What is palbociclib plus fulvestrant studying for ER positive HER2 negative breast cancer?

This trial studies whether palbociclib combined with fulvestrant can delay or prevent relapse in patients with ER positive, HER2 negative breast cancer who show early signs of relapse through circulating tumour DNA detection. Researchers aim to improve outcomes by treating patients identified as high risk before visible cancer returns.

Who may be eligible for this breast cancer clinical trial?

Adults aged 18 years or older with ER positive, HER2 negative breast cancer who are receiving standard endocrine therapy and have high-risk features may qualify. Both men and women can participate. Patients should have no visible metastatic disease and meet specific health requirements. Please review eligibility criteria for more details.

Is there any cost to participate in this breast cancer clinical trial?

Study-related care, including the study drugs and all trial visits, is provided at no cost. However, personal travel and other expenses may vary and are not guaranteed to be covered.

Actively Recruiting

Phase 2

Age: 18Years +

All Genders

ID04985266

Early Detection of Molecular Relapse Using Circulating Tumour DNA and Treatment with Palbociclib Plus Fulvestrant Compared to Standard Endocrine Therapy in Adults with ER Positive HER2 Negative Breast Cancer

Led by Royal Marsden NHS Foundation Trust · Updated on 2024-12-05

1100

Participants Needed

Research Sites

156 weeks

Total Duration

AI-Summary

What this Trial Is About

Researchers are evaluating the use of circulating tumour DNA ctDNA analysis to detect early molecular relapse in patients with estrogen receptor positive ER and HER2 negative breast cancer who are undergoing adjuvant endocrine therapy. This trial aims to determine if treatment with palbociclib plus fulvestrant can delay or prevent relapse in patients who show positive ctDNA results. The study is a Phase 2, multi-centre, randomized, open-label trial focusing on high-risk patients with early-stage breast cancer. The trial has two main phases a surveillance phase and a treatment phase. During the surveillance phase, patients receive ctDNA testing every three months for up to three years to monitor for molecular relapse. If ctDNA is detected without visible disease on imaging, patients enter the treatment phase, where they are randomly assigned to receive either standard endocrine therapy or a combination of palbociclib and fulvestrant for up to 24 months. Palbociclib is taken orally daily for 21 days of each 28-day cycle, while fulvestrant is given as intramuscular injections on specific days of each cycle. Imaging is performed every six months to check for overt disease. Participants undergo regular blood tests for ctDNA monitoring during the surveillance phase and receive clinical assessments, imaging scans, and quality of life questionnaires during the treatment phase. Researchers measure the incidence of positive ctDNA results, relapse-free survival, and monitor adverse events. The total follow-up for relapse-free survival extends up to 60 months from randomization, while safety and quality of life are assessed up to 24 months. If macroscopic disease appears, participants stop trial treatment and receive standard care outside the study.

CONDITIONS

Brief Title

A Trial of Early Detection of Molecular Relapse With Circulating Tumour DNA Tracking and Treatment With Palbociclib Plus Fulvestrant Versus Standard Endocrine Therapy in Patients With ER Positive HER2 Negative Breast Cancer

Who Can Participate

Age: 18Years +

All Genders

Eligibility Criteria

You may qualify if you...

Provide written informed consent for the trial and sample donation
Male or female patients aged 18 years or older
ECOG performance status of 0, 1, or 2
Histologically confirmed primary ER positive (Allred score 6/8 or greater or 10% cancer cells) and HER2 negative breast cancer
High-risk early stage breast cancer based on lymph node involvement, tumour size, histological grade, or genomic risk scores
Available archival tumour tissue sample
No evidence of visible distant metastatic or incurable locally advanced disease on imaging
Receiving standard endocrine therapy for at least 6 months and up to 7 years, with at least 3 more years planned
Surgery with clear margins completed
Willing to use adequate contraception if of reproductive potential during treatment and follow-up
Willing to have frequent blood tests
Signed informed consent for treatment phase
Women of childbearing potential must have a negative pregnancy test before randomisation
Adequate bone marrow and organ function by laboratory tests
Post-menopausal or pre/peri-menopausal with ovarian suppression if receiving palbociclib plus fulvestrant

You will not qualify if you...

Receiving or planning treatments other than endocrine therapy or bisphosphonates for breast cancer
Prior CDK4/6 inhibitor treatment within the past 12 months
Previous therapeutic dose of fulvestrant
Other cancer diagnosis within past 5 years except certain skin or cervical cancers
Participation in therapeutic trials with continued experimental therapy post-surgery
Treatment with experimental products within 4 weeks prior to trial
Unresolved side effects from prior cancer therapies beyond grade 1 (except alopecia)
Significant gastrointestinal conditions affecting oral medication absorption
Severe uncontrolled medical conditions or safety risks per investigator
Uncontrolled heart disease including recent heart attack, heart failure, arrhythmia, or long QT syndrome
History of pneumonitis, interstitial lung disease, or pulmonary fibrosis
Known HIV or active Hepatitis B or C infection
Pregnancy or breastfeeding
History of bleeding disorders or anticoagulant treatments (except some allowed medications)
Severe liver or kidney impairment
Bilateral or multifocal tumours not deemed a single primary cancer
Hypersensitivity to palbociclib plus fulvestrant components
Major surgery within 4 weeks before treatment or incomplete recovery
Current use of warfarin or similar anticoagulants
Use of medications or supplements affecting CYP3A4 that cannot be stopped before treatment
History of non-compliance with medical regimens

Your Study Journey

Screening

Duration - 2 to 4 weeks

Participants are screened for eligibility to participate in the trial.

1 visit (in-person)

Surveillance

Duration - Up to 3 years

Participants receive ctDNA testing every three months to monitor for molecular relapse while receiving standard endocrine therapy and have no visible disease on imaging.

Quarterly visits for ctDNA testing and imaging as needed

Treatment

Duration - Up to 24 months

Participants with positive ctDNA but no visible disease are randomized to receive either palbociclib plus fulvestrant or standard endocrine therapy for up to 24 months, with imaging every six months to check for macroscopic disease.

Monthly visits for medication administration and assessments; imaging every 6 months