Clinical Trials /

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

NCT03560856

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Biomarker Study of Palbociclib + Fulvestrant for Second, and Third Line of Postmenopausal Women With hr+/her2- Advanced Breast Cancer
  • Official Title: A Biomarker Study of Palbociclib + Fulvestrant for Second, and Third Line of Postmenopausal Women With hr+/her2- Advanced Breast Cancer (PALPETBIO)

Clinical Trial IDs

  • ORG STUDY ID: P170104J
  • NCT ID: NCT03560856

Conditions

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

Interventions

DrugSynonymsArms
Fulvestrant + palbociclibFulvestrant 500mg + palbociclib 125 mg

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Fulvestrant 500mg + palbociclib 125 mgOtherPatients 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 + palbociclib

Eligibility Criteria

        Inclusion Criteria:

          1. 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.

          2. 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.

          3. 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.

          4. 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.

          5. 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

          6. Except where prohibited by local regulations, all patients must agree to provide and
             have available a formalin-fixed paraffin embedded (FFPE) tissue biopsy taken at the
             time of presentation with recurrent or metastatic disease. A frozen de novo tissue
             biopsy is required at inclusion and at progression in a visceral, skin or lymph node
             lesion

          7. Patient must have measurable lesions (according to RECIST 1.1)

             • Patients with only osteoblastic bone lesions are not eligible

          8. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

          9. Patients must be treated by palbociclib+fulvestrant according to their Summary of
             Product Characteristics (SmPC) described bellow as a reminder :

             Adequate organ and marrow function defined as follows:

               -  ANC >1,500/mm3 (1.5 x 109/L);

               -  Platelets >100,000/mm3 (100 x 109/L);

               -  Hemoglobin > 9 g/dL (90 g/L);

               -  Serum creatinine <1.5 x Upper Limit of Normal (ULN) or estimated creatinine
                  clearance >60 ml/min as calculated using the method standard for the institution;

               -  Total serum bilirubin <1.5 x ULN (<3 ULN if Gilbert's disease);

               -  AST and/or ALT <3 x ULN (<5.0 x ULN if liver metastases present);

               -  Alkaline phosphatase <2.5 x ULN (<5 x ULN if bone or liver metastases present).

         10. Resolution of all acute toxic effects of prior therapy or surgical procedures to
             National Cancer Institute (NCI) CTCAE Grade <1 (except alopecia).

         11. Evidence of a personally signed and dated informed consent document indicating that
             the patient has been informed of all pertinent aspects of the study.

         12. Patients who are willing and able to comply with scheduled visits, treatment plan,
             laboratory tests, and other study procedures.

         13. Patients covered by health insurance

        Exclusion Criteria:

          1. Prior treatment with any Cyclin-Dependent Kinase (CDK) inhibitor or fulvestrant will
             not be allowed. Previous treatment with Everolimus will be allowed.

          2. 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).

          3. Known active uncontrolled or symptomatic Central Nervous System (CNS) metastases,
             carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms,
             cerebral edema, and/or progressive growth. Patients with a history of CNS metastases
             or cord compression are eligible if they have been definitively treated (eg,
             radiotherapy, stereotactic surgery) and are clinically stable off anticonvulsants and
             steroids for at least 4 weeks before inclusion.

          4. Diagnosis of any other malignancy within 3 years prior to inclusion, except for
             adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of
             the cervix.

          5. 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.

               -  major surgery, chemotherapy, radiotherapy, any investigational agents, or other
                  anti-cancer therapy within 2 weeks before inclusion. Patients who received prior
                  radiotherapy to >25% of bone marrow are not eligible independent of when it was
                  received.

               -  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.

               -  any of the following within 6 months of inclusion: myocardial infarction,
                  severe/unstable angina, ongoing cardiac dysrhythmias of NCI CTCAE Grade <2,
                  atrial fibrillation of any grade, coronary/peripheral artery bypass graft,
                  symptomatic congestive heart failure, cerebrovascular accident including
                  transient ischemic attack, or symptomatic pulmonary embolism.

               -  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.

          6. 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.

          7. 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.

          8. Participation in other studies involving investigational drug(s) (Phases 1-4) within 4
             weeks before inclusion in the current study.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free survival
Time Frame:2 years
Safety Issue:
Description: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

Secondary Outcome Measures

Measure:Overall survival
Time Frame:2 years
Safety Issue:
Description:Overall Survival is defined as the time from the date of inclusion to the date of the death due to any cause
Measure:Response
Time Frame:2 years
Safety Issue:
Description:Objective Response (OR) defined by Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) at 2 years.
Measure:Clinical Benefit Response
Time Frame:24 weeks
Safety Issue:
Description:Clinical Benefit Response (CBR): Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) at week 24.
Measure:Duration of Response (DoR).
Time Frame:2 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Assistance Publique - Hôpitaux de Paris

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