Phase II Study of Everolimus Beyond Progression

NCT02269670 | Terminated Phase 2 Results DMC

• 3 other identifiers: IRB00071229NCI-2014-02092WINSHIP2563-13
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 3

Brief Summary

This phase II trial studies how well everolimus and hormone therapy work in treating patients with hormone receptor positive breast cancer that has continued to spread (progressed) or returned after a period of improvement (recurred) on everolimus and exemestane hormone therapy. Everolimus is a chemotherapy drug that may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Estrogen and progesterone are hormones that can cause the growth of breast cancer cells. Hormone therapy may fight breast cancer by lowering the amount of estrogen and progesterone the body makes. Giving everolimus with a different type of hormone therapy may be an effective treatment for breast cancer in patients who progressed on everolimus with exemestane.

Conditions

Estrogen Receptor-positive Breast Cancer; HER2-negative Breast Cancer; Progesterone Receptor-positive Breast Cancer; Recurrent Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Response Rate (Partial Response Plus Complete Response) Using RECIST

  Study was terminated early due to difficulties with enrollment. No outcome measures were assessed.

  Up to 2 years

• Progression-free Survival (PFS)

  Study was terminated early due to difficulties with enrollment. No outcome measures were assessed.

  Up to 2 years

Secondary Outcomes (3)

• Clinical Benefit Rate (Response Rate Plus Stable Disease)

  Up to 2 years

• Overall Survival (OS)

  From the initiation of alternate hormonal treatment in combination with everolimus to time of death from any cause, assessed up to 2 years

• Incidence of Adverse Events Assessed Using Common Terminology Criteria for Adverse Events Version 4.0

  Up to 2 years

Study Arms (1)

Treatment (everolimus, hormone therapy)

EXPERIMENTAL

Patients receive everolimus PO daily and a hormone therapy regimen chosen at the discretion of the investigator (anastrozole PO daily; letrozole PO daily; tamoxifen citrate PO daily; fulvestrant IM or PO on days 1, 15, and 29, and then monthly; megestrol acetate PO QID; or other regimen). Treatment continues in the absence of disease progression or unacceptable toxicity.

Drug: everolimus; Drug: anastrozole; Drug: letrozole; Drug: tamoxifen citrate; Drug: fulvestrant; Drug: megestrol acetate

Interventions

everolimus DRUG

Given PO

Also known as: 42-O-(2-hydroxy)ethyl rapamycin, Afinitor, RAD001

Treatment (everolimus, hormone therapy)

anastrozole DRUG

Given PO

Also known as: ANAS, Arimidex, ICI-D1033

Treatment (everolimus, hormone therapy)

letrozole DRUG

Given PO

Also known as: CGS 20267, Femara, LTZ

Treatment (everolimus, hormone therapy)

tamoxifen citrate DRUG

Given PO

Also known as: Nolvadex, TAM, tamoxifen, TMX

Treatment (everolimus, hormone therapy)

fulvestrant DRUG

Given IM or PO

Also known as: Faslodex, ICI 182,780

Treatment (everolimus, hormone therapy)

megestrol acetate DRUG

Given PO

Also known as: BDH 1298, Maygace, Megace, Megestil, Niagestin

Treatment (everolimus, hormone therapy)

Eligibility Criteria

• Age: 19 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Estrogen (ER) and/or progesterone (PR)-positive at primary diagnosis and at metastatic diagnosis where tissue is available (defined as \> or = 1% of staining nuclei)
• Progressive or recurrent breast cancer defined as disease progression or recurrence while on a combination of exemestane with everolimus
• Human epidermal growth factor receptor 2 (HER2)/neu-negative breast cancer by standard criteria (immunohistochemistry \[IHC\] \< 3+ or fluorescence in situ hybridization \[FISH\] negative if IHC 2+) at primary diagnosis
• Histologically confirmed, measurable or evaluable disease; patients should have at least one measurable lesion; if applicable, Response Evaluation Criteria in Solid Tumors (RECIST) criteria should be used
• Life expectancy \> 6 months
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Absolute neutrophil count (ANC) \> 1,500/µL
• Platelets ≥ 100,000/µL
• Hemoglobin \> 10 g/dL
• Creatinine ≤ 1.5 x upper limit of normal (ULN)
• Bilirubin ≤ 1.5 x ULN
• International normalized ratio ≤ 1.3 (or ≤ 3 on anticoagulants)
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \< 2 x ULN unless related to primary disease
• Signed informed consent
• Adequate birth control

You may not qualify if:

• Prior treatment with everolimus other than in combination with hormonal therapy for treatment of breast cancer or prior treatment with another mammalian target of rapamycin (mTOR) inhibitor (sirolimus, temsirolimus) for any indication
• HER2 positive disease as defined by 3+ IHC or positive FISH (both in primary and metastatic sites)
• Active infection: temperature \> 100 Fahrenheit (F), fever of unknown origin, active symptoms or signs of infection as defined by the investigator
• Uncontrolled central nervous system metastases
• Life-threatening, visceral metastases
• Pregnant or lactating women
• Prior chemotherapy within the last 4 weeks
• Prior radiation therapy within the last 4 weeks; prior radiation therapy to indicator lesion (unless objective disease recurrence or progression within the radiation portal has been documented since completion of radiation)
• Concomitant malignancies or previous malignancies within the last 5 years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
• History of significant cardiac disease, cardiac risk factors or uncontrolled arrhythmias
• Hypersensitivity to trial medications (everolimus)
• Emotional limitations, which the investigator judges could limit the patient's ability to follow up and comply with study procedures
• Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent
• Uncontrolled diabetes as defined by fasting serum glucose \> 1.5 x ULN
• Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis

Sponsors & Collaborators

• Emory University: lead
• Novartis: collaborator

Study Sites (3)

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

Location

Emory University/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Emory Saint Joseph's Hospital

Atlanta, Georgia, 30342, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Everolimus; Anastrozole; Letrozole; Tamoxifen; Fulvestrant; Megestrol Acetate

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Nitriles; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Megestrol; Pregnadienes; Pregnanes

Limitations and Caveats

Early termination of the study because of recruitment difficulties lead to insufficient data collection and analysis of primary and secondary outcome measures.

Results Point of Contact

• Title: Dr. Suchita Pakkala
• Organization: Emory University

suchita.pakkala@emoryhealthcare.org

404-686-3496

Study Officials

• Suchita Pakkala, MD

  Emory University/Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: October 17, 2014
• First Posted: October 21, 2014
• Study Start: November 25, 2014
• Primary Completion: January 25, 2021
• Study Completion: January 25, 2021
• Last Updated: April 5, 2022
• Results First Posted: April 5, 2022

Record last verified: 2022-03

Locations

US (3)