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

NCT ID: NCT02913430

Last Updated: 2024-09-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-04-24
• Study Completion Date: 2024-04-30

Brief Summary

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.

Conditions

Metastatic Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A

fulvestrant administered 500mg IM Q28 days plus palbociclib125mg/day PO on a 21 days on/7 days off schedule

Group Type: ACTIVE_COMPARATOR

Fulvestrant

Intervention Type: DRUG

500mg IM Q28 days

Palbociclib

Intervention Type: DRUG

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

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

Group Type: ACTIVE_COMPARATOR

Tamoxifen

Intervention Type: DRUG

20mg PO Qdaily

Palbociclib

Intervention Type: DRUG

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

Interventions

Fulvestrant

500mg IM Q28 days

Intervention Type: DRUG

Tamoxifen

20mg PO Qdaily

Intervention Type: DRUG

Palbociclib

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

Intervention Type: DRUG

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. 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.

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, 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shannon Puhalla

OTHER

Sponsor Role: lead

Responsible Party

Shannon Puhalla

Assistant Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Shannon Puhalla, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

Magee-Womens Hospital UPMC

Pittsburgh, Pennsylvania, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

HCC 16-015

Identifier Type: -

Identifier Source: org_study_id