Bosutinib + Palbociclib + Fulvestrant for Advanced Breast Cancer

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: Georgetown University

Must be taking: Aromatase inhibitors, CDK 4/6 inhibitors

Must not be taking: CYP3A4 inhibitors/inducers, Antiretrovirals

Disqualifiers: Uncontrolled illness, Brain metastases, Liver disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Until disease progression or unacceptable toxicity

19 Participants Needed

Trial Summary

What is the purpose of this trial?

This is an open-label, single-arm, phase I trial. It is designed with a conservative dose escalation plan to ensure patient's safety and with a strong translational component to inform if target inhibition is achieved. With concerns regarding safety, based on extensive available pharmacokinetic data and clinical efficacy experience, bosutinib will be given 5-days in a row followed by 2 days rest in a weekly basis, instead of daily. The protocol will enroll patients per 3+3 escalation design. The Dose Limiting Toxicity (DLT) observation period is 28 days. At the end of DLT observation period of each cohort of 3 patients, decision will be made regarding further escalation or de-escalation according to this plan. Once the MTD of the combination is reached, the safety data will be analyzed. There will be no dose reductions during DLT observation period. Dose reduction within patients (individually) is allowed after the 4-week DLT observation period. Treatment in this phase I trial will be administered until there is disease progression or unacceptable toxicity.

Research Team

Claudine Isaacs, MD

Principal Investigator

Georgetown University

Eligibility Criteria

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).

Inclusion Criteria

AST and/or ALT ≤3 x ULN

I am either over 60, had both ovaries removed, haven't had periods for 12 months before treatment, or have menopause-level hormone tests.

Cut-off values for positive/negative staining should be in accordance

Exclusion Criteria

Pregnant women, or women of childbearing potential without a negative pregnancy test (serum or urine) within 14 days prior to starting treatment on study Breastfeeding must be discontinued prior to study entry.

I am on long-term blood thinners.

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Limiting Toxicity Observation

Observation period to determine dose-limiting toxicities and decide on dose escalation or de-escalation

4 weeks

Weekly visits for monitoring

Treatment

Participants receive Palbociclib, Bosutinib, and Fulvestrant until disease progression or unacceptable toxicity

Until disease progression or unacceptable toxicity

Weekly visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Bosutinib
• Fulvestrant
• Palbociclib

Trial Overview 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.

Participant Groups

Group I: Dose Level B2 Experimental Treatment 3 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 B1 Experimental Treatment 3 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 A2 Experimental Treatment 2 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 A1 Experimental Treatment 3 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

Bosutinib is already approved in United States for the following indications:

Approved in United States as Bosulif for:

• Treatment of adult patients with chronic, accelerated or blast phase Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) with resistance, or intolerance to prior therapy
• Treatment of adult patients with newly-diagnosed chronic phase (CP) Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+CML)
• Treatment of pediatric patients 1 year of age and older with chronic phase (CP) Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+CML), newly-diagnosed or resistant or intolerant to prior therapy

Who Is Running the Clinical Trial?

Georgetown University

Lead Sponsor

Trials

355

Recruited

142,000+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University