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Tyrosine Kinase Inhibitor

Bosutinib + Palbociclib + Fulvestrant for Advanced Breast Cancer

Phase 1

Waitlist Available

Led By Claudine Isaacs, MD

Research Sponsored by Georgetown University

Eligibility Criteria Checklist

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

Must have

Biopsy proven diagnosis of ER and/or PR positive, HER2 negative, advanced breast cancer (locoregionally recurrent or metastatic disease), either from the primary or a metastatic site.

HER2-negative breast cancer:

Must not have

Patients on chronic anticoagulation (fulvestrant is IM injection)

Presence of a condition that would interfere with enteric absorption of palbociclib/bosutinib.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 1 year

Awards & highlights

No Placebo-Only Group

Summary

This trial is designed to study the safety of a new cancer drug and to see if it works. The drug will be given to patients 5 days a week, with 2 days off, and the dose will be increased gradually to ensure safety. The study will enroll patients in groups of 3, and will observe them for 28 days to see if there are any side effects. If the drug is found to be safe and effective, patients will be able to continue treatment.

Who is the study for?

This trial is for adults over 18 with advanced breast cancer that's ER/PR positive and HER2 negative, who've had no more than three chemo treatments and are resistant to certain inhibitors. Participants must not be pregnant, should agree to contraception if of childbearing potential, have good organ function, and an ECOG status of 0-1 (fully active or restricted in physically strenuous activity but ambulatory).

What is being tested?

The study tests a combination of Bosutinib, Palbociclib, and Fulvestrant on patients with hormone receptor-positive (HR+), HER2-negative advanced breast cancer refractory to CDK4/6 inhibitors. It follows a '3+3' dose escalation design where doses increase until the maximum tolerated dose is found.

What are the potential side effects?

Potential side effects include blood disorders like low neutrophil or platelet counts; liver issues reflected in elevated enzymes; digestive problems affecting absorption; hormonal changes due to fulvestrant injections; fatigue from bosutinib's intensive schedule; plus general risks associated with oral medications.

Eligibility Criteria

Inclusion Criteria

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

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My breast cancer is ER/PR positive and HER2 negative, and it has spread.

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My breast cancer is not HER2 positive.

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I can swallow and keep down pills.

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My breast cancer is hormone receptor-positive.

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I am a woman who has not gone through menopause or has already gone through it.

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I am 18 years old or older.

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My kidney function is within the normal range.

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I am fully active or can carry out light work.

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I've had up to 3 chemotherapy treatments for breast cancer and my cancer did not respond to specific hormone and targeted therapies.

Exclusion Criteria

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

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I am on long-term blood thinners.

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I do not have any conditions that affect how my body absorbs medication.

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I am HIV-positive and on combination antiretroviral therapy.

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I am currently using medications or foods known to strongly affect liver enzymes.

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I do not have any severe illnesses that could interfere with the study.

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I do not have a significant history of liver disease.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 1 year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~1 year

This trial's timeline: 3 weeks for screening, Varies for treatment, and 1 year for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Grade of adverse events of bosutinib when used in combination with palbociclib and fulvestrant in patients with advanced HR+MBC who are refractory to AI and CDK4/6 inhibitors

Incidence of adverse events of bosutinib when used in combination with palbociclib and fulvestrant in patients with advanced HR+MBC who are refractory to AI and CDK4/6 inhibitors

Maximum Tolerated Doses (MTD) of palbociclib and bosutinib when used in combination with fulvestrant in patients with advanced HR+MBC who are refractory to AI and CDK4/6 inhibitors

+2 more

Side effects data

From 2020 Phase 3 trial • 536 Patients • NCT02130557

75%

Diarrhoea

37%

Nausea

36%

Thrombocytopenia

34%

Alanine aminotransferase increased

26%

Aspartate aminotransferase increased

23%

Abdominal pain

23%

Rash

22%

Anaemia

22%

Headache

21%

Vomiting

21%

Fatigue

21%

Lipase increased

18%

Arthralgia

16%

Pyrexia

13%

Constipation

13%

Asthenia

13%

Upper respiratory tract infection

13%

Nasopharyngitis

12%

Neutropenia

12%

Back pain

11%

Decreased appetite

11%

Cough

11%

Dyspnoea

11%

Pruritus

10%

Hypertension

10%

Abdominal pain upper

10%

Dyspepsia

10%

Urinary tract infection

10%

Pain in extremity

Influenza

Amylase increased

Dizziness

Leukopenia

Oedema peripheral

Bronchitis

Blood creatinine increased

Insomnia

Dry skin

Lymphopenia

Influenza like illness

Sinusitis

Blood alkaline phosphatase increased

Blood bilirubin increased

Anxiety

Oropharyngeal pain

Alopecia

Abdominal distension

Toothache

Blood creatine phosphokinase increased

Myalgia

Rash maculo-papular

Gastroenteritis

Muscle spasms

Pneumonia

Gastrooesophageal reflux disease

Face oedema

Weight increased

Hypophosphataemia

Bone pain

Depression

Vision blurred

Hypokalaemia

Night sweats

Cholecystitis acute

Myocardial ischaemia

Atrial fibrillation

Cardiac failure acute

Coronary artery disease

Pericarditis

Hepatitis

Hepatotoxicity

Cellulitis

Femoral neck fracture

Musculoskeletal chest pain

Rectal cancer

Unintended pregnancy

Acute kidney injury

Chronic kidney disease

Haematuria

Pleural effusion

Respiratory failure

Pregnancy of partner

Hypertensive crisis

Periorbital oedema

Eyelid oedema

Conjunctival haemorrhage

Dry eye

100%

80%

60%

40%

20%

Study treatment Arm

Bosutinib

Imatinib

Awards & Highlights

No Placebo-Only Group

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

Trial Design

4Treatment groups

Experimental Treatment

Group I: Dose Level B2Experimental Treatment3 Interventions

* Palbociclib: 100mg daily for 21 days of each 28 day cycle * Bosutinib: 500mg on days 1-5 of each week of the 28 day cycle * Fulvestrant: 500mg on days day 1, 5, and 28 of each 28 day cycle

Group II: Dose Level B1Experimental Treatment3 Interventions

* Palbociclib: 100mg daily for 21 days of each 28 day cycle * Bosutinib: 300mg on days 1-5 of each week of the 28 day cycle * Fulvestrant: 500mg on days day 1, 5, and 28 of each 28 day cycle

Group III: Dose Level A2Experimental Treatment2 Interventions

* Palbociclib: 75mg daily for the first 21 days of each 28 day cycle * Bosutinib: 300mg on days 1-5 of each week of the 28 day cycle

Group IV: Dose Level A1Experimental Treatment3 Interventions

* Palbociclib: 75mg daily for 21 days of each 28 day cycle * Bosutinib: 300mg on days 1-5 of each week of the 28 day cycle * Fulvestrant: 500mg on days day 1, 5, and 28 of each 28 day cycle

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Palbociclib

2017

Completed Phase 3

~3790

Fulvestrant

2011

Completed Phase 3

~4030