Clinical Trials /

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

NCT02913430

Description:

To study progression free survival for treatment with Fulvestrant plus palbociclib compared to treatment with tamoxifen plus palbociclib in Metastatic Breast Cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase II Treatment of Metastatic Breast Cancer With Fulvestrant or Tamoxifen
  • Official Title: Treatment of Metastatic Breast Cancer With Fulvestrant or Tamoxifen: A Randomized Phase II 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

Purpose

To study progression free survival for treatment with Fulvestrant compared to treatment with tamoxifen in Metastatic Breast Cancer.

Detailed Description

The primary objectives are to compare progression-free survival (PFS) in fulvestrant and tamoxifen arms in patients unselected by ESR1 mutation, and in the subset of patients with ESR1-mt tumors assessed primarily from ctDNA at enrollment.

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 D15 of the first cycle (as a loading dose) or tamoxifen 20mg PO daily.

Trial Arms

NameTypeDescriptionInterventions
Arm AActive Comparatorfulvestrant administered 500mg IM Q28 days
  • Fulvestrant
    Arm BActive ComparatorTamoxifen is administered orally, at a dose of20mg PO Qdaily
      • Tamoxifen

    Eligibility Criteria

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

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

    4. Patients may have been previously treated with a CDK 4/6 inhibitor or mTOR inhibitor or other investigational agent in addition to an aromatase inhibitor.

    5. 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 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 allowable

    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 x upper limit of normal (ULN)

    2. AST ≤ 1.5 x ULN

    3. ALT ≤ 2.5 x ULN

    4. Alkaline phosphatase ≤ 2.5 x 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 x ULN.

    Exclusion Criteria:

    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 CDK 4/6 inhibitor, everolimus or other biological agent.

    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:Co-primary objectives to compare progression-free survival (PFS) in fulvestrant and tamoxifen arms in patients unselected by ESR1 mutation, and in the subset of patients with ESR1-mt tumors assessed primarily from ctDNA at enrollment.
    Time Frame:6 months after last subject is enrolled
    Safety Issue:
    Description:PFS is defined as the duration of time from time of randomization to time of progression or death, whichever occurs first. 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.

    Secondary Outcome Measures

    Measure:Response rate compared between the tamoxifen and fulvestrant arms in the entire cohort and in the ESR1-mt
    Time Frame:6 months after last patient enrolled
    Safety Issue:
    Description:
    Measure:Overall Survival compared between the tamoxifen and fulvestrant arms in the entire cohort and in the ESR1-mt
    Time Frame:5 years after study entry, or until all patients deceased
    Safety Issue:
    Description:
    Measure:Number of participants with treatment-related adverse events as assessed by CTCAE v. 4.0 in each treatment arm
    Time Frame:while on study treatment, estimate 6 months from study entry in all patients
    Safety Issue:
    Description:Treatment related adverse events will be assessed in all patients as assessed by CTCAE v4.0. This will be determined at the monthly visits.
    Measure:Clinical benefit rate (defined as CR+PR+ stable disease at any tumor assessment) and clinical benefit rate at 6 months (CBR6) (defined as CR+PR+ stable disease for at least 6 months)
    Time Frame:6 months after last subject is enrolled
    Safety Issue:
    Description:

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:University of Pittsburgh

    Trial Keywords

      Last Updated

      October 31, 2016