Study of Combined Fulvestrant and Everolimus in Advanced/Metastatic Breast Cancer After Aromatase Inhibitor Failure

NCT00570921 | Completed Phase 2 Results DMC

• 1 other identifier: 07-BRE-43-NP
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to determine if estrogen receptor-targeted therapy with fulvestrant used in combination with Everolimus is an effective and safe therapy for women with hormone receptor positive metastatic breast cancer after failure of aromatase inhibitor therapy.

Conditions

Breast Cancer

Keywords

Breast cancer; Fulvestrant; Everolimus

Outcome Measures

Primary Outcomes (1)

• Time to Progression

  Duration of time start of treatment to time of documented progression or death

Secondary Outcomes (2)

• Objective Response Rates

  Evaluated 60 days after therapy start

• Clinical Benefit Rate

  Duration of response or stable disease for 24 weeks or more

Study Arms (1)

Fulvestrant + Everolimus

EXPERIMENTAL

Fulvestrant + Everolimus Fulvestrant was administered intramuscularly (in the gluteus maximus) in a loading dose schedule as follows: 500 mg in two divided doses-one on each side on day 1, then 250 mg on day 14, and then 250 mg on day 28 and every 4 weeks ± 3 days thereafter. Everolimus was administered initially at a dose of 5 mg daily in the first 5-patient cohort for the first month of treatment and then increased to 10 mg PO daily after that.

Drug: Everolimus; Drug: Fulvestrant

Interventions

Everolimus DRUG

Everolimus tablets, two-5 mg tablets a day

Also known as: RAD001

Fulvestrant + Everolimus

Fulvestrant DRUG

intramuscular, 500 mg in two divided doses- one on each side- on day 1, then 250mg on day 14, then 250 mg on day 28 and every 4 weeks +/- 3 days thereafter

Also known as: Faslodex

Fulvestrant + Everolimus

Eligibility Criteria

• Age: 45 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Postmenopausal status, defined as any one of the following criteria: Documented history of bilateral oophorectomy, Age 60 years or more, OR Age 45 to 59 and satisfying one or more of the following criteria: Amenorrhea for at least 12 months and intact uterus OR Amenorrhea for less than 12 months and a follicle stimulating hormone (FSH) concentration - within postmenopausal range including: Patients who have had a hysterectomy or Patients who have received hormone replacement
• Patients must have histologically confirmed invasive breast cancer
• Metastatic or locally advanced disease
• Patients must have estrogen receptor and/or progesterone receptor positive disease
• Measurable or evaluable disease
• Failure of aromatase inhibitor therapy within the previous 6 months. Patients who received prior tamoxifen are eligible to enroll
• Prior aromatase inhibitor therapy or other endocrine therapy must be discontinued at least 1 week prior to enrollment and any toxicity from such therapy must have reverted to grade I or less at the time of enrollment
• Patients must not have received chemotherapy, radiation therapy, or had surgery within 4 weeks prior to enrollment and any toxicity from such therapy must have recovered to grade 1 or less prior to enrollment
• Patients must not have received either of the study medications previously
• WHO performance status of 0, 1, or 2
• Adequate organ function defined as follows: Adequate renal function, defined by a serum creatinine within the upper limits of normal, Adequate liver function, defined by a bilirubin of \< 1.5 the upper limit of normal (ULN) and aspartate aminotransferase (AST), alanine aminotransferase (ALT) of ≤ 2.5 times the ULN, Adequate bone marrow function, defined as an absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelet count (PLT) \>100,000/ul, Hb \>9 gm/dl, international normalized ratio (INR) \<1.3, and because fulvestrant is administered intramuscularly, it should not be used in patients with bleeding diatheses, thrombocytopenia or in patients on anticoagulants
• Patients will be asked to provide a tumor paraffin block if available
• Ability to understand and sign a written informed consent for participation in the trial

You may not qualify if:

• Known severe hypersensitivity to everolimus (or similar drugs) or any of the excipients of this product
• Premenopausal status
• Other coexisting malignancies with the exception of basal cell carcinoma or cervical cancer in situ
• Patients with brain metastasis or leptomeningeal involvement
• Patients with malignant pleural effusion or ascites only disease
• Rapidly progressive visceral disease
• WHO performance status of 3 or 4
• As judged by the investigator, uncontrolled intercurrent illness including, but not limited to: Ongoing or active infection, Symptomatic congestive heart failure, Unstable angina pectoris or significant cardiac arrhythmia, Psychiatric illness/social situations that would limit compliance with study requirements, Severely impaired lung function such as severe chronic obstructive pulmonary disease (COPD) or interstitial lung disease, a known forced expiratory volume at one second (FEV1) of \< 1.5 liters, or dyspnea of grade III or greater, Uncontrolled diabetes as defined by a fasting blood sugar (FBS) of \> 1.5 ULM, Known liver disease such as cirrhosis or chronic hepatitis, Known HIV positivity, OR known condition causing malabsorption
• Chronic treatment with systemic steroids or other immunosuppressive agents
• Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period
• Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the subject to participate in the clinical trial
• Prior treatment with an mTOR inhibitor
• Treatment with a non-approved or investigational drug within 30 days or 5 half-lives of the drug, whichever is greater, before Day 1 of study treatment
• In the opinion of the investigator, bleeding diathesis or anticoagulation therapy that would preclude intramuscular injections
• History of hypersensitivity to castor oil

Sponsors & Collaborators

• Mara Chambers: lead
• Novartis: collaborator

Study Sites (1)

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Related Publications (1)

• Massarweh S, Romond E, Black EP, Van Meter E, Shelton B, Kadamyan-Melkumian V, Stevens M, Elledge R. A phase II study of combined fulvestrant and everolimus in patients with metastatic estrogen receptor (ER)-positive breast cancer after aromatase inhibitor (AI) failure. Breast Cancer Res Treat. 2014 Jan;143(2):325-32. doi: 10.1007/s10549-013-2810-9. Epub 2013 Dec 11.

  PMID: 24327334 RESULT

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Everolimus; Fulvestrant

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Limitations and Caveats

Potential toxicities of mammalian target of rapamycin (mTOR) inhibitors and our observation that a third of patients had no benefit from this strategy, we need to identify biomarkers that correlate with treatment benefit for better patient selection.

Results Point of Contact

• Title: Dr. Mara D. Chambers
• Organization: University of Kentucky

mdcham2@email.uky.edu

866-340-4488

Study Officials

• Mara Chambers, M.D.

  University of Kentucky

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: December 7, 2007
• First Posted: December 11, 2007
• Study Start: April 1, 2008
• Primary Completion: February 1, 2013
• Study Completion: January 1, 2015
• Last Updated: February 23, 2017
• Results First Posted: December 31, 2014

Record last verified: 2017-01

Locations

US (1)