search
Back to results

Preoperative Palbociclib in Patients With DCIS of the Breast That Are Candidates for Surgery (WI223281)

Primary Purpose

DCIS

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Palbociclib
Sponsored by
Georgetown University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for DCIS focused on measuring Breast Cancer, DCIS, Ductal Carcinoma In Situ, Palbociclib

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria for all patients (Groups A and B):

  • Signed informed consent obtained prior to any study specific assessments and procedures
  • Age ≥18 years
  • Premenopausal and postmenopausal women, or men
  • Current pathologic diagnosis of DCIS of the breast of any receptor status; History of previous DCIS allowed provided that the patient is currently off systemic risk-reduction endocrine therapy; History of previous invasive breast cancer adequately treated and that is currently in remission and unrelated to current DCIS (based on primary tumor location) is allowed as long as patient is currently off systemic therapy for that invasive cancer for at least 4 weeks prior to pre-treatment biopsy (diagnostic biopsy); Patients with multifocal or multicentric lesions are allowed, as long as at least one lesion is histologically confirmed DCIS and overall clinical AJCC Stage 0 or I.
  • A formalin-fixed paraffin-embedded (FFPE) tumor tissue block from diagnostic biopsy must be transmitted to MedStar Georgetown University Hospital Pathology Department repository and confirmation of receipt must be available prior to enrollment.
  • Positive Rb by immunohistochemistry in the DCIS component of the lesion - must be performed at CLIA-approved setting (for instance, MGUH); Rb staining will be considered positive when 1+ or above (in a scale of 0, 1+, 2+ or 3+)
  • In the absence of histologic diagnosis of DCIS, patient may undergo fresh biopsy for eligibility, provided: this invasive procedure is not a Fine Needle Aspiration (FNA); AND this procedure is a core biopsy, stereotactic biopsy or incisional biopsy of the suspicious breast lesion; AND the primary lesion is not completely resected during the procedure.
  • The patient is candidate for and is willing to receive definitive surgical therapy for DCIS
  • ECOG performance status 0-1
  • Willingness to provide a sample of tissue collected at definitive surgery for research

Inclusion criteria specific to treatment Group A:

  • Patients must be able and willing to swallow and retain oral medication
  • Absolute neutrophil count (ANC) ≥ 1,500/mm3
  • Platelets ≥ 120,000/mm3
  • Hemoglobin ≥ 10g/dL
  • Total serum bilirubin ≤ ULN; or total bilirubin ≤ 3.0 × ULN with direct bilirubin within normal range in patients with documented Gilbert's Syndrome.
  • Aspartate amino transferase (AST or SGOT) and alanine amino transferase (ALT or SGPT) ≤ 1.5 × institutional ULN
  • Serum creatinine within normal institutional limits or creatinine clearance ≥ 50 mL/min/1.73 m2 for patients with serum creatinine levels above institutional ULN.
  • Pregnancy must be ruled out: serum or urine pregnancy test must be negative within 14 days of treatment start in women of childbearing potential. Pregnancy testing does not need to be pursued in patients who are judged as postmenopausal before enrollment, or who have undergone tubal ligation, bilateral oophorectomy, total hysterectomy.
  • Willingness to undergo adequate contraception if childbearing potential; women of childbearing potential and male patients randomized into treatment Group A must use adequate contraception for the duration of protocol treatment and for 3 months after the last treatment with palbociclib if they are in Group A; adequate contraception is defined as one highly effective form (i.e. abstinence, (fe)male sterilization) OR two effective forms (e.g. non-hormonal IUD and condom / occlusive cap with spermicidal foam / gel / film / cream / suppository).

Exclusion Criteria for all patients (Groups A and B):

  • Concurrent therapy with other Investigational Products
  • Invasive carcinoma present in the diagnostic biopsy, microinvasion is allowed
  • Uncontrolled intercurrent illness including (active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, diabetes, pulmonary embolism in the past 6 months, or psychiatric illness/social situations that would limit compliance with study requirements).
  • Unable to comply with study requirements
  • Hormone therapies containing estrogen, progesterone, GnRH agonists and antagonists within 4 weeks from diagnostic biopsy.
  • Therapy with any CDK inhibitor in the past 3 months

Exclusion criteria specific to treatment Group A:

  • History of allergic reactions attributed to compounds of chemical or biologic composition similar to palbociclib
  • Presence of a condition that would interfere with enteric absorption of palbociclib
  • Pregnant women, or women of childbearing potential without a negative pregnancy test (serum or urine) within 7 days prior to enrollment; breastfeeding must be discontinued prior to study entry (Group A only).
  • Patients on combination antiretroviral therapy, i.e. those who are HIV+ (potential for pharmacokinetic interactions or increased immunosuppression with palbociclib).
  • Patients receiving any medications or substances that are potent inhibitors or inducers of CYP3A isoenzymes within 7 days of enrollment or during participation on study
  • Patients with clinically significant history of liver disease, including viral or other known hepatitis, current alcohol abuse, or cirrhosis, etc.

Sites / Locations

  • MedStar Georgetown University HospitalRecruiting
  • Medstar Washington Hospital CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Group A

Group B

Arm Description

Patients enrolled to Group A will receive a 12-day course of Palbociclib before surgery. They will receive Palbociclib 100mg PO daily x 12 days.

These patients will receive no pre-operative treatment. Core biopsies from diagnosis and material from definitive surgery will be collected for translational studies and tissue banking. They will also provide blood samples at screening and prior to definitive surgery.

Outcomes

Primary Outcome Measures

Feasibility: recruitment rates
The approach will be considered feasible if more than 50% of the enrolled patients are treated and followed within protocol rules, if collected samples are suitable for studies, and if pathologic changes are detectable when comparing diagnostic and surgical specimens, or treated and untreated specimens. In Group A, patients will be treated with palbociclib alone, providing the opportunity to address if proposing this kind of treatment for these patients is feasible. Obtaining human data and feasibility data would be key for designing efficacy/definitive studies of palbociclib in DCIS. This will be measured through data collected on eCRFs regarding timeline from consent to treatment, and treatment to surgery, including treatment delivery (beginning date, end date, number of tablets taken) and date of definitive surgery, as well as number of drop outs.

Secondary Outcome Measures

Pathology: descriptive findings on H&E
Pharmacodynamic effects as measured by changes in tissue morphology (evaluated by H&E) in pre- and post-dose tumor specimens
Pathology: descriptive findings on IHC
Pharmacodynamic effects as measured by changes in biomarkers Cdk4, Cdk6, pRb, Cyclin D1, Cyclin E (evaluated by IHC) in pre- and post-dose tumor specimens.
Toxicity based on CTCAE
Will be evaluated by CTCAE. There is no plan to compare Groups A and B regarding efficacy or toxicity. Toxicity will be descriptive for each treatment group, independently.

Full Information

First Posted
March 15, 2018
Last Updated
January 23, 2023
Sponsor
Georgetown University
Collaborators
Pfizer
search

1. Study Identification

Unique Protocol Identification Number
NCT03535506
Brief Title
Preoperative Palbociclib in Patients With DCIS of the Breast That Are Candidates for Surgery
Acronym
WI223281
Official Title
Preoperative Palbociclib in Patients With DCIS of the Breast That Are Candidates for Surgery
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 8, 2018 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
March 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Georgetown University
Collaborators
Pfizer

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a feasibility study which will evaluate the effects of pre-operative treatment of DCIS of the breast with palbociclib. Patients with biopsy-proven DCIS are eligible for the study. There will be 2 independent and unrelated study groups of 12 patients each, for a total of 24 patients: Group A, of male or female patients treated with palbociclib single agent (n=12); Group B, untreated, of male or female patients who consented translational studies in blood, as well as diagnostic and definitive surgical specimen, but not the pre-operative treatment with palbociclib (n=12).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
DCIS
Keywords
Breast Cancer, DCIS, Ductal Carcinoma In Situ, Palbociclib

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Group A
Arm Type
Experimental
Arm Description
Patients enrolled to Group A will receive a 12-day course of Palbociclib before surgery. They will receive Palbociclib 100mg PO daily x 12 days.
Arm Title
Group B
Arm Type
No Intervention
Arm Description
These patients will receive no pre-operative treatment. Core biopsies from diagnosis and material from definitive surgery will be collected for translational studies and tissue banking. They will also provide blood samples at screening and prior to definitive surgery.
Intervention Type
Drug
Intervention Name(s)
Palbociclib
Other Intervention Name(s)
Ibrance
Intervention Description
Palbociclib capsules for oral administration contain 125 mg, 100 mg, or 75 mg of palbociclib, a kinase inhibitor.
Primary Outcome Measure Information:
Title
Feasibility: recruitment rates
Description
The approach will be considered feasible if more than 50% of the enrolled patients are treated and followed within protocol rules, if collected samples are suitable for studies, and if pathologic changes are detectable when comparing diagnostic and surgical specimens, or treated and untreated specimens. In Group A, patients will be treated with palbociclib alone, providing the opportunity to address if proposing this kind of treatment for these patients is feasible. Obtaining human data and feasibility data would be key for designing efficacy/definitive studies of palbociclib in DCIS. This will be measured through data collected on eCRFs regarding timeline from consent to treatment, and treatment to surgery, including treatment delivery (beginning date, end date, number of tablets taken) and date of definitive surgery, as well as number of drop outs.
Time Frame
14 - 40 Days
Secondary Outcome Measure Information:
Title
Pathology: descriptive findings on H&E
Description
Pharmacodynamic effects as measured by changes in tissue morphology (evaluated by H&E) in pre- and post-dose tumor specimens
Time Frame
14 - 40 Days
Title
Pathology: descriptive findings on IHC
Description
Pharmacodynamic effects as measured by changes in biomarkers Cdk4, Cdk6, pRb, Cyclin D1, Cyclin E (evaluated by IHC) in pre- and post-dose tumor specimens.
Time Frame
14 - 40 Days
Title
Toxicity based on CTCAE
Description
Will be evaluated by CTCAE. There is no plan to compare Groups A and B regarding efficacy or toxicity. Toxicity will be descriptive for each treatment group, independently.
Time Frame
14 - 40 Days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria for all patients (Groups A and B): Signed informed consent obtained prior to any study specific assessments and procedures Age ≥18 years Premenopausal and postmenopausal women, or men Current pathologic diagnosis of DCIS of the breast of any receptor status; History of previous DCIS allowed provided that the patient is currently off systemic risk-reduction endocrine therapy; History of previous invasive breast cancer adequately treated and that is currently in remission and unrelated to current DCIS (based on primary tumor location) is allowed as long as patient is currently off systemic therapy for that invasive cancer for at least 4 weeks prior to pre-treatment biopsy (diagnostic biopsy); Patients with multifocal or multicentric lesions are allowed, as long as at least one lesion is histologically confirmed DCIS and overall clinical AJCC Stage 0 or I. A formalin-fixed paraffin-embedded (FFPE) tumor tissue block from diagnostic biopsy must be transmitted to MedStar Georgetown University Hospital Pathology Department repository and confirmation of receipt must be available prior to enrollment. Positive Rb by immunohistochemistry in the DCIS component of the lesion - must be performed at CLIA-approved setting (for instance, MGUH); Rb staining will be considered positive when 1+ or above (in a scale of 0, 1+, 2+ or 3+) In the absence of histologic diagnosis of DCIS, patient may undergo fresh biopsy for eligibility, provided: this invasive procedure is not a Fine Needle Aspiration (FNA); AND this procedure is a core biopsy, stereotactic biopsy or incisional biopsy of the suspicious breast lesion; AND the primary lesion is not completely resected during the procedure. The patient is candidate for and is willing to receive definitive surgical therapy for DCIS ECOG performance status 0-1 Willingness to provide a sample of tissue collected at definitive surgery for research Inclusion criteria specific to treatment Group A: Patients must be able and willing to swallow and retain oral medication Absolute neutrophil count (ANC) ≥ 1,500/mm3 Platelets ≥ 120,000/mm3 Hemoglobin ≥ 10g/dL Total serum bilirubin ≤ ULN; or total bilirubin ≤ 3.0 × ULN with direct bilirubin within normal range in patients with documented Gilbert's Syndrome. Aspartate amino transferase (AST or SGOT) and alanine amino transferase (ALT or SGPT) ≤ 1.5 × institutional ULN Serum creatinine within normal institutional limits or creatinine clearance ≥ 50 mL/min/1.73 m2 for patients with serum creatinine levels above institutional ULN. Pregnancy must be ruled out: serum or urine pregnancy test must be negative within 14 days of treatment start in women of childbearing potential. Pregnancy testing does not need to be pursued in patients who are judged as postmenopausal before enrollment, or who have undergone tubal ligation, bilateral oophorectomy, total hysterectomy. Willingness to undergo adequate contraception if childbearing potential; women of childbearing potential and male patients randomized into treatment Group A must use adequate contraception for the duration of protocol treatment and for 3 months after the last treatment with palbociclib if they are in Group A; adequate contraception is defined as one highly effective form (i.e. abstinence, (fe)male sterilization) OR two effective forms (e.g. non-hormonal IUD and condom / occlusive cap with spermicidal foam / gel / film / cream / suppository). Exclusion Criteria for all patients (Groups A and B): Concurrent therapy with other Investigational Products Invasive carcinoma present in the diagnostic biopsy, microinvasion is allowed Uncontrolled intercurrent illness including (active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, diabetes, pulmonary embolism in the past 6 months, or psychiatric illness/social situations that would limit compliance with study requirements). Unable to comply with study requirements Hormone therapies containing estrogen, progesterone, GnRH agonists and antagonists within 4 weeks from diagnostic biopsy. Therapy with any CDK inhibitor in the past 3 months Exclusion criteria specific to treatment Group A: History of allergic reactions attributed to compounds of chemical or biologic composition similar to palbociclib Presence of a condition that would interfere with enteric absorption of palbociclib Pregnant women, or women of childbearing potential without a negative pregnancy test (serum or urine) within 7 days prior to enrollment; breastfeeding must be discontinued prior to study entry (Group A only). Patients on combination antiretroviral therapy, i.e. those who are HIV+ (potential for pharmacokinetic interactions or increased immunosuppression with palbociclib). Patients receiving any medications or substances that are potent inhibitors or inducers of CYP3A isoenzymes within 7 days of enrollment or during participation on study Patients with clinically significant history of liver disease, including viral or other known hepatitis, current alcohol abuse, or cirrhosis, etc.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Candace Mainor, MD
Phone
202-444-2223
Email
Candace.Mainor@gunet.georgetown.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Antonella Novielli, RN, MSN
Phone
202-784-3923
Email
noviella@georgetown.edu
Facility Information:
Facility Name
MedStar Georgetown University Hospital
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nellie Novielli, RN
Phone
202-784-3923
Email
noviella@georgetown.edu
First Name & Middle Initial & Last Name & Degree
Candace Mainor, MD
Facility Name
Medstar Washington Hospital Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stacy Malloy
Phone
202-877-9374
Email
stacy.k.malloy@medstar.net
First Name & Middle Initial & Last Name & Degree
Christopher Gallagher, MD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Preoperative Palbociclib in Patients With DCIS of the Breast That Are Candidates for Surgery

We'll reach out to this number within 24 hrs