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

NCT01528345 | Terminated Phase 2 Results DMC

• 2 other identifiers: CTKI258A22102011-001230-42
• Study Type: interventional
• Target: 97
• Locations: 15 countries
• Sites: 67

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.

Conditions

Metastatic Breast Cancer

Keywords

Breast Cancer; HER2-, HR+; post-menopausal; Locally advanced or metastatic Breast Cancer (HER2-, HR+)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Overall Response Rate (ORR)

  Every 8 weeks assessed up to 34 months

• 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

• Overall Survival (OS) Using Kaplan- Meier Method

  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

  Screening, Week 2, Week 4 and approximately every 4 weeks during treatment period (approximately 34 months)

• Time to Worsening of ECOG Performance Status

  Screening, Every 4 weeks during treatment period, and every 8 weeks during follow-up (approximately 9-12 months)

Study Arms (2)

Fulvestrant + Dovitinib active

EXPERIMENTAL

Fulvestrant in combination with the study drug Dovitinib.

Drug: Dovitinib; Drug: Fulvestrant

Fulvestrant + Dovitinib placebo

PLACEBO COMPARATOR

Fulvestrant in combination with a placebo matching Dovitinib.

Drug: Fulvestrant; Drug: Dovitinib Placebo

Interventions

Dovitinib DRUG

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

Also known as: TKI258

Fulvestrant + Dovitinib active

Fulvestrant DRUG

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.

Fulvestrant + Dovitinib active; Fulvestrant + Dovitinib placebo

Dovitinib Placebo DRUG

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

Fulvestrant + Dovitinib placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (67)

Ironwood Cancer and Research Centers SC

Chandler, Arizona, 85224, United States

Location

Highlands Oncology Group Dept of Highlands Oncology Grp

Fayetteville, Arkansas, 72703, United States

Location

City of Hope National Medical Center COH 3

Duarte, California, 91010-3000, United States

Location

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

La Jolla, California, 92093-0658, United States

Location

Cedars Sinai Medical Center Samuel Oschin Cancer Center

Los Angeles, California, 90048, United States

Location

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

Tampa, Florida, 33612, United States

Location

Oncology Specialists, SC Lutheran General Advanced Care

Park Ridge, Illinois, 60068-0736, United States

Location

Indiana University Health Goshen Center for Cancer SC

Goshen, Indiana, 46526, United States

Location

Nebraska Methodist Hospital Estabrook Cancer Center

Omaha, Nebraska, 68114, United States

Location

Saint Barnabas Medical Center CancerCenter of Saint Barnabas

Livingston, New Jersey, 07039, United States

Location

ProHealth Care

Lake Success, New York, 11042, United States

Location

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

Troy, New York, 12180, United States

Location

Duke University Medical Center Duke (SC)

Durham, North Carolina, 27710, United States

Location

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

Greenville, South Carolina, 29605, United States

Location

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

San Antonio, Texas, 78229, United States

Location

Virginia Cancer Specialists, PC Dept.ofFairfax SC

Fairfax, Virginia, 22031, United States

Location

Medical Oncology Associates, PS

Spokane, Washington, 99208, United States

Location

Wenatchee Valley Medical Center Wenatchee Valley

Wenatchee, Washington, 98801, United States

Location

Novartis Investigative Site

Buenos Aires, Buenos Aires, C1050AAK, Argentina

Location

Novartis Investigative Site

Córdoba, Córdoba Province, X5006IKK, Argentina

Location

Novartis Investigative Site

San Miguel de Tucumán, Tucumán Province, T4000IAK, Argentina

Location

Novartis Investigative Site

Rio Negro, Viedma, 8500, Argentina

Location

Novartis Investigative Site

Salzburg, 5020, Austria

Location

Novartis Investigative Site

Vienna, 1090, Austria

Location

Novartis Investigative Site

Leuven, 3000, Belgium

Location

Novartis Investigative Site

Wilrijk, 2610, Belgium

Location

Novartis Investigative Site

Salvador, Estado de Bahia, 40170-110, Brazil

Location

Novartis Investigative Site

Londrina, Paraná, 86015-520, Brazil

Location

Novartis Investigative Site

Porto Alegre, Rio Grande do Sul, 90610-000, Brazil

Location

Novartis Investigative Site

São José do Rio Preto, São Paulo, 15090-000, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 01317-002, Brazil

Location

Novartis Investigative Site

Besançon, 25030, France

Location

Novartis Investigative Site

Bordeaux, 33076, France

Location

Novartis Investigative Site

Lille, 59020, France

Location

Novartis Investigative Site

Saint-Herblain Cédex, 44805, France

Location

Novartis Investigative Site

Thonon-les-Bains, 74203, France

Location

Novartis Investigative Site

Villejuif, 94805, France

Location

Novartis Investigative Site

Győr, Hungary, H-9023, Hungary

Location

Novartis Investigative Site

Budapest, 1134, Hungary

Location

Novartis Investigative Site

Budapest, 1145, Hungary

Location

Novartis Investigative Site

Budapest, H-1083, Hungary

Location

Novartis Investigative Site

Debrecen, 4032, Hungary

Location

Novartis Investigative Site

Szeged, H-6720, Hungary

Location

Novartis Investigative Site

Szolnok, H-5000, Hungary

Location

Novartis Investigative Site

Macerata, MC, 62100, Italy

Location

Novartis Investigative Site

Parma, PR, 43100, Italy

Location

Novartis Investigative Site

Sondrio, SO, 23100, Italy

Location

Novartis Investigative Site

Maastricht, 6229 HX, Netherlands

Location

Novartis Investigative Site

Rotterdam, 3075 EA, Netherlands

Location

Novartis Investigative Site

Surquillo, Lima region, 34, Peru

Location

Novartis Investigative Site

Poznan, 60-569, Poland

Location

Novartis Investigative Site

Rzeszów, 35-021, Poland

Location

Novartis Investigative Site

Warsaw, 02-781, Poland

Location

Novartis Investigative Site

Warsaw, 03-291, Poland

Location

Novartis Investigative Site

Warsaw, 04-125, Poland

Location

Novartis Investigative Site

Ryazan, Russia, 390011, Russia

Location

Novartis Investigative Site

Saint Petersburg, 197758, Russia

Location

Novartis Investigative Site

Cape Town, 7500, South Africa

Location

Novartis Investigative Site

Parktown, 2193, South Africa

Location

Novartis Investigative Site

Port Elizabeth, 6045, South Africa

Location

Novartis Investigative Site

Toledo, Castille-La Mancha, 45071, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Madrid, Madrid, 28007, Spain

Location

Novartis Investigative Site

Valencia, Valencia, 46010, Spain

Location

Novartis Investigative Site

Taichung, Taichung, 407, Taiwan

Location

Novartis Investigative Site

Niaosong Township, Taiwan, 83301, Taiwan

Location

Novartis Investigative Site

Taipei, Taiwan, 10048, Taiwan

Location

Related Publications (1)

• 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.

  PMID: 28183331 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one; Fulvestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

trialandresults.registries@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2012
• First Posted: February 8, 2012
• Study Start: April 1, 2012
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: July 11, 2016
• Results First Posted: July 11, 2016

Record last verified: 2016-05

Locations

BE (2); US (18); AR (4); RU (2); BR (5); FR (6); PE (1); PL (5); AU (2); HU (7); NL (2); ZA (3); IT (3); TW (3); ES (4)