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

This study has been terminated.
(Slow and low enrollment)
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01528345
First received: January 31, 2012
Last updated: May 26, 2016
Last verified: May 2016
  Purpose

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.


Condition Intervention Phase
Metastatic Breast Cancer
Drug: Dovitinib
Drug: Fulvestrant
Drug: Dovitinib Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Progression Free Survival (PFS) Based on Local Investigator Assessment [ Time Frame: Every 8 weeks assessed up to 34 months ] [ Designated as safety issue: No ]
    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) [ Time Frame: Every 8 weeks assessed up to 34 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: Yes ]

    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) ] [ Designated as safety issue: No ]
    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.)


Enrollment: 97
Study Start Date: April 2012
Study Completion Date: April 2015
Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 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.
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

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01528345

  Show 67 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01528345     History of Changes
Other Study ID Numbers: CTKI258A2210  2011-001230-42 
Study First Received: January 31, 2012
Results First Received: April 1, 2016
Last Updated: May 26, 2016
Health Authority: United States: Food and Drug Administration
Argentina: Ministry of Health
Austria: Federal Ministry for Health and Women
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Brazil: Ministry of Health
Egypt: Ministry of Health and Population
France: Agence française de sécurité sanitaire des produits de santé (Afssaps)
Hungary: National Institute of Pharmacy
Israel: Ministry of Health
Italy: Italian Pharmaceutical Agency (AIFA)
Netherlands: Medicines Evaluation Board (MEB)
Peru: National Health Institute
Poland: Ministry of Health
Russia: Pharmacological Committee, Ministry of Health
South Africa: Department of Health
Spain: Medicines and Health Products Agency (AEMPS)
Taiwan: Department of Health

Keywords provided by Novartis:
Breast Cancer
HER2-, HR+
post-menopausal
Locally advanced or metastatic Breast Cancer (HER2-, HR+)

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Fulvestrant
Estradiol
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Estrogen Receptor Antagonists
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Estrogens
Hormones

ClinicalTrials.gov processed this record on September 30, 2016