BYL719 and Letrozole in Post-Menopausal Patients With Hormone Receptor-Positive Metastatic Breast Cancer

NCT01791478 | Active Not Recruiting Phase 1 DMC

• 2 other identifiers: VICC BRE 12101NCI-2013-00102
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 2

Brief Summary

This phase I trial studies the side effects and best dose of the PI3K inhibitor BYL719 when given together with letrozole in treating patients with hormone receptor-positive metastatic breast cancer. The PI3K inhibitor BYL719 may stop the growth of tumor cells by blocking some of the proteins needed for cell growth. Hormone therapy using letrozole may fight breast cancer by blocking the use of estrogen by the tumor cells. Giving the PI3K inhibitor BYL719 together with letrozole may kill more tumor cells

Conditions

Estrogen Receptor-positive Breast Cancer; HER2-negative Breast Cancer; Invasive Ductal Breast Carcinoma; Progesterone Receptor-positive Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer

Keywords

-Metastatic breast cancer, PI3K inhibitor, Endocrine therapy

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose of BYL719 in combination with letrozole

  Highest dose of BYL719 tested in which a DLT is experienced by 0 out of 3 or 1 of 6 patients, based on the NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0

  4 weeks

Secondary Outcomes (5)

• Highest tolerated dose of BYL719 in combination with letrozole

  8 weeks

• Clinical benefit rate

  At 6 months of study treatment

• Overall progression-free survival

  Up to 4 weeks after interruption of study treatment

• Overall response

  Every 8 weeks to interruption of treatment

• Worst grade toxicities

  Up to 4 weeks after interruption of study treatment

Study Arms (1)

Treatment (PI3K inhibitor BYL719, letrozole)

EXPERIMENTAL

Patients receive PI3K inhibitor BYL719 PO QD and letrozole PO QD. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Drug: PI3K inhibitor BYL719; Drug: letrozole; Other: laboratory biomarker analysis; Other: pharmacological studies

Interventions

PI3K inhibitor BYL719 DRUG

Given PO

Also known as: BYL719, a-specific phosphoinositide 3-kinase inhibitor BYL719

Treatment (PI3K inhibitor BYL719, letrozole)

letrozole DRUG

Given PO

Also known as: 112809-51-5, 4,4'-(1H-1,2,4triazol-1-ylmethylene)dibenzonitrile, 719345, CGS 20267,, Femara,LTZ

Treatment (PI3K inhibitor BYL719, letrozole)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (PI3K inhibitor BYL719, letrozole)

pharmacological studies OTHER

Correlative studies

Treatment (PI3K inhibitor BYL719, letrozole)

Eligibility Criteria

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

You may qualify if:

• Patients must provide informed written consent.
• Patients must be \>/= 18 years of age.
• ECOG performance status 0 - 1.
• Clinical stage IV invasive mammary carcinoma, ER-positive and/or PR-positive by immunohistochemistry (IHC) and HER2 negative (by IHC or ISH). Patients may have either measurable or non-measurable disease, both are allowed.
• A minimum of 10 patients in the trial (\~50%) will need to have a PIK3CA mutation in their cancer
• Patients must have had at least one line of endocrine therapy in the metastatic setting, or be diagnosed with metastatic breast cancer during or within 1 year of adjuvant endocrine therapy. There is no limit on lines of prior treatment in the metastatic setting.
• Patients must have available tissue (archived formalin-fixed paraffin embedded blocks (FFPB) or fresh frozen tissue from original diagnosis or metastatic setting) for correlative studies. Tissue needs to be located and available at the time of registration (tissue needs to be submitted within 3 weeks of study initiation). Patients will not be able to start study drugs without tissue availability.
• Life expectancy ≥ 6 months
• Patients must have adequate hematologic, hepatic, and renal function. All laboratory tests must be obtained less than 1 week from study entry. This includes:
• ANC \>/= 1,500/mm3
• platelet count \>/=100,000/mm3
• HgB ≥ 9 g/dL
• Creatinine ≤ 1.5x ULN
• INR ≤ 2
• Fasting plasma glucose ≤ 140 mg/dL

You may not qualify if:

• Locally recurrent resectable breast cancer.
• Any kind of malabsorption syndrome significantly affecting gastrointestinal function.
• Patients with clinically manifest diabetes mellitus (treated and/or clinical signs or with fasting glucose \>/= 140 mg/dL / 7.8 mmol/L), history of gestational diabetes mellitus or documented steroid-induced diabetes mellitus.
• Patients who have received radiation therapy \</= 2 weeks prior to study entry. Patients who have received prior radiotherapy must have recovered from toxicity (≤ grade 1) induced by this treatment.
• Patients who have received systemic anti-cancer therapy such as chemotherapy, immunotherapy and/or biologic therapy \</= 4 weeks prior to study entry. Concurrent anti-cancer therapy (chemotherapy, immunotherapy, biologic therapy) other than the ones specified in the protocol is not permitted during study participation. Patients must have discontinued the above cancer therapies for 4 weeks prior to the first dose of study medication, as well as recovered from toxicity (to ≤ than grade 1, except for alopecia) induced by previous treatments. Any investigational drugs should be discontinued 4 weeks prior to the first dose of study medication.
• Prior hormonal / endocrine therapy \</= 2 weeks prior to study entry. Patients must have recovered from toxicity \> grade 1, except for alopecia.
• Prior therapy with a PI3K inhibitor. Prior use of Akt or mTOR inhibitors are allowed.
• Patients who have received herbal medications \</= 2 weeks prior to study entry. Herbal medications include, but are not limited to: St. John's wort, Kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng.
• Use of drugs that are CYP3A4 modifiers
• Patients who are currently receiving medication with a known risk of prolonging the QT interval or inducing Torsades de Pointes (TdP) and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug treatment.
• Patients with a family history of congenital long QT syndrome
• Patients with abnormal calcium, potassium, or magnesium levels that cannot be adequately corrected to within normal range prior to initiation of study drugs
• Uncontrolled intercurrent illness including, but not limited to:
• ongoing or active infection requiring parenteral antibiotics
• impairment of lung function (COPD \> grade 2, lung conditions requiring oxygen therapy)

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Massachusetts General Hospital, Dana-Farber Cancer Institute

Boston, Massachusetts, 02114, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232-6838, United States

Location

Related Links

• Vanderbilt-Ingram Cancer Center, Find a Clinical Trial

MeSH Terms

Conditions

Carcinoma, Ductal, Breast; Breast Neoplasms

Interventions

Alpelisib; Letrozole

Condition Hierarchy (Ancestors)

Carcinoma, Ductal; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Ductal, Lobular, and Medullary; Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Ingrid Mayer

  Vanderbilt-Ingram Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: February 11, 2013
• First Posted: February 15, 2013
• Study Start: April 1, 2013
• Primary Completion: December 1, 2014
• Study Completion: February 28, 2025
• Last Updated: July 23, 2024

Record last verified: 2024-07

Locations

US (2)