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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Metastatic Breast Cancer

Intervention / Treatment
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* Drug: Dovitinib
* Drug: Fulvestrant
* Drug: Dovitinib Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fulvestrant + Dovitinib active<br>Fulvestrant in combination with the study drug Dovitinib. | Drug: Dovitinib<br>* 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<br>* Other names: TKI258;Drug: Fulvestrant<br>* 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.<br>|
| Placebo Comparator: Fulvestrant + Dovitinib placebo<br>Fulvestrant in combination with a placebo matching Dovitinib. | Drug: Fulvestrant<br>* 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.<br>Drug: Dovitinib Placebo<br>* 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<br>|

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Cancer, HER2-, HR+, post-menopausal, Locally advanced or metastatic Breast Cancer (HER2-, HR+)