A Biomarker Study of Palbociclib + Fulvestrant for Second, and Third Line of Postmenopausal Women With hr+/her2- Advanced Breast Cancer

NCT03560856 | Unknown Phase 2 DMC

• 1 other identifier: P170104J
• Study Type: interventional
• Target: 54
• Locations: 0 countries
• Sites: N/A

Brief Summary

The clinical efficacy of fulvestrant and/or palbociclib in the population of patients with metastatic lesions harboring ESR1 mutations was reported. In the PALOMA 3 study, the combination of Fulvestrant+ Palbociclib seems to be active in patients whose tumour harbours ESR1 mutations. This study will confirm these data on this population and will allow us to identify if other gene alterations or a genomic signature can correlate with fulvestrant +palbociclib resistance.

Conditions

Breast Cancer; HR+/HER2-negative Breast Cancer; Metastasis

Outcome Measures

Primary Outcomes (1)

• Progression Free survival

  Progression-Free Survival is defined as the time from the date of inclusion to the date of the first documentation of objective progression of disease (PD) or death due to any cause in the absence of documented PD

  2 years

Secondary Outcomes (4)

• Overall survival

  2 years

• Response

  2 years

• Clinical Benefit Response

  24 weeks

• Duration of Response (DoR).

  2 years

Study Arms (1)

Fulvestrant 500mg + palbociclib 125 mg

OTHER

Patients will be treated by Fulvestrant 500mg (day 1 and day 15) and then on Day 1 of each subsequent cycle and every 28 days with palbociclib 125 mg daily for 3 weeks on/1 week off (3/1 schedule).

Drug: Fulvestrant + palbociclib

Interventions

Fulvestrant + palbociclib DRUG

Patients will be treated by Fulvestrant 500mg (day 1 and day 15) and then on Day 1 of each subsequent cycle and every 28 days with palbociclib 125 mg daily for 3 weeks on/1 week off (3/1 schedule).

Fulvestrant 500mg + palbociclib 125 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women 18 years of age or older, who are either:
• Postmenopausal, as defined by at least one of the following criteria:
• Age \> 60 years;
• Age \<60 years and cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and serum estradiol and Follicle-Stimulating Hormone (FSH) level within the laboratory's reference range for postmenopausal females;
• Documented bilateral oophorectomy;
• Medically confirmed ovarian failure.
• Histologically or cytologically proven diagnosis of breast cancer with evidence of metastatic or locally advanced disease, not amenable to resection or radiation therapy with curative intent.
• Documentation of ER-positive and/or PR-positive tumor (\>10% positive stained cells) based on most recent tumor biopsy utilizing an assay consistent with local standards.
• Documented HER2-negative tumor based on local testing on most recent tumor biopsy:
• HER2-negative tumor is determined as immunohistochemistry score 0/1+ or negative by in situ hybridization (FISH/CISH/SISH) defined as a HER2/CEP17 ratio \<2 or for single probe assessment a HER2 copy number \<4.
• Patients must satisfy the following criteria for prior therapy:
• Progressed while on or within 1 month after the end of prior aromatase inhibitor therapy for advanced/metastatic breast cancer if postmenopausal.
• One previous line of chemotherapy for advanced/metastatic disease is allowed in addition to endocrine therapy as a maintenance therapy.
• Endocrine therapy required being the most recent treatment.
• Patients could have been treated by EVEROLIMUS

You may not qualify if:

• Prior treatment with any Cyclin-Dependent Kinase (CDK) inhibitor or fulvestrant will not be allowed. Previous treatment with Everolimus will be allowed.
• Patients with advanced/metastatic, symptomatic, visceral spread, that are at risk of life-threatening complications in the short term (including patients with massive uncontrolled effusions \[pleural, pericardial, peritoneal\], pulmonary lymphangitis, and over 50% liver involvement).
• Patient with at least one criteria for not receiving palbociclib and/or fulvestrant described bellow as a reminder :
• current use of food or drugs known to be potent CYP3A4 inhibitors, drugs known to be potent CYP3A4 inducers, and drugs that are known to prolong the QT interval.
• QTc interval \>480 msec (based on the mean value of the triplicate ECGs), family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation or Torsade de Pointes.
• impairment of gastro-intestinal (GI) function or GI disease that may significantly alter the absorption of palbociclib, such as history of GI surgery with may result in intestinal blind loops and patients with clinically significant gastroparesis, short bowel syndrome, unresolved nausea, vomiting, active inflammatory bowel disease or diarrhea of CTCAE Grade \>1.
• prior hematopoietic stem cell or bone marrow transplantation.
• known abnormalities in coagulation such as bleeding diathesis, or treatment with anticoagulants precluding intramuscular injections of fulvestrant.
• known or possible hypersensitivity to fulvestrant or to any palbociclib excipients.
• known human immunodeficiency virus infection.
• Other severe acute or chronic medical or psychiatric condition, including recent or active suicidal ideation or behavior, or laboratory abnormality that may increase the risk associated with study participation or palbociclib+fulvestrant administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
• Patients who are investigational site staff members directly involved in the conduct of the trial and their family members, site staff members otherwise supervised by the Investigator, or patients who are Pfizer employees directly involved in the conduct of the trial.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Interventions

Fulvestrant; palbociclib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Central Study Contacts

TEIXEIRA LUIS, MD PhD

CONTACT

142499613; luis.teixeira@aphp.frluis.teixeira@aphp.fr

Matthieu RESCHE-RIGON, MD PhD

CONTACT

142499742; matthieu.resche-rigon@univ-paris-diderot.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2018
• First Posted: June 18, 2018
• Study Start: June 27, 2018
• Primary Completion: June 1, 2022
• Study Completion: June 1, 2022
• Last Updated: June 18, 2018

Record last verified: 2018-05