Bosutinib + Palbociclib + Fulvestrant for Advanced Breast Cancer

No longer recruiting at 1 trial location
Age: 18+
Sex: Female
Trial Phase: Phase 1
Sponsor: Georgetown University
Must be taking: Aromatase inhibitors, CDK 4/6 inhibitors
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the combination of three drugs—bosutinib, palbociclib, and fulvestrant—to treat advanced breast cancer. The main goal is to determine a safe and effective dose level of these drugs together to see if they can slow or stop disease progression. Women with advanced breast cancer that is estrogen receptor-positive or progesterone receptor-positive, and HER2-negative, who have experienced progression despite previous treatments, might be suitable for this study. Participants will help researchers understand how best to use these medications in treating this type of cancer. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this combination therapy.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop all current medications, but you cannot use drugs that strongly affect CYP3A4, a liver enzyme. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have tested the combination of bosutinib, palbociclib, and fulvestrant for safety. Research shows that this combination undergoes careful study to ensure patient safety. Trials increase doses slowly to manage possible side effects.

Initial findings suggest the treatment is generally well-tolerated. However, side effects like fatigue or nausea can occur. The trial closely monitors these effects and adjusts doses as needed to enhance safety. While this combination remains under study, careful monitoring and dose adjustments aim to ensure participant safety.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Bosutinib, Palbociclib, and Fulvestrant for advanced breast cancer because it targets cancer cells in a unique way. Unlike traditional treatments that might focus solely on hormone receptors or HER2 proteins, this combination uses a multi-faceted approach: Palbociclib inhibits cyclin-dependent kinases 4 and 6, potentially stopping cancer cell division; Bosutinib inhibits multiple tyrosine kinases, disrupting various pathways cancer cells use to grow; and Fulvestrant blocks and degrades estrogen receptors, cutting off a key growth signal. This triple-action strategy could offer a more comprehensive attack on cancer cells, potentially improving outcomes for patients with advanced stages of the disease.

What evidence suggests that this trial's treatments could be effective for advanced breast cancer?

This trial investigates a combination of three drugs—bosutinib, palbociclib, and fulvestrant—to treat advanced breast cancer that is hormone receptor-positive (HR+) and HER2-negative. Participants will receive varying doses of these drugs to assess their effectiveness in halting cancer cell growth. Previous studies have suggested that this combination might help when other treatments fail. Early results appear promising, but further research is necessary to confirm its efficacy. The trial aims to determine if this treatment can control advanced breast cancer when other options have not succeeded.12345

Who Is on the Research Team?

Claudine Isaacs, MD| Cancer Genetics ...

Claudine Isaacs, MD

Principal Investigator

Georgetown University

Are You a Good Fit for This Trial?

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
Cut-off values for positive/negative staining should be in accordance
I am either over 60, had both ovaries removed, haven't had periods for 12 months before treatment, or have menopause-level hormone tests.
See 23 more

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.
See 8 more

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.
How Is the Trial Designed?
4Treatment groups
Experimental Treatment
Group I: Dose Level B2Experimental Treatment3 Interventions
Group II: Dose Level B1Experimental Treatment3 Interventions
Group III: Dose Level A2Experimental Treatment2 Interventions
Group IV: Dose Level A1Experimental Treatment3 Interventions

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

🇺🇸
Approved in United States as Bosulif for:

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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 profile image

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Citations

A phase I trial of palbociclib and bosutinib with fulvestrant ...A phase II trial evaluated the efficacy of bosutinib monotherapy in pretreated patients with advanced breast cancer and found that treatment with bosutinib ...
A phase I trial of palbociclib (palbo) and bosutinib (bos) ...This is an effective combination for HR+/HER2- MBC which warrants further investigation and may represent a mechanism to overcome resistance to CDK4/6i.
Bosutinib, Palbocicilib and Fulvestrant for HR+HER2- ...A Phase I Trial of Palbociclib and Bosutinib With Fulvestrant in Patients With Metastatic Hormone Receptor Positive and HER2 Negative (HR+ HER2-) Breast Cancer ...
4.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/37026029/
A phase I trial of palbociclib and bosutinib with fulvestrant ...This is a phase I, single arm, open-label clinical trial in which we evaluate the combination of palbociclib and fulvestrant with bosutinib in metastatic HR+ ...
Bosutinib + Palbociclib + Fulvestrant for Advanced Breast ...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 ...
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