Clinical Trials /

Treatment of Metastatic Breast Cancer With Fulvestrant Plus Palbociclib or Tamoxifen Plus Palbociclib

NCT02913430

Description:

To assess longitudinal changes in allele frequency of ESR1 mutation in plasma in patients treated with Fulvestrant plus palbociclib compared to tamoxifen plus palbociclib

Related Conditions:
  • Invasive Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Treatment of Metastatic Breast Cancer With Fulvestrant Plus Palbociclib or Tamoxifen Plus Palbociclib
  • Official Title: Treatment of Metastatic Breast Cancer With Fulvestrant Plus Palbociclib or Tamoxifen Plus Palbociclib: A Randomized Pilot Trial With ESR1 Mutation Tested in Circulating Tumor DNA.

Clinical Trial IDs

  • ORG STUDY ID: 16-015
  • NCT ID: NCT02913430

Conditions

  • Metastatic Breast Cancer

Interventions

DrugSynonymsArms
FulvestrantArm A
TamoxifenArm B
PalbociclibArm A

Purpose

To assess longitudinal changes in allele frequency of ESR1 mutation in plasma in patients treated with Fulvestrant plus palbociclib compared to tamoxifen plus palbociclib

Detailed Description

      The primary objectives are to assess longitudinal changes in allele frequency of ESR1
      mutation in plasma in patients treated with Fulvestrant plus palbociclib compared to
      tamoxifen plus palbociclib.

      Patients with ER+ breast cancer who had 1 to 3 prior lines of endocrine therapy and up to one
      line of chemotherapy for MBC, excluding fulvestrant and tamoxifen, will be randomized in a
      1:1 ratio to receive fulvestrant 500mg IM Q28 days with one extra dose on Day15 of the first
      cycle (as a loading dose) plus palbociclib 125mg/day PO on a 21 days on/7 days off schedule
      or tamoxifen 20mg PO daily plus palbociclib 125mg/day PO on a 21 days on/7 days off schedule.
    

Trial Arms

NameTypeDescriptionInterventions
Arm AActive Comparatorfulvestrant administered 500mg IM Q28 days plus palbociclib125mg/day PO on a 21 days on/7 days off schedule
  • Fulvestrant
  • Palbociclib
Arm BActive ComparatorTamoxifen is administered orally, at a dose of20mg PO Qdaily plus palbociclib125mg/day PO on a 21 days on/7 days off schedule
  • Tamoxifen
  • Palbociclib

Eligibility Criteria

        For inclusion in the study subjects should fulfill the following criteria:

          1. Signed informed consent

          2. Patients must have histologically or cytologically confirmed invasive breast cancer
             that is ER+ (>1% staining) with radiographical or clinical evidence of metastatic
             disease

             a. Measurable and/or non-measurable disease

          3. Prior therapies:

               1. Patients must have previously received an aromatase inhibitor in the adjuvant,
                  neo-adjuvant or metastatic setting.

               2. Patients must have previously received palbociclib in the adjuvant, neo- adjuvant
                  or metastatic setting. If patient is currently taking palbociclib at time of
                  screening for the trial they may continue taking palbociclib.

               3. The minimum duration of AI in the adjuvant setting is 2 years.

               4. There is no minimum duration of AI in the metastatic setting or neoadjuvant
                  setting.

               5. Patients may have been previously treated with an mTOR inhibitor or other
                  investigational agent in addition to an aromatase inhibitor.

               6. Prior treatment with tamoxifen is allowed in the adjuvant setting provided that
                  it was followed by a minimum of 2 years of an AI.

          4. Brain metastasis is allowed if previously treated, stable and off steroids for a
             minimum of 56 days

          5. Age > 18 years

          6. Male or female breast cancer is allowed

          7. Patients may be pre- or post-menopausal; pre-menopausal patients must be on ovarian
             suppression and must be adequately suppressed on LHRH agonists with estradiol levels
             in the post-menopausal range

             a. Premenopausal patients cannot be pregnant and must agree to adequate birth control
             in addition to ovarian suppression. Agreement by the patient and/or partner to use
             highly effective, nonhormonal form of contraception or two effective forms of
             non-hormonal contraception. Contraception use should continue during the duration of
             study treatment and for at least 6 months after the last dose of study treatment.

          8. ECOG performance status 0-2

          9. Adequate bone marrow function as indicated by the following, within 14 days of
             enrollment:

               1. ANC ≥ 1500 cells/mm3

               2. Platelets ≥ 100,000 cells/ mm3

               3. Hemoglobin ≥ 9 g/dL

         10. Adequate liver function, as indicated by the following, within 14 days of enrollment.

               1. Total bilirubin 1.5 upper limit of normal (ULN)

               2. AST 1.5 ULN

               3. ALT ≤ 2.5 ULN

               4. Alkaline phosphatase ≤ 2.5 ULN with the following exception; ALP ≤ 5× ULN in
                  patients with bone metastases.

         11. Adequate hemostatic function as determined by PT, INR and aPTT < 1.5× ULN (unless on
             therapeutic coagulation, in which case the adequate level of anticoagulation will be
             determined by the investigator).

         12. Adequate renal function, as indicated by creatinine ≤ 1.5 ULN.

        Subjects should not enter the study if any of the following exclusion criteria are
        fulfilled

          1. Prior therapy exclusions:

               1. Prior therapy with fulvestrant

               2. Prior therapy with tamoxifen in the metastatic setting

               3. More than 3 prior lines of endocrine therapy in the metastatic setting

               4. More than one prior line of chemotherapy in the metastatic setting

          2. Washout of 2 weeks is required for aromatase inhibitors; washout of 4 weeks is
             required for, everolimus or other biological agents with the exception of Palbociclib.

          3. Patients must not be receiving any other investigational agent.

          4. Patients with symptomatic, untreated CNS metastases are not eligible.

          5. Patients may not have significant concurrent illness, infection, pregnancy or
             lactation

          6. Patients must not have a different active malignancy, except for skin basal cell
             carcinoma, skin squamous cell carcinoma and cervical intraepithelial neoplasia.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Changes in allele frequency of ESR1 mutation
Time Frame:Up to 6 months
Safety Issue:
Description:Assessment of longitudinal changes in allele frequency of ESR1 mutation (mt) in plasma in treated patients. ESR1 status will be assessed using ddPCR. Allelic frequency is quantified as compared to wild-type allele, independent of plasma volume. The range will be 0-100, with increased values indicating worse prognosis or disease progression.

Secondary Outcome Measures

Measure:Progression-free survival (PFS)
Time Frame:Up to 5 years
Safety Issue:
Description:The duration of time from time of randomization to time of progression or death, whichever occurs first. Disease progression (PD) as defined by RECIST v1.1: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The progression of non-target lesions or the appearance of one or more new lesions is also considered progression. PFS for a subject without an event will be censored on the date of last tumor assessment. If an interval of 6 months passes without a tumor assessment, PFS will be censored at the time of the earlier tumor assessment, even if an event (progressive disease or death) is later observed.
Measure:Objective Response Rate (ORR)
Time Frame:Up to 5 years
Safety Issue:
Description:The proportion of patients with tumor size reduction per RECIST v1.1 ((Complete Response + Partial Response (PR) / all patients assessed for response). Per RECIST v1.1, CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Measure:Clinical benefit rate (CBR)
Time Frame:Up to 5 years
Safety Issue:
Description:Clinical Benefit Rate is defined as the number of patients with Completed Response (CR)+Partial Response (PR)+ Stable Disease (SD) / all patients assessed for response per RECIST v1.1 . Per RECIST v1.1, CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Measure:Assessment ESR1 status
Time Frame:Up to 5 years
Safety Issue:
Description:Assessment of ESR1 status in plasma and biopsy samples. ESR1 status will be assessed using ddPCR. ESR1 status is quantified as compared to wild-type allele, independent of plasma volume. The range will be 0-100, with increased values indicating worse prognosis or disease progression.
Measure:Changes in circulating levels of ESR1-mt
Time Frame:Up to 5 years
Safety Issue:
Description:Assessment of longitudinal changes in circulating levels of ESR1-mt. The range will be 0-100, with increased values indicating worse prognosis or disease progression.
Measure:Gene expression via cfRNA
Time Frame:Up to 5 years
Safety Issue:
Description:Use of cfRNA to determine gene expression in AI resistant mutant ESR1 MBC.

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Shannon Puhalla

Trial Keywords

  • ESR1 mutation

Last Updated

December 1, 2020