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

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ClinicalTrials.gov Identifier: NCT02913430
Recruitment Status : Recruiting
First Posted : September 23, 2016
Last Update Posted : August 14, 2019
Sponsor:
Information provided by (Responsible Party):
Shannon Puhalla, University of Pittsburgh

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

Condition or disease Intervention/treatment Phase
Metastatic Breast Cancer Drug: Fulvestrant Drug: Tamoxifen Drug: Palbociclib Phase 2

Detailed Description:

The primary objectives are to compare progression-free survival (PFS) in in fulvestrant plus palbociclib and tamoxifen plus palbociclib 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 2 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) plus palbociclib125mg/day PO on a 21 days on/7 days off schedule or tamoxifen 20mg PO daily plus palbociclib125mg/day PO on a 21 days on/7 days off schedule .


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Treatment of Metastatic Breast Cancer With Fulvestrant Plus Palbociclib or Tamoxifen Plus Palbociclib: A Randomized Phase II Trial With ESR1 Mutation Tested in Circulating Tumor DNA.
Actual Study Start Date : April 24, 2018
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : March 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Active Comparator: Arm A
fulvestrant administered 500mg IM Q28 days plus palbociclib125mg/day PO on a 21 days on/7 days off schedule
Drug: Fulvestrant
500mg IM Q28 days

Drug: Palbociclib
Tamoxifen or Fulvestrant plus palbociclib125mg/day PO on a 21 days on/7 days off schedule

Active Comparator: Arm B
Tamoxifen is administered orally, at a dose of20mg PO Qdaily plus palbociclib125mg/day PO on a 21 days on/7 days off schedule
Drug: Tamoxifen
20mg PO Qdaily

Drug: Palbociclib
Tamoxifen or Fulvestrant plus palbociclib125mg/day PO on a 21 days on/7 days off schedule




Primary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: up to 6 months after last subject is enrolled ]
    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 :
  1. Response Rate [ Time Frame: up to 6 months after last patient enrolled ]
  2. Overall Survival (OS) [ Time Frame: up 5 years after study entry ]
  3. 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 ]
    Treatment related adverse events will be assessed in all patients as assessed by CTCAE v4.0. This will be determined at the monthly visits.

  4. Clinical benefit rate (CBR) [ Time Frame: up to 6 months after last subject is enrolled ]
    defined as CR+PR+ stable disease at any tumor assessment


Other Outcome Measures:
  1. Assessment of concordance of ESR1 status in plasma and biopsy samples [ Time Frame: 6 months after last subject is enrolled ]
  2. Assessment of longitudinal changes in circulating levels of ESR1-mt and correlation with response [ Time Frame: 6 months after last subject is enrolled ]
  3. Assessment of concordance with metastatic biopsies and archived primary tumor samples, determination of ESR1 status at diagnosis in archived tumor samples. [ Time Frame: 6 months after last subject is enrolled ]
  4. Assessment of the functionality of ESR1 in tumor biopsies collected prior to and following treatment with fulvestrant as assessed by RNAseq [ Time Frame: 12 months after last subject is enrolled ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
    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 1.5upper limit of normal (ULN)
    2. AST 1.5 X ULN
    3. ALT ≤ 2.5X ULN
    4. Alkaline phosphatase ≤ 2.5X ULN with the following exception; ALP ≤ 5X ULN in patients with bone metastases.
  11. Adequate hemostatic function as determined by PT, INR and aPTT < 1.5X 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 ≤ 1.5X ULN. Subjects should not enter the study if any of the following exclusion criteria are fulfilled

1. Prior therapy exclusions:

a. Prior therapy with fulvestrant b. Prior therapy with tamoxifen in the metastatic setting c. More than 3 prior lines of endocrine therapy in the metastatic setting d. 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.

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02913430


Contacts
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Contact: Kristina Sherman, BSN 412-641-6374 shermank4@upmc.edu
Contact: Deborah Check, BSN 412-641-1840 checkda@upmc.edu

Locations
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United States, Pennsylvania
Magee-Womens Hospital UPMC Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Shannon Puhalla, MD    412-641-2357    puhallasl@mail.magee.edu   
Contact: Kristina Sherman, BSN    412-641-6374    shermank4@upmc.edu   
Sponsors and Collaborators
University of Pittsburgh
Investigators
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Principal Investigator: Shannon Puhalla, MD University of Pittsburgh

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Responsible Party: Shannon Puhalla, Assistant Professor of Medicine, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT02913430     History of Changes
Other Study ID Numbers: 16-015
First Posted: September 23, 2016    Key Record Dates
Last Update Posted: August 14, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Tamoxifen
Fulvestrant
Palbociclib
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Bone Density Conservation Agents
Estrogen Receptor Antagonists
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action