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

Phase 2
Terminated
Conditions
Metastatic Breast Cancer
Interventions
Registration Number
NCT01528345
Lead Sponsor
Novartis Pharmaceuticals
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
Female
Target Recruitment
97
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Fulvestrant + Dovitinib placeboDovitinib PlaceboFulvestrant in combination with a placebo matching Dovitinib.
Fulvestrant + Dovitinib activeFulvestrantFulvestrant in combination with the study drug Dovitinib.
Fulvestrant + Dovitinib placeboFulvestrantFulvestrant in combination with a placebo matching Dovitinib.
Fulvestrant + Dovitinib activeDovitinibFulvestrant in combination with the study drug Dovitinib.
Primary Outcome Measures
NameTimeMethod
Progression Free Survival (PFS) Based on Local Investigator AssessmentEvery 8 weeks assessed up to 34 months

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
NameTimeMethod
Number of Participants With Adverse Events as a Measure of SafetyScreening, Week 2, Week 4 and approximately every 4 weeks during treatment period (approximately 34 months)

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.

Overall Response Rate (ORR)Every 8 weeks assessed up to 34 months

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)From date of first documented efficacy response (CR or PR) to time of documented progression (PD) whichever comes first, assessed up to 24 months

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 to Worsening of ECOG Performance StatusScreening, Every 4 weeks during treatment period, and every 8 weeks during follow-up (approximately 9-12 months)

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.)

Overall Survival (OS) Using Kaplan- Meier MethodFrom date of randomization to date of death from any cause whichever comes first, assessed up to 34 months

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.

Trial Locations

Locations (19)

City of Hope National Medical Center COH 3

🇺🇸

Duarte, California, United States

University of California San Diego - Moores Cancer Center Moores UCSD Cancer Ctr. SC-1

🇺🇸

La Jolla, California, United States

ProHealth Care

🇺🇸

Lake Success, New York, United States

Indiana University Health Goshen Center for Cancer SC

🇺🇸

Goshen, Indiana, United States

New York Oncology Hematology, P.C. Dept. of New York Oncology. PC

🇺🇸

Troy, New York, United States

Medical Oncology Associates, PS

🇺🇸

Spokane, Washington, United States

Novartis Investigative Site

🇨🇳

Taipei, Taiwan

Ironwood Cancer and Research Centers SC

🇺🇸

Chandler, Arizona, United States

Cancer Centers of the Carolinas Dept. of CC of the Carolinas

🇺🇸

Greenville, South Carolina, United States

Highlands Oncology Group Dept of Highlands Oncology Grp

🇺🇸

Fayetteville, Arkansas, United States

Cedars Sinai Medical Center Samuel Oschin Cancer Center

🇺🇸

Los Angeles, California, United States

H. Lee Moffitt Cancer Center & Research Institute H. Lee Moffitt SC

🇺🇸

Tampa, Florida, United States

Oncology Specialists, SC Lutheran General Advanced Care

🇺🇸

Park Ridge, Illinois, United States

Nebraska Methodist Hospital Estabrook Cancer Center

🇺🇸

Omaha, Nebraska, United States

Saint Barnabas Medical Center CancerCenter of Saint Barnabas

🇺🇸

Livingston, New Jersey, United States

Duke University Medical Center Duke (SC)

🇺🇸

Durham, North Carolina, United States

Cancer Care Centers of South Texas / HOAST CCC of So. TX- San Antonio(2)

🇺🇸

San Antonio, Texas, United States

Wenatchee Valley Medical Center Wenatchee Valley

🇺🇸

Wenatchee, Washington, United States

Virginia Cancer Specialists, PC Dept.ofFairfax SC

🇺🇸

Fairfax, Virginia, United States

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