A Phase III Open-label, Multicenter, Randomized Trial of Adjuvant Palbociclib in Combination With Endocrine Therapy Versus Endocrine Therapy Alone for Patients With Hormone Receptor Positive / HER2-negative Resected Isolated Locoregional Recurrence of Breast Cancer

Plain English Summary

Palbociclib for HR Positive / HER2-negative Isolated Locoregional Recurrence of Breast Cancer is a Phase 3 clinical trial sponsored by ETOP IBCSG Partners Foundation studying Breast Cancer Recurrent. Tests a new combination of drugs to see if it works better than standard treatment for breast cancer that has come back in the same area after surgery. For patients with hormone receptor positive / HER2-negative breast cancer that has come back in the same area after surgery. Participation involves taking a new drug called palbociclib along with standard hormone therapy for 3 years. Alternative treatments include standard hormone therapy alone. The trial aims to enroll 405 participants.

Official Summary

POLAR is a phase III clinical trial, which will test the safety and efficacy of an investigational combination of drugs to learn whether the combination of drugs works for a specific cancer. Palbociclib (Ibrance®) is the name of the investigational agent, which is assessed together with standard anti-hormone therapy in this study. Palbociclib is used to treat patients with hormone receptor-positive / HER2-negative breast cancer which has spread beyond the original tumor and/or to other organs. During this study, anti-hormone therapy will consist of either a selective estrogen receptor modulator (such as tamoxifen) or an aromatase inhibitor (anastrozole, letrozole, exemestane) or fulvestrant (Faslodex®). Premenopausal women and men may also receive a drug called an LHRH (luteinizing hormone-releasing hormone) agonist by injection. It is standard of care for people with hormone receptor positive breast cancer to take anti-hormone therapy. The study doctor will determine the type of standard anti-hormone therapy that will be given during this trial. The purpose of the POLAR study is to compare the effect of using 3 years of palbociclib in combination with standard anti-hormone therapy with standard anti-hormone therapy alone and to evaluate the time until the breast cancer returns, if it does return.

Who Can Participate

Here is what you need to know about eligibility for this trial. Eligible if you have hormone receptor positive / HER2-negative breast cancer that has come back in the same area after surgery. Not eligible if the cancer has spread to other parts of the body or if you have taken palbociclib before. Must be 18 years or older and in good health. Women must not be pregnant or breastfeeding. This trial is studying Breast Cancer Recurrent, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures how long the cancer stays away after treatment, which is important for patients to know how well the treatment works. The specific primary outcome measures are: Duration of invasive disease free survival of all randomized participants. (Assessed from the date treatment starts until the date of first documented invasive local, regional or distant recurrence, a second invasive cancer or death, or until approximately 4 years after treatment stops.). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial is important because it aims to find a better way to treat breast cancer that has come back in the same area after surgery. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Breast Cancer Recurrent, where improved treatment options are needed.

Investor Insight

The market for breast cancer treatments is large, and this trial could bring a new effective treatment to market, potentially improving patient outcomes. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage.

Is This Trial Right for Me?

Ask your doctor if you are a good candidate for this trial. You will take a new drug called palbociclib and standard hormone therapy for 3 years. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 405 participants

Interventions

• DRUG: Palbociclib 125mg — Palbociclib 125 mg oral tablet taken daily for 3 years from randomization
• DRUG: Standard endocrine therapy — Aromatase inhibitor (anastrozole or exemestane or letrozole) oral daily tablet, or Selective Estrogen Receptor Modulator (SERM) such as tamoxifen oral daily tablet or fulvestrant (Faslodex) injection once every 2 weeks for 3 doses then every month. Premenopausal women and men may also receive an LHRH (luteinizing hormone-releasing hormone) agonist by injection. Standard endocrine therapy will be given for at least 3 years from randomization.

Primary Outcomes

• Duration of invasive disease free survival of all randomized participants. (Assessed from the date treatment starts until the date of first documented invasive local, regional or distant recurrence, a second invasive cancer or death, or until approximately 4 years after treatment stops.)

Secondary Outcomes

• Number of participants with treatment related adverse events. (Adverse events will be collected from the date consent is signed, and during treatment until 30-60 days after treatment stops.)
• Duration of breast cancer free interval of all randomized participants. (Assessed from the date of randomization until the date of first documented breast cancer recurrence, or until approximately 4 years after treatment stops.)
• Duration of distant recurrence free interval of all randomized participants. (Assessed from the date of randomization until the date of first documented distant disease progression, or until approximately 4 years after treatment stops.)
• Duration of overall survival of all randomized participants. (Assessed from the date of randomization until approximately 4 years after treatment stops, or until the date of death from any cause.)

Full Eligibility Criteria

Inclusion Criteria:

1. Histologically confirmed invasive breast cancer, defined as first proven ipsilateral local and/or regional recurrence of a primary invasive breast cancer in at least one of these sites:

   * breast;
   * the chest wall including mastectomy scar and/or skin;
   * axillary or internal mammary lymph nodes.
2. Completion of locoregional therapy:

   * completion of gross excision of recurrence within 6 months prior to randomization;
   * completion of radiotherapy (if given) more than 2 weeks prior to randomization
3. Negative or microscopically involved margins
4. Female or male aged 18 years or older
5. ECOG performance status 0 or 1
6. Recurrent tumor must be hormone receptor positive: ER+ and/or PgR+ ≥1% by IHC
7. Recurrent tumor must be HER2-negative (0, 1+, 2+ by IHC and/or ISH/FISH not amplified).Tumor with HER2 status 2+ by IHC must also be negative (not amplified) by ISH/FISH

8.-10. Normal hematological, renal, and liver function 11. The patient agrees to make tumor (diagnostic core biopsy or surgical specimen of ipsilateral isolated locoregional recurrence) available for submission for central pathology review 12. Patients must either be planned to initiate, or have already started, endocrine therapy for ipsilateral isolated locoregional recurrence 13.) Written Informed Consent prior to randomization

Exclusion Criteria:

1. Recurrence of any size with direct extension to the chest wall and/or to the skin (ulceration or skin nodules) not surgically removable
2. Evidence of distant metastasis as based on conventional staging examinations (physical, chest X-ray or CT, abdominal ultrasound or CT, bone scintigraphy or FDG-PET-CT).
3. Bilateral synchronous or metachronous invasive breast cancer (in situ carcinoma of the contralateral breast is allowed)
4. Inflammatory breast cancer
5. Patients with a history of malignancy, other than invasive breast cancer, with the following exceptions:

   * Patients diagnosed, treated and disease-free for at least 5 years and deemed by the investigator to be at low risk for recurrence of that malignancy are eligible.
   * Patients with the following malignancies are eligible, even if diagnosed and treated within the past 5 years: ductal carcinoma in situ of the breast; cervical cancer in situ; thyroid cancer in situ; non-metastatic, non-melanomatous skin cancers.
6. Previous treatment with palbociclib or any other CDK 4/6 inhibitors
7. Previous or planned chemotherapy or planned radiotherapy for the ipsilateral isolated locoregional recurrence (radiotherapy is allowed, but must be completed more than 2 weeks prior to randomization)
8. Concurrent disease or condition that would make the patient inappropriate for study participation or any serious medical disorder that would interfere with the patient's safety
9. Pregnant or lactating women; lactation has to stop before randomization
10. Patients with psychiatric illness/social situations that would limit compliance with study requirements
11. Contraindications or known hypersensitivity to the palbociclib or excipients
12. History of extensive disseminated/bilateral or known presence of interstitial fibrosis or interstitial lung disease, including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, obliterative bronchiolitis, and pulmonary fibrosis. A history of prior radiation pneumonitis is not considered an exclusion criterion.

Trial Locations

• Medizinische Universität Graz (MUG), Graz, Austria
• Medizinische Universität Innsbruck - Univ.-Klinik f. Frauenheilkunde, Innsbruck, Austria
• Uniklinikum Salzburg, Salzburg, Austria
• MUW - Universitätsklinik für Innere Medizin, Vienna, Austria
• Institut Sainte Catherine, Avignon, France
• Institut Bergonie, Bordeaux, France
• Polyclinique Bordeaux Nord, Bordeaux, France
• Centre Francois Baclesse, Caen, France
• Cêntre Hospitaler de Cholet, Cholet, France
• Centre Georges François Leclerc, Dijon, France
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Breast cancer, HER2-negative breast cancer, hormone receptor positive breast cancer, breast cancer recurrence, breast cancer treatment

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