Palbociclib plus fulvestrant in women with hormone receptor positive and human epidermal growth factor receptor type 2 negative locally advanced or metastatic breast cancer previously treated with a CDK4/6 inhibitor in combination with hormonal therapy: a multicenter, phase II trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Consorzio Oncotech, Consorzio Oncotech

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

18 Oct 2019 → ongoing

Decision date (initial)

2024-05-29

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

Pfizer S.r.l.

External identifiers

EU CT number

2024-513372-18-00

EudraCT number

2019-000221-45

ClinicalTrials.gov

NCT04318223

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

The aim of the present study is to evaluate the efficacy and safety of palbociclib plus fulvestrant after failure of a combined treatment of hormonal therapy (aromatase inhibitor or tamoxifen ± LHRHa) plus a CDK4/6 inhibitor, in women with HR+ and HER2-LABC or MBC

Secondary objectives 1

1. To assess predictive biomarkers of response/resistance to fulvestrant plus palbociclib using metastatic tumor tissue samples and liquid biopsies

Conditions and MedDRA coding

Pre- and post-menopausal women with HR+/HER2- LABC or MBC whose disease has progressed to CDK4/6 inhibitor in combination with a hormonal therapy in the adjuvant or metastatic setting

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Adult (>=18 years of age) pre or post-menopausal women with LABC or MBC not amenable to curative treatment by surgery or radiotherapy, progressing to a CDK4/6 inhibitor in combination with aromatase inhibitor or tamoxifen in the adjuvant or metastatic setting. To be enrolled in the present trial patients must have relapsed at least after 12 months from the last CDK4/6 dosage in the adjuvant setting or at progression from a first line combined hormonal treatment for metastatic disease with a CDK4/6 inhibitor plus AI or Tam with duration of, at least, 6 months. For metastatic disease, patients must have achieved, at least a stable disease while the first line hormonal treatment with a CDK4/6 inhibitor plus AI or Tam to be enrolled in the trial.
2. Patients receiving up to one line of chemotherapy before the first line hormonal treatment with a CDK4/6 inhibitor for metastatic disease may be enrolled in the study.
3. Histological confirmation of ER and/or PgR >= 1% and HER2 negative breast cancer (IHC status 0, 1+, 2+ and FISH not amplified).
4. Premenopausal women: in order to be eligible must have achieved surgical menopause with bilateral oophorectomy or ovarian radiation or medical menopause by treatment with a luteinizing hormone-releasing hormone (LHRH) agonist (LHRHa) for induction of ovarian suppression.
5. Radiological or objective evidence of recurrence or progression on or after the last systemic therapy prior to enrollment
6. Patients who received <= 28 days of fulvestrant for second line advanced breast cancer treatment prior to study enrollment are eligible.
7. Patients must have: - At least one lesion that can be accurately measured in at least one dimension >= 20 mm with conventional imaging techniques or >= 10 mm with spiral CT or MRI - Bone lesions: lytic or mixed (lytic + sclerotic) in the absence of measurable disease as defined above.
8. Adequate bone marrow and coagulation and adequate organ function defined as follows: - ANC > 1,000/mm3 (1.0 x 109/L); - Platelets > 75,000/mm3 (75 x 109/L); - Hemoglobin >= 9 g/dL (90 g/L); - Serum creatinine <= 1.5 x ULN or estimated creatinine clearance >= 60 ml/min as calculated using the method standard for the institution; - Total serum bilirubin <= 1.5 x ULN (<2.5 ULN if Gilbert’s disease); - AST and/or ALT <= 3 x ULN (<= 5 x ULN if liver metastases present); - Alkaline phosphatase <= 2.5 x ULN (<= 5 x ULN if bone or liver metastases present); - ECOG Performance Status <= 2; - Resolution of all acute toxic effects of prior therapy or surgical procedures to National Cancer Institute (NCI) CTCAE Grade <=1 (except alopecia).
9. Estimated life expectancy > of 12 weeks.
10. Patients must perform liquid biopsy at study entry and at disease progression. Tissue biopsy of the most accessible metastatic site at study entry and at disease progression are required but not mandatory.
11. Written informed consent obtained before any screening procedure and according to local guidelines.

Exclusion criteria 23

1. HER2-overexpressing patients by local laboratory testing (IHC3+ staining or in situ hybridization positive).
2. Patients who received > 1 line of chemotherapy as treatment for MBC.
3. Patients who received > 1 line of a CDK4/6 inhibitor in combination with hormonal treatment for LABC or MBC or who have relapsed at less than 12 months from the end of adjuvant treatment with a CDK4/6 inhibitor. For metastatic disease, patients with a progressive disease within the first 6 months of treatment while on first line therapy with a CDK4/6 inhibitor, will be excluded.
4. Patients receiving chemotherapy or any type of hormonal therapy after treatment with a CDK4/6 inhibitor for metastatic disease.
5. Patients interrupting the previous treatment with CDK4/6 inhibitor for cardiac and/or hepatic toxicity and not for disease progression.
6. Pregnant, lactating women.
7. Known hypersensitivity to CDK4/6 inhibitors, fulvestrant, or to any of the excipients.
8. Radiotherapy within four weeks prior to enrollment (baseline/treatment start) except in case of localized radiotherapy for analgesic purpose or for lytic lesions at risk of fracture which can then be completed within two weeks prior to enrollment (baseline/treatment start). Patients must have recovered from radiotherapy toxicities prior to enrollment.
9. Currently receiving hormone replacement therapy, unless discontinued prior to enrollment.
10. Patients receiving concomitant immunosuppressive agents or chronic corticosteroids use, at the time of study entry except in cases outlined below: a. short duration (<2 weeks) of systemic corticosteroids is allowed (e.g., chronic obstructive pulmonary disease, anti-emetic); b. low doses of corticosteroids for brain metastasis treatment is allowed.
11. Patients with symptomatic visceral disease in need of urgent disease control (e.g., significant dyspnea related to pulmonary lymphangitic carcinomatosis and lung metastases or clinically meaningful symptomatic liver metastasis at the judgement of treating investigator).
12. Symptomatic brain metastases.
13. Patients with a known history of HIV seropositivity.
14. Active, bleeding diathesis, or on oral anti-vitamin K medication (except low dose warfarin, low-molecular-weight heparin (LMWH) and acetylsalicylic acid or equivalent, as long as the INR is <= 2.0).
15. Any severe and/or uncontrolled medical conditions such as: unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction <= 6 months prior to enrollment, serious uncontrolled cardiac arrhythmia.
16. Acute and chronic, active infectious disorders.
17. Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of the study treatments (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome).
18. Inability to swallow oral medications.
19. Significant symptomatic deterioration of lung function.
20. Patients being treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A (Rifabutin, Rifampicin, Clarithromycin, Ketoconazole, Itroconazole, Voriconazole, Ritinavir, Telithromycin) within the last 5 days prior to enrollment.
21. History of non-compliance to medical regimens.
22. Patients refusing to perform liquid biopsy at study entry and disease progression.
23. Patients unwilling to or unable to comply with the protocol.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To evaluate the efficacy of the combination of fulvestrant plus palbociclib at the progression of a combined treatment of hormonal therapy (aromatase inhibitor or tamoxifen ± LHRHa) and CDK4/6 inhibitors with respect to: • Overall response rate (ORR) • Progression Free Survival (PFS) • 6-month PFS rate • Overall Survival (OS) • Safety and tolerability

Secondary endpoints 1

1. To assess predictive biomarkers of response/resistance to fulvestrant plus palbociclib using metastatic tumor tissue samples and liquid biopsies.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Consorzio Oncotech

Sponsor organisation

Consorzio Oncotech

Address

Via Sergio Pansini 5

City

Naples

Postcode

80131

Country

Italy

Scientific contact point

Organisation

Consorzio Oncotech

Contact name

Sabino De Placido

Public contact point

Organisation

Consorzio Oncotech

Contact name

Sabino De Placido

Consorzio Oncotech

Sponsor organisation

Consorzio Oncotech

Address

Via Sergio Pansini 5

City

Naples

Postcode

80131

Country

Italy

Scientific contact point

Organisation

Consorzio Oncotech

Contact name

Sabino De Placido

Public contact point

Organisation

Consorzio Oncotech

Contact name

Sabino De Placido

Locations

1 EU/EEA country · 26 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

1 submissions — initial application plus substantial / non-substantial modifications