Time Frame
Every 8 weeks assessed up to 34 months
Secondary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
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.
Time Frame
Every 8 weeks assessed up to 34 months
Title
Duration of Response (DOR)
Description
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.
Time Frame
From date of first documented efficacy response (CR or PR) to time of documented progression (PD) whichever comes first, assessed up to 24 months
Title
Overall Survival (OS) Using Kaplan- Meier Method
Description
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.
Time Frame
From date of randomization to date of death from any cause whichever comes first, assessed up to 34 months
Title
Number of Participants With Adverse Events as a Measure of Safety
Description
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.
Time Frame
Screening, Week 2, Week 4 and approximately every 4 weeks during treatment period (approximately 34 months)
Title
Time to Worsening of ECOG Performance Status
Description
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.)
Time Frame
Screening, Every 4 weeks during treatment period, and every 8 weeks during follow-up (approximately 9-12 months)

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Ironwood Cancer and Research Centers SC
City
Chandler
State/Province
Arizona
ZIP/Postal Code
85224
Country
United States
Facility Name
Highlands Oncology Group Dept of Highlands Oncology Grp
City
Fayetteville
State/Province
Arkansas
ZIP/Postal Code
72703
Country
United States
Facility Name
City of Hope National Medical Center COH 3
City
Duarte
State/Province
California
ZIP/Postal Code
91010-3000
Country
United States
Facility Name
University of California San Diego - Moores Cancer Center Moores UCSD Cancer Ctr. SC-1
City
La Jolla
State/Province
California
ZIP/Postal Code
92093-0658
Country
United States
Facility Name
Cedars Sinai Medical Center Samuel Oschin Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
H. Lee Moffitt Cancer Center & Research Institute H. Lee Moffitt SC
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Oncology Specialists, SC Lutheran General Advanced Care
City
Park Ridge
State/Province
Illinois
ZIP/Postal Code
60068-0736
Country
United States
Facility Name
Indiana University Health Goshen Center for Cancer SC
City
Goshen
State/Province
Indiana
ZIP/Postal Code
46526
Country
United States
Facility Name
Nebraska Methodist Hospital Estabrook Cancer Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68114
Country
United States
Facility Name
Saint Barnabas Medical Center CancerCenter of Saint Barnabas
City
Livingston
State/Province
New Jersey
ZIP/Postal Code
07039
Country
United States
Facility Name
ProHealth Care
City
Lake Success
State/Province
New York
ZIP/Postal Code
11042
Country
United States
Facility Name
New York Oncology Hematology, P.C. Dept. of New York Oncology. PC
City
Troy
State/Province
New York
ZIP/Postal Code
12180
Country
United States
Facility Name
Duke University Medical Center Duke (SC)
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Cancer Centers of the Carolinas Dept. of CC of the Carolinas
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
Facility Name
Cancer Care Centers of South Texas / HOAST CCC of So. TX- San Antonio(2)
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Virginia Cancer Specialists, PC Dept.ofFairfax SC
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Facility Name
Medical Oncology Associates, PS
City
Spokane
State/Province
Washington
ZIP/Postal Code
99208
Country
United States
Facility Name
Wenatchee Valley Medical Center Wenatchee Valley
City
Wenatchee
State/Province
Washington
ZIP/Postal Code
98801
Country
United States
Facility Name
Novartis Investigative Site
City
Rio Negro
State/Province
Viedma
ZIP/Postal Code
8500
Country
Argentina
Facility Name
Novartis Investigative Site
City
Buenos Aires
ZIP/Postal Code
C1050AAK
Country
Argentina
Facility Name
Novartis Investigative Site
City
Cordoba
ZIP/Postal Code
X5006IKK
Country
Argentina
Facility Name
Novartis Investigative Site
City
Tucuman
ZIP/Postal Code
T4000IAK
Country
Argentina
Facility Name
Novartis Investigative Site
City
Salzburg
ZIP/Postal Code
5020
Country
Austria
Facility Name
Novartis Investigative Site
City
Wien
ZIP/Postal Code
1090
Country
Austria
Facility Name
Novartis Investigative Site
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Novartis Investigative Site
City
Wilrijk
ZIP/Postal Code
2610
Country
Belgium
Facility Name
Novartis Investigative Site
City
Salvador
State/Province
BA
ZIP/Postal Code
40170-110
Country
Brazil
Facility Name
Novartis Investigative Site
City
Londrina
State/Province
PR
ZIP/Postal Code
86015-520
Country
Brazil
Facility Name
Novartis Investigative Site
City
Porto Alegre
State/Province
RS
ZIP/Postal Code
90610-000
Country
Brazil
Facility Name
Novartis Investigative Site
City
Sao Jose do Rio Preto
State/Province
SP
ZIP/Postal Code
15090-000
Country
Brazil
Facility Name
Novartis Investigative Site
City
São Paulo
State/Province
SP
ZIP/Postal Code
01317-002
Country
Brazil
Facility Name
Novartis Investigative Site
City
Besançon cedex
ZIP/Postal Code
25030
Country
France
Facility Name
Novartis Investigative Site
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Facility Name
Novartis Investigative Site
City
Lille Cedex
ZIP/Postal Code
59020
Country
France
Facility Name
Novartis Investigative Site
City
Saint-Herblain Cédex
ZIP/Postal Code
44805
Country
France
Facility Name
Novartis Investigative Site
City
Thonon-les-Bains Cedex
ZIP/Postal Code
74203
Country
France
Facility Name
Novartis Investigative Site
City
Villejuif Cedex
ZIP/Postal Code
94805
Country
France
Facility Name
Novartis Investigative Site
City
Budapest
ZIP/Postal Code
1134
Country
Hungary
Facility Name
Novartis Investigative Site
City
Budapest
ZIP/Postal Code
1145
Country
Hungary
Facility Name
Novartis Investigative Site
City
Budapest
ZIP/Postal Code
H-1083
Country
Hungary
Facility Name
Novartis Investigative Site
City
Debrecen
ZIP/Postal Code
4032
Country
Hungary
Facility Name
Novartis Investigative Site
City
Gyor
ZIP/Postal Code
H-9023
Country
Hungary
Facility Name
Novartis Investigative Site
City
Szeged
ZIP/Postal Code
H-6720
Country
Hungary
Facility Name
Novartis Investigative Site
City
Szolnok
ZIP/Postal Code
H-5000
Country
Hungary
Facility Name
Novartis Investigative Site
City
Macerata
State/Province
MC
ZIP/Postal Code
62100
Country
Italy
Facility Name
Novartis Investigative Site
City
Parma
State/Province
PR
ZIP/Postal Code
43100
Country
Italy
Facility Name
Novartis Investigative Site
City
Sondrio
State/Province
SO
ZIP/Postal Code
23100
Country
Italy
Facility Name
Novartis Investigative Site
City
Maastricht
ZIP/Postal Code
6229 HX
Country
Netherlands
Facility Name
Novartis Investigative Site
City
Rotterdam
ZIP/Postal Code
3075 EA
Country
Netherlands
Facility Name
Novartis Investigative Site
City
Surquillo
State/Province
Lima
ZIP/Postal Code
34
Country
Peru
Facility Name
Novartis Investigative Site
City
Poznan
ZIP/Postal Code
60-569
Country
Poland
Facility Name
Novartis Investigative Site
City
Rzeszow
ZIP/Postal Code
35-021
Country
Poland
Facility Name
Novartis Investigative Site
City
Warszawa
ZIP/Postal Code
02-781
Country
Poland
Facility Name
Novartis Investigative Site
City
Warszawa
ZIP/Postal Code
03-291
Country
Poland
Facility Name
Novartis Investigative Site
City
Warszawa
ZIP/Postal Code
04-125
Country
Poland
Facility Name
Novartis Investigative Site
City
Ryazan
State/Province
Russia
ZIP/Postal Code
390011
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
St. Petersburg
ZIP/Postal Code
197758
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Cape Town
ZIP/Postal Code
7500
Country
South Africa
Facility Name
Novartis Investigative Site
City
Parktown
ZIP/Postal Code
2193
Country
South Africa
Facility Name
Novartis Investigative Site
City
Port Elizabeth
ZIP/Postal Code
6045
Country
South Africa
Facility Name
Novartis Investigative Site
City
Toledo
State/Province
Castilla la Mancha
ZIP/Postal Code
45071
Country
Spain
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08035
Country
Spain
Facility Name
Novartis Investigative Site
City
Valencia
State/Province
Comunidad Valenciana
ZIP/Postal Code
46010
Country
Spain
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Facility Name
Novartis Investigative Site
City
Niaosong Township
ZIP/Postal Code
83301
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Taichung
ZIP/Postal Code
407
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Taipei
ZIP/Postal Code
10048
Country
Taiwan

12. IPD Sharing Statement

Citations:
PubMed Identifier
28183331
Citation
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.
Results Reference
derived

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

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