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

• ClinicalTrials.gov Identifier: NCT01528345
• Recruitment Status: Terminated
• First Posted: February 8, 2012
• Results First Posted: July 11, 2016
• Last Update Posted: July 11, 2016
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Tracking Information

• First Submitted Date: January 31, 2012
• First Posted Date: February 8, 2012
• Results First Submitted Date: April 1, 2016
• Results First Posted Date: July 11, 2016
• Last Update Posted Date: July 11, 2016
• Study Start Date: April 2012
• Actual Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 26, 2016)

Progression Free Survival (PFS) Based on Local Investigator Assessment [ Time Frame: Every 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.

Original Primary Outcome Measures (submitted: February 7, 2012)

Time to Progression Free Survival (PFS) [ Time Frame: From date of randomization to disease progression or death (up to 24 months) ]

PFS is defined as the date of randomization to the date of the first radiologically documented disease progression (PD) or death due to any cause per local investigator assessment as per RECIST.

Current Secondary Outcome Measures (submitted: May 26, 2016)

• Overall Response Rate (ORR) [ Time Frame: 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) [ 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 ]
  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 [ Time Frame: From 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.
• Number of Participants With Adverse Events as a Measure of Safety [ Time Frame: Screening, 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.
• Time to Worsening of ECOG Performance Status [ Time Frame: Screening, 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.)

Original Secondary Outcome Measures (submitted: February 7, 2012)

• Overall Response Rate (ORR) [ Time Frame: Every 8 weeks assessed up to 24 months ]
  ORR is defined as the percentage of patients with a best overall response of Complete Response (CR) or Partial Response (PR) as per RECIST
• Duration of Response (DOR) [ 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 ]
  DOR is 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) [ Time Frame: From date of randomization to date of death from any cause whichever comes first, assessed up to 24 months ]
  OS is 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.
• Safety (type, frequency and severity of adverse events, and laboratory values) [ Time Frame: Screening, Week 2, Week 4 and approximately every 4 weeks during treatment period (approximately 6-9 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
• 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) ]
  The time to worsening of ECOG performance status will be measured.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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

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 Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Single Group Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Metastatic Breast Cancer

Intervention

• 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 Name: 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.
• 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

Study Arms

• Experimental: Fulvestrant + Dovitinib active
  Fulvestrant in combination with the study drug Dovitinib.
  Interventions:

  • Drug: Dovitinib
  • Drug: Fulvestrant
• Placebo Comparator: Fulvestrant + Dovitinib placebo
  Fulvestrant in combination with a placebo matching Dovitinib.
  Interventions:

  • Drug: Fulvestrant
  • Drug: Dovitinib Placebo

• 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.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: June 19, 2015): 97
• Original Estimated Enrollment (submitted: February 7, 2012): 150
• Actual Study Completion Date: April 2015
• Actual Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Austria, Belgium, Brazil, France, Hungary, Italy, Netherlands, Peru, Poland, Russian Federation, South Africa, Spain, Taiwan, United States
• Removed Location Countries: China, Egypt

Administrative Information

• NCT Number: NCT01528345
• Other Study ID Numbers: CTKI258A2210; 2011-001230-42 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Novartis ( Novartis Pharmaceuticals )
• Original Responsible Party: Same as current
• Current Study Sponsor: Novartis Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

• PRS Account: Novartis
• Verification Date: May 2016