PF-07220060 + Fulvestrant for Advanced Breast Cancer
Recruiting in Palo Alto (17 mi)
+244 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Waitlist Available
Sponsor: Pfizer
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?The purpose of this study is to learn about the safety and how effective the study medicine (PF-07220060) plus fulvestrant is compared to the study doctor's choice of treatment in people with advanced or metastatic breast cancer. Advanced cancer is the one that is unlikely to be cured or taken care of with treatment. Metastatic cancer is the one that has spread to other parts of the body.
This study is seeking female and male participants who:
* are 18 years of age or older;
* are hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative;
* have advanced or metastatic breast cancer after taking other treatments before this study;
* have not taken or need to take medications that are not allowed by the study protocol;
* do not have any medical or mental conditions that may increase the risk of study participation.
Half of the participants will take PF-07220060 two times daily by mouth along with fulvestrant. Fulvestrant will be given as a shot into the muscle. The other half will take the study doctor's choice of treatment which can either be:
* Fulvestrant alone taken as shot into the muscle.
* Everolimus along with exemestane taken once daily by mouth.
This study will compare the experiences of participants receiving the study medicine plus fulvestrant to those who are receiving the study doctor's choice of treatment. This will help decide if the study medicine is safe and effective.
Participants will receive study treatment and/or will be in the study until:
* imaging scans (such as an MRI and/or CT) show that their cancer is getting worse.
* the study doctor thinks the participant is no longer benefitting from the study medicine.
* has side effects that become too severe. A side effect is a reaction (expected or unexpected) to a medicine or treatment you take.
* the participant chooses to stop taking part.
Do I have to stop taking my current medications for the trial?
The trial protocol does not specify exactly which medications you must stop, but it mentions that you cannot take certain medications that are not allowed by the study. This includes other anti-cancer therapies, endocrine therapies, growth factors, chronic systemic corticosteroids, and certain inhibitors and inducers. It's best to discuss your current medications with the study doctor to see if they are allowed.
What data supports the idea that PF-07220060 + Fulvestrant for Advanced Breast Cancer is an effective treatment?
The available research shows that a similar drug, palbociclib, when combined with fulvestrant, significantly improved the time patients lived without their cancer getting worse compared to fulvestrant alone. This was observed in multiple studies, including the FLIPPER and PALOMA-3 trials. These studies suggest that combining a drug like PF-07220060 with fulvestrant could also be effective for treating advanced breast cancer.
12345What safety data exists for PF-07220060 + Fulvestrant in advanced breast cancer treatment?
The provided research does not contain specific safety data for PF-07220060 (Atirmociclib) combined with Fulvestrant. Instead, it discusses the safety and efficacy of Palbociclib, another CDK4/6 inhibitor, combined with Fulvestrant. In these studies, neutropenia was the most common adverse event associated with Palbociclib. However, this information may not directly apply to PF-07220060, and specific safety data for PF-07220060 would need to be obtained from studies directly evaluating this treatment combination.
13567Is the drug PF-07220060 (Atirmociclib) combined with Fulvestrant promising for advanced breast cancer?
Yes, combining PF-07220060 with Fulvestrant is promising for advanced breast cancer because Fulvestrant is effective in treating hormone-sensitive breast cancer, especially in postmenopausal women. It works by blocking and breaking down estrogen receptors, which helps slow down cancer growth. Fulvestrant has shown good results when used alone or with other treatments, making it a valuable option in advanced breast cancer care.
89101112Eligibility Criteria
This trial is for adults with HR-positive, HER2-negative advanced or metastatic breast cancer that has worsened after prior treatment. Participants must have a tumor responsive to hormones, provide a tissue sample, and have an ECOG Performance Status of ≤2. They should not be candidates for surgery or radiation with curative intent and must have progressed during or after CDK4/6i treatment.Inclusion Criteria
Measurable disease or non-measurable bone only disease as defined by RECIST version 1.1
I can take care of myself but might not be able to do heavy physical work.
I can provide a sample of my tumor preserved in paraffin.
+4 more
Exclusion Criteria
In visceral crisis at risk of immediately life-threatening complications in the short term
Any medical or psychiatric condition that may increase the risk of study participation or make the participant inappropriate for the study
I do not have active brain metastases or related conditions.
+2 more
Participant Groups
The study compares the effectiveness of PF-07220060 taken orally twice daily combined with fulvestrant injections versus standard treatments chosen by the doctor (fulvestrant alone or everolimus with exemestane). The goal is to determine if PF-07220060 plus fulvestrant is safe and more effective than other options.
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm AExperimental Treatment2 Interventions
PF-07220060 to be taken by mouth as a tablet in combination with fulvestrant (a solution for injection)
Group II: Arm BActive Control3 Interventions
Investigator's choice of therapy of either:
* Fulvestrant alone (a solution for injection), or
* Everolimus in combination with exemestane, both a tablet to be taken by mouth.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Anne Arundel Medical CenterAnnapolis, MD
Keck Medical Center of USC PasadenaPasadena, CA
Hackensack University Medical CenterHackensack, NJ
Memorial Hermann Cancer CenterHouston, TX
More Trial Locations
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Who Is Running the Clinical Trial?
PfizerLead Sponsor
References
Quality of life with palbociclib plus fulvestrant versus placebo plus fulvestrant in postmenopausal women with endocrine-sensitive hormone receptor-positive and HER2-negative advanced breast cancer: patient-reported outcomes from the FLIPPER trial. [2023]In the FLIPPER trial, palbociclib/fulvestrant significantly improved progression-free survival (PFS) compared with placebo/fulvestrant in postmenopausal women with HR+/HER2- advanced breast cancer (ABC).
Randomized phase II study of fulvestrant plus palbociclib or placebo in endocrine-sensitive, hormone receptor-positive/HER2-advanced breast cancer: GEICAM/2014-12 (FLIPPER). [2022]The potential benefit of adding palbociclib to fulvestrant as first-line treatment in hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative endocrine-sensitive advanced breast cancer (ABC) patients remains uncharacterized.
Quality of life with palbociclib plus fulvestrant in previously treated hormone receptor-positive, HER2-negative metastatic breast cancer: patient-reported outcomes from the PALOMA-3 trial. [2022]In the PALOMA-3 study, palbociclib plus fulvestrant demonstrated improved progression-free survival compared with fulvestrant plus placebo in hormone receptor-positive, HER2- endocrine-resistant metastatic breast cancer (MBC). This analysis compared patient-reported outcomes (PROs) between the two treatment groups.
Patterns of treatment and outcome of palbociclib plus endocrine therapy in hormone receptor-positive/HER2 receptor-negative metastatic breast cancer: a real-world multicentre Italian study. [2022]The CDK4/6 inhibitor palbociclib combined with endocrine therapy (ET) has proven to prolong progression-free survival (PFS) in women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). Few data are available regarding the efficacy of such a regimen outside the clinical trials.
Palbociclib: a first-in-class CDK4/CDK6 inhibitor for the treatment of hormone-receptor positive advanced breast cancer. [2022]Palbociclib was approved by the FDA for use in combination with letrozole for the treatment of postmenopausal women with hormone-receptor-positive, HER2-negative advanced breast cancer as initial endocrine-based therapy. In addition, the combination of palbociclib with fulvestrant resulted in superior outcome than fulvestrant alone in those who had progressed during prior endocrine therapy. This research highlight summarized the current development of CDK4/CDK6 inhibitors and future directions in the treatment of advanced hormone-receptor-positive breast cancer.
Palbociclib Plus Fulvestrant in Korean Patients from PALOMA-3 With Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer. [2021]In the PALOMA-3 trial, the median progression-free survival (PFS) was longer among patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) treated with palbociclib plus fulvestrant than those treated with placebo plus fulvestrant. This subgroup analysis examined the efficacy and safety of palbociclib among Korean patients enrolled in PALOMA-3 (n = 43 [palbociclib group, n = 24; placebo group, n = 19]). In both groups, > 40% of patients were pre/perimenopausal at enrollment. The median PFS was significantly prolonged with palbociclib vs. placebo (12.3 [95% confidence interval (CI), 9.1-not estimable] vs. 5.4 months [95% CI, 1.9-9.2]; hazard ratio, 0.40 [95% CI, 0.19-0.83]; one-sided p =0.005), and the confirmed objective response was 21.1% and 11.8%, respectively (odds ratio, 2.0 [95% CI, 0.24-24.8]). Neutropenia was the most common adverse event associated with palbociclib. Overall, palbociclib plus fulvestrant was effective and generally safe among Korean patients with HR+/HER2- ABC, regardless of menopausal status.
Palbociclib Combined with Fulvestrant in Premenopausal Women with Advanced Breast Cancer and Prior Progression on Endocrine Therapy: PALOMA-3 Results. [2022]The efficacy and safety of palbociclib, a cyclin-dependent kinase 4/6 inhibitor, combined with fulvestrant and goserelin was assessed in premenopausal women with advanced breast cancer (ABC) who had progressed on prior endocrine therapy (ET).
Fulvestrant - a new treatment for postmenopausal women with hormone-sensitive advanced breast cancer. [2019]Approximately 75% of breast tumours in postmenopausal women are positive for the oestrogen receptor (ER) and/or the progesterone receptor (PgR) and are, therefore, potential candidates for endocrine treatment. Fulvestrant is a new type of ER antagonist with no agonist effects and a novel mode of action; it binds, blocks and degrades the ER, leading to a reduction in cellular ER and, consequently, in PgR levels. This novel mode of action results in a lack of cross-resistance with other commonly used endocrine treatments. In Phase III trials in postmenopausal women with advanced breast cancer progressing on prior anti-oestrogen therapy, fulvestrant was at least as effective as the third-generation aromatase inhibitor, anastrozole, in terms of time to progression and objective response, and was associated with similar overall survival. In the first-line setting, fulvestrant showed similar efficacy to tamoxifen in patients with ER-positive and/or PgR-positive disease. Efficacy in more heavily pretreated patients has also been demonstrated in the fulvestrant compassionate use programme. Fulvestrant is well tolerated, being associated with a significantly lower incidence of joint disorders compared with anastrozole, and a lower incidence of hot flushes compared with tamoxifen. Fulvestrant, therefore, provides clinicians with a useful additional treatment for hormone-sensitive advanced breast cancer in postmenopausal women. Ongoing trials will help to clarify the optimal position of fulvestrant in the endocrine treatment sequence for these patients.
First-line vs second-line fulvestrant for hormone receptor-positive advanced breast cancer: A post-hoc analysis of the CONFIRM study. [2018]The double-blind, phase III CONFIRM study (NCT00099437) evaluated fulvestrant 500 mg vs fulvestrant 250 mg in postmenopausal women with hormone receptor-positive locally advanced/metastatic breast cancer (LA/MBC). This post-hoc analysis investigated the efficacy and safety of fulvestrant given either first-line or second-line for advanced disease.
Fulvestrant in advanced breast cancer: evidence to date and place in therapy. [2022]Breast cancer is a classical hormone-dependent tumour; therefore, endocrine therapy is the mainstay of treatment for hormone receptor-positive, human epidermal growth factor 2-negative advanced breast cancer. Until recently, classical endocrine agents such as tamoxifen, steroidal and nonsteroidal aromatase inhibitors and fulvestrant have been widely used in postmenopausal patients to treat locally advanced or metastatic disease. However, for patients with this subtype of breast cancer, the landscape of endocrine therapy is rapidly changing. Therapies targeting oestrogen modulation have evolved in recent years following the introduction of targeted agents, mTOR and CDK 4/6 inhibitors that are administered in combination with hormone therapy. As a result, options for endocrine therapy have expanded in recent years, and a variety of single-agent or combinations of targeted drugs and endocrine therapies are accepted. Fulvestrant is a selective oestrogen receptor downregulator (SERD) which was introduced to clinical practice in 2002, initially with the indication to treat postmenopausal women with hormone-receptor-positive advanced breast cancer as second-line therapy postdisease progression after aromatase inhibitors or tamoxifen. Additionally, fulvestrant has also been shown to be active in patients previously untreated with endocrine therapy, either both in the neoadjuvant and the metastatic setting, alone or in combination with other targeted therapies. Currently, the standard dose is 500 mg, which is administered with a loading dose. Fulvestrant received a new FDA indication in December 2016, in combination with palbociclib, both in pre/peri/postmenopausal women with breast cancer progressing after endocrine therapy. This manuscript aims to give an overview of new efficacy data and the current role of fulvestrant in the systemic therapy of hormone-receptor-positive advanced breast cancer, in the context of other available therapeutic modalities.
Efficacy of fulvestrant in the treatment of postmenopausal women with endocrine-resistant advanced breast cancer in routine clinical practice. [2022]This study aimed to describe the efficacy of fulvestrant 500 mg in postmenopausal women with estrogen receptor (ER)-positive advanced/metastatic breast cancer who had disease progression after receiving anti-estrogen therapy in clinical practice, getting real-world data.
Clinical benefit of fulvestrant monotherapy in the multimodal treatment of hormone receptor and HER2 positive advanced breast cancer: a case series. [2020]Fulvestrant is a pure estrogen receptor (ER) antagonist approved for the treatment of metastatic ER positive breast cancer in postmenopausal women with disease progression following antiestrogen therapy. The clinical results of fulvestrant demonstrated encouraging activity in tumors in spite of HER2 positivity, but data about its use after progression on anti-HER2 agents are limited. Partial responses and durations of response of 12, 25, and 38 months in three cases with multiple metastases of ER positive and HER2 positive breast cancer were observed; all patients had been treated with 1-4 regimens of an anti-HER2 agent in combination with chemotherapy or an aromatase inhibitor before the initiation of fulvestrant. Fulvestrant is a valuable option with limited toxicity and durable response in metastatic HER2 and ER positive breast cancer after progression on anti-HER2 agents as well. Therapeutic benefit even in extensive skin metastases and (irradiated) brain metastases may be expected. Further investigations are warranted to establish where it fits into the multimodal management of ER and HER positive breast cancer.