Phase 3 Trial of Fuvestrant(Faslodex®)in women with Breast Cancer

• Research type

  Research Study

• Full title

  Multicentre, Randomised, Double-Blind, Placebo Controlled, Phase 3 Trial of Fulvestrant (Faslodex®) With or Without PD-0332991 (Palbociclib) ± Goserelin in Women with Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer Whose Disease Progressed After Prior Endocrine Therapy.

• IRAS ID

  141540

• Contact name

  Nicola Turvey

• Contact email

  nicola.turvey@parexel.com

• Sponsor organisation

  Pfizer Inc

• Eudract number

  2013-002580-26

• Clinicaltrials.gov Identifier

  NCT01942135

• Duration of Study in the UK

  3 years, 0 months, 14 days

• Research summary

  Summary of Research
  Breast cancer is a type of cancer arising from the breast tissue which accounts for over 20% of all cancers in women. Hormone receptor positive (HR+)/Hormone Growth factor receptor 2-negative (HER2-negative) breast cancer is the most common type. Receptors are proteins in cells which attract chemicals to bring about certain changes in the cells whereas growth factors are chemicals which are attracted to the receptors. HER2 is a protein found on the surface of cancer cells and HR+ cancer have more receptors than other cancer cells.

  Patients diagnosed with breast cancer are usually diagnosed early and are treated with a course of endocrine therapy (hormone therapy). About one third of all HR+/HER2-negative patients diagnosed experience disease reoccurrence; this is due to the endocrine therapy being only partially effective and can lead to resistance to the therapy so the management of relapsed cancer is difficult. Fluvestrant is a current treatment for breast cancer for women with disease progression following hormone therapy.

  Palboiciclib is an orally-active growth factor inhibitor currently being developed to treat breast cancer. In early clinical trials palbociclib has shown to inhibit the cells from multiplying with an increase in progression free survival (longer between reoccurrence of cancer).

  Pfizer is sponsoring a study to collect information about whether Fluvestrant would be more or less effective if used in combination with palboicilib in prolonging progression free survival.

  This is a randomised, placebo-controlled, double-bind study meaning neither the participant nor the study doctor will know whether they will be receiving the medication or the placebo (drug with no medical effect). The participant will receive either Fluvestrant and palboicilib or Fluvestrant and placebo.

  This is a multicentre study which will take place across approximately 20 countries worldwide. It is anticipated that over 400 women will be enrolled.

  Summary of Results
  The following study has now ended: Multicentre, Randomised, Double-Blind, Placebo-Controlled, Phase 3 Trial Of Fulvestrant (Faslodex®) With Or Without Pd-0332991 (Palbociclib) +/- Goserelin In Women With Hormone Receptor-Positive, Her2-Negative Metastatic Breast Cancer Whose Disease Progressed After Prior Endocrine Therapy.

  Who carried out the research?
  This study was conducted and funded by Pfizer, Inc.

  What public involvement there was in the study?
  This study did not involve the public in its development or organisation, due to the complexity and advanced scientific nature of the study design. The public were involved only as study participants.

  Where and when the study took place
  This study took placed in USA, Canada, Australia, Belgium, Italy, Netherlands, Portugal, Romania, Russia, Ukraine, Taiwan, Korea, Germany, Japan, UK , Irelands, Turkey. Participants were recruited between 26-Sep-2013 and 30-Jul-2014. The study was completed 28 September 2022.

  Why was the research needed?
  This study was conducted due to the need for more effective treatments for breast cancer following disease progression. Patients diagnosed with breast cancer are usually diagnosed early and are treated with a course of endocrine therapy (hormone therapy). About one third of all HR+/HER2­negative patients diagnosed experience disease reoccurrence; this is due to the endocrine therapy being only partially effective and can lead to resistance to the therapy, so the management of relapsed cancer is difficult. Fulvestrant is a current treatment for breast cancer for women with disease progression following hormone therapy.

  What were the main questions studied?
  The purpose of this study was to compare the effects of the study drug, PD-0332991 (also called “palbociclib”) in combination with fulvestrant (Faslodex®) with a placebo in combination with fulvestrant to find out which study treatment is better at treating cancer and preventing disease progression.

  Who participated in the study?
  711 individuals participated in this study. These individuals were mostly white, postmenopausal women, with a documented sensitivity to prior hormonal therapy. Over half of which had visceral metastases (soft tissue lesions).

  What treatments or interventions did the participants take/receive?
  Eligible study participants were randomly assigned to receive either palbociclib (125 mg) and fulvestrant (500 mg); or, placebo and fulvestrant (500 mg). Participants has a 66% (2 in 3) chance of receiving palbociclib and fulvestrant, and a 33% (1 in 3) chance of receiving fulvestrant and placebo. This was a double-blind study, which means neither the participants nor the study teams knew which of these study drug groups participants were assigned to. Participants who were not yet postmenopausal also received treatment with goserelin.

  What medical problems (adverse reactions) did the participants have?
  The most frequently (>25% of patients) reported adverse reactions in the palbociclib plus fulvestrant arm were:
  - Neutropenia (low number of white blood cells) (84.3%)
  - Leukopenia (low number of white blood cells) (60.3%)
  - Infections (55.1%)
  - Fatigue (43.8%)
  - Nausea (36.5%)
  - Anemia (32.2%)
  - Stomatitis (inflammation and pain in the inner cheeks, gums, lips and tongue) (31.0%)
  - Headache (29.6%)
  - Diarrhoea (loose stools) (27.5%),
  - Arthralgia (joint pain/stiffness) (26.1%)
  - Thrombocytopenia (low platelet levels in the blood [blood cells which help you to clot, stop bleeding]) (25.8%)

  The most frequently (>25% of patients) reported adverse reactions in the placebo plus fulvestrant arm were:
  - Infections (36.0%)
  - Fatigue (32.6%)
  - Nausea (30.2%)

  A list of all adverse reactions identified during the study, in either treatment arm, can be found in the CSR summary.

  What happened during this study and what were the results?
  Palbociclib plus fulvestrant was well tolerated and the majority of adverse reactions were non-serious and manageable, as evidenced by the low rates of permanent treatment discontinuation associated with treatment-related AEs. Cumulative safety data showed a consistent safety profile with long-term use for the palbociclib plus fulvestrant combination.

  How has this study helped patients and researchers?
  The results of this study will assist researchers in the development of future treatments for breast cancer, which will ultimately benefit patients with this disease.

  Details of any further research planned
  Details of any planned further research can be found at https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.pfizer.com%2F&data=05%7C01%7Capprovals%40hra.nhs.uk%7Ca35694f35a6a4e48430308db2ba5570d%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638151761344261828%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=%2FB%2FpUIaxQsx4IPfPhKkp0q07sdEAxB53KPmfX5ja1wk%3D&reserved=0

  Where can I learn more about this study?
  A description of this clinical trial will be available on https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DouFFm-2FZqrUn2jjUD5TieZI-2FsZrRvWoRm1AlKL65PC1isc2Hca0pqgMcOjozJrP5Fwjg9_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YJd1383XzwBjyOyccTFbo-2FAgFw1E9MNQwxSUgOtEjkux24ODcjerUCEadR8x4XTv9lLam7wVCSR8cymk9wdHd-2BGd7OgIL4C5LVxz43vzXlDWPzCF1VqEM7sp1uFprg9-2Fh8uOyLgYGtjlwFqbr8QTMeb8AjdIpQrRygyEfkiNeGwbg-3D-3D&data=05%7C01%7Capprovals%40hra.nhs.uk%7Ca35694f35a6a4e48430308db2ba5570d%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638151761344418058%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=u6Su3x44msNKf729V3qA0w2Apo3XjI0Jf2QzljRgkeU%3D&reserved=0 as required by U.S. Law. This Website will not include information that can identify participants.
  The research study results may also be found on https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.pfizer.com%2F&data=05%7C01%7Capprovals%40hra.nhs.uk%7Ca35694f35a6a4e48430308db2ba5570d%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638151761344418058%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=tOesg5a2OuaclAeV2G6N5tpRP1AzjzBzoTd2ojIIIUM%3D&reserved=0, https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agba4yu73OCS9U-2BkKS40W1kfYExOio4eP47B7HpAL43GEFeLuh_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YJd1383XzwBjyOyccTFbo-2FAedvBAKYBIImXhiWASbUHKHQUiHY8AHJZOTjERWLmAiUak-2Bpjg-2BX-2BZne0HP9yiV1UGaIRwjLaW1ysIyRQZeq1fwL-2F8bEPcGaDBdvHokFEVFOX2jCyD8fQAfq3cmpVnrfjGCOclv4KafD-2F1CQfug0FSQ-3D-3D&data=05%7C01%7Capprovals%40hra.nhs.uk%7Ca35694f35a6a4e48430308db2ba5570d%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638151761344418058%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=DxvuxPEZXIvGRyL9raP2QnTgoqON0JCS2qGPHDWgQLw%3D&reserved=0 and other public registries.

• REC name

  East of England - Cambridge South Research Ethics Committee

• REC reference

  14/EE/0035

• Date of REC Opinion

  12 Mar 2014

• REC opinion

  Further Information Favourable Opinion