← Back to Search

PI3K inhibitor

BYL719 + Letrozole for Breast Cancer

Phase 1

Waitlist Available

Led By Ingrid Mayer

Research Sponsored by Vanderbilt-Ingram Cancer Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Prior radiation castration with amenorrhea for at least 6 months

NOTE: Treatment with a luteinizing hormone-releasing hormone (LH-RH) agonist (such as goserelin acetate or leuprolide acetate) is not permitted for induction of ovarian suppression

Must not have

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

Prior hormonal / endocrine therapy </= 2 weeks prior to study entry. Patients must have recovered from toxicity > grade 1, except for alopecia

Timeline

Screening 3 weeks

Treatment Varies

Follow Up at 6 months of study treatment

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing the side effects and best dose of the PI3K inhibitor BYL719 given with letrozole to treat hormone receptor-positive metastatic breast cancer.

Who is the study for?

This trial is for post-menopausal women with hormone receptor-positive metastatic breast cancer. Participants must have had prior endocrine therapy, be able to swallow pills, and have a life expectancy of at least 6 months. They need proper organ function and no severe heart conditions or uncontrolled illnesses.

What is being tested?

The study is testing the combination of BYL719 (a PI3K inhibitor) and letrozole to see if they are more effective together in stopping tumor growth compared to standard treatments. The trial will also determine the safest doses of BYL719 when used with letrozole.

What are the potential side effects?

Potential side effects include issues related to blocking proteins needed for cell growth which may affect healthy cells as well, leading to fatigue, digestive problems, blood sugar changes, and possible hormonal imbalances.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I have not had a period for at least 6 months due to radiation treatment.

Select...

I am not using hormone therapy to suppress my ovaries.

Select...

My breast cancer is stage IV, ER/PR positive, and HER2 negative.

Select...

I have received hormone therapy for my breast cancer that has spread.

Select...

I have tissue samples from my cancer diagnosis available for study.

Select...

I am fully active or can carry out light work.

Select...

I have had both of my ovaries removed.

Select...

I can swallow and keep down pills.

Select...

I am post-menopausal.

Select...

I am under 55 and have not had a period for 12 months or my hormone levels indicate menopause.

Select...

I am 55 years old or older.

Select...

I am 18 years old or older.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I had radiation therapy more than 2 weeks ago and have recovered from its side effects.

Select...

I stopped hormone therapy over 2 weeks ago and have no major side effects except for hair loss.

Select...

My breast cancer has come back in the same area and can be surgically removed.

Select...

I have a condition that significantly affects my digestion.

Select...

I have diabetes or had gestational diabetes.

Select...

I am not taking medication that affects liver enzyme levels.

Select...

I am on medication that affects my heart's rhythm and cannot change it.

Select...

I have severe heart failure symptoms.

Select...

I do not have serious heart rhythm problems.

Select...

I have a history of abnormal heart rhythms.

Select...

I have a history of chronic liver or kidney failure.

Select...

I am currently on IV antibiotics for an infection.

Select...

I have severe lung problems and need oxygen therapy.

Select...

My blood pressure is controlled and below 180/110 mm Hg.

Select...

My calcium, potassium, or magnesium levels are not normal and can't be corrected.

Select...

I have moderate to severe diarrhea.

Select...

I have a history of pancreatitis.

Select...

My family has a history of long QT syndrome.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ at 6 months of study treatment

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~at 6 months of study treatment

This trial's timeline: 3 weeks for screening, Varies for treatment, and at 6 months of study treatment for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Maximum tolerated dose of BYL719 in combination with letrozole

Secondary study objectives

Clinical benefit rate

Highest tolerated dose of BYL719 in combination with letrozole

Overall progression-free survival

+2 more

Side effects data

From 2017 Phase 1 trial • 17 Patients • NCT02038010

91%

Aspartate Aminotransferase Increased

82%

Hyperglycemia

82%

Peripheral Sensory Neuropathy

73%

Fatigue

73%

Anemia

64%

Hypoalbuminemia

64%

Hypokalemia

64%

Alkaline Phosphatase Increased

55%

Rash Maculo-papular

55%

Cough

55%

Lymphocyte Count Decrease

55%

Platelet Count Decrease

45%

Sinus Tachycardia

45%

Blood Bilirubin Increased

45%

Alanine Aminotransferase Increased

36%

Dry Mouth

36%

Headache

36%

Nausea

36%

Elevated Hemoglobin A1C

27%

Neutrophil Count Decrease

27%

Epistaxis

27%

Diarrhea

27%

Hypocalcemia

27%

Blurred Vision

27%

Urinary Tract Infection

27%

White Blood Cell Decrease

18%

Edema Limbs

18%

Pain

18%

Dizziness

18%

Hypertension

18%

Constipation

18%

Dyspnea

18%

Activated Partial Thromboplastin Time Prolonged

18%

Electrocardiogram QT Corrected Interval Prolonged

18%

Weight Loss

18%

Anorexia

Acute pancreatitis

Radiation Recall Reaction (Dermatologic)

Ear Pain

Hematuria

Pruritus

Bloating

Abdominal Pain

Pancreatitis

Hypoglycemia

Sinus Pain

Chest Wall Pain

Left Ventricular Systolic Dysfunction

Mucositis Oral

Non-Cardiac Chest Pain

Lymphocyte Count Increase

Pneumonitis

Right Bundle Block

Elevated Fasting Plasma

Back Pain

Fever

Palpitations

Ascites

Arthralgia

Bullous Dermatitis

Mucosal Infection

Sinus Bradycardia

Dry Eye

Hypercalcemia

Chills

Hypernatremia

Anxiety

Lymphedema

Insomnia

Gastroesophageal Reflux Disease

Floaters

Urinary Incontinence

Palmar-plantar Erythrodysesthesia Syndrome

Hypoxemia

Alopecia

Hoarseness

Pancreatic Insufficiency

Fractured Rib

Sebaceous Cyst

Post- Menopausal Bleeding

100%

80%

60%

40%

20%

Study treatment Arm

Cohort -1 (250mg BYL719, 3.6mg/kg T-DM1)

Cohort 1 (300mg BYL719, 3.6mg/kg T-DM1)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (PI3K inhibitor BYL719, letrozole)Experimental Treatment4 Interventions

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

PI3K inhibitor BYL719

2014

Completed Phase 1

~20

letrozole

1998

Completed Phase 3

~16660