Phase II Trial of EVEROLIMUS ± Trastuzumab in Hormone-Refractory Metastatic Breast Cancer

NCT00912340 | Completed Phase 2 Results DMC

• 2 other identifiers: IRB00012495WCI1524-08
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 4

Brief Summary

This phase II trial studies how well everolimus with or without trastuzumab works in treating patients with breast cancer that has not responded to hormone therapy and has spread from where it started to other places in the body. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as trastuzumab, may interfere with the ability of tumor cells to grow and spread. Giving everolimus and adding trastuzumab at the time of disease progression may be an effective treatment for breast cancer.

Conditions

Breast Cancer

Keywords

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS) Until First Progression

  Median PFS will be calculated based on time to first progression or death.

  Every 3 to 4 weeks after study start, until progression or death, assessed up to 5 years

Secondary Outcomes (1)

• Progression-free Survival (PFS) in Patients Who Crossed Over

  Every 3 to 4 weeks after study start, until progression or death, assessed up to 5 years

Study Arms (3)

Trastuzumab

EXPERIMENTAL

Patients receive trastuzumab IV over 30 minutes once every 3 weeks and continue to receive their most recent hormone therapy. Patients achieving disease progression receive everolimus PO daily in combination with trastuzumab and hormone therapy.

Biological: Trastuzumab

Everolimus

EXPERIMENTAL

Patients receive everolimus PO daily and continue their most recent hormone therapy. Patients achieving disease progression receive trastuzumab IV over 30-90 minutes once every 3 weeks in combination with everolimus and hormone therapy.

Drug: Everolimus

Trastuzumab and everolimus (ARM REMOVED)

EXPERIMENTAL

Patients receive trastuzumab IV over 30 minutes once every 3 weeks and everolimus PO daily while continuing to receive their most recent hormone therapy.

Drug: Everolimus; Biological: Trastuzumab

Interventions

Everolimus DRUG

Also known as: Afinitor, RAD001

Everolimus; Trastuzumab and everolimus (ARM REMOVED)

Trastuzumab BIOLOGICAL

Also known as: Herceptin

Trastuzumab; Trastuzumab and everolimus (ARM REMOVED)

Eligibility Criteria

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

You may qualify if:

• Patients will be included in the study based on the following criteria:
• Hormone-refractory metastatic breast cancer defined as disease progression within 6 months from starting most recent hormonal therapy
• At least one line of endocrine therapy in the metastatic setting
• Candidate for hormonal therapy (ER and/or progestin receptor \[PR\]-positive at primary diagnosis and at metastatic diagnosis where tissue is available)
• HER2/neu-negative breast cancer by standard criteria (immunohistochemistry \[IHC\] \< 3+ or fluorescence in situ hybridization \[FISH\]-negative if IHC 3+) at primary diagnosis
• Must have a biopsy in the metastatic setting with HER2 expression of 1+ or 2+ by IHC
• If biopsy of metastatic lesion is performed prior to study entry, HER2 expression by IHC must be 1+ or 2+
• Histologically confirmed, measurable or evaluable disease; if disease is measurable, Response Evaluation Criteria In Solid Tumors (RECIST) criteria should be used
• Life expectancy \> 6 months
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Adequate bone marrow function as indicated by the following:
• Absolute neutrophil count (ANC) \> 1500/µL
• Platelets ≥ 100,000/µL
• Hemoglobin \> 10 g/dL
• Adequate renal function, as indicated by creatinine ≤ 1.5x upper limit of normal (ULN)

You may not qualify if:

• Patients will be excluded from the study based on the following criteria:
• Prior treatment with trastuzumab or other HER2-directed therapies or with an mammalian target of rapamycin (mTOR) inhibitor within 12 months of study entry (when cancer was not definitely hormone refractory)
• HER2 0 or 3+ by IHC on pre-treatment biopsy of metastatic lesion (if performed)
• Active infection
• 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
• Ejection fraction \< 50% or below the lower limit of the institutional normal range, whichever is lower
• Hypersensitivity to trial medications
• Emotional limitations
• Prior treatment with any investigational drug within the preceding 4 weeks

Sponsors & Collaborators

• Emory University: lead
• Genentech, Inc.: collaborator
• Novartis Pharmaceuticals: collaborator

Study Sites (4)

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

Location

Emory University Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Robert H. Lurie Comprehensive Cancer Center of Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Everolimus; Trastuzumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Since the initial study design would not allow evaluation of everolimus alone, in 2010, the protocol was amended so that patients were randomized to trastuzumab or everolimus. In 2014, the protocol was amended to close the trastuzumab arm.

Results Point of Contact

• Title: Elisavet Paplomata, Principal Investigator
• Organization: Emory University

elisavet.paplomata@emory.edu

404-778-1900

Study Officials

• Elisavet Paplomata, MD

  Emory University Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: June 2, 2009
• First Posted: June 3, 2009
• Study Start: May 1, 2009
• Primary Completion: July 1, 2017
• Study Completion: July 1, 2017
• Last Updated: December 5, 2018
• Results First Posted: December 5, 2018

Record last verified: 2018-11

Locations

US (4)