A Phase II study of post-operative palbociclib as an alternative to chemotherapy in older patients with localized breast cancer at high risk of relapse

Phase 1

• Conditions: ocalized ER+ breast cancer; MedDRA version: 23.0Level: LLTClassification code 10070575Term: Estrogen receptor positive breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 23.0Level: LLTClassification code 10070577Term: Oestrogen receptor positive breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: HLTClassification code 10006290Term: Breast and nipple neoplasms malignantSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: HLGTClassification code 10006291Term: Breast neoplasms malignant and unspecified (incl nipple)System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: SOCClassification code 10029104Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps)System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-002553-30-PL
• Lead Sponsor: European Organisation for research and treatment of Cancer

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-03-27
• Last Update Posted: 12 March 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 0

Inclusion Criteria

- Women or men with pathologic stage II or stage III, early invasive breast cancer
according to the UICC 8th edition for TNM classification
- Histologically confirmed ER+ (at least 10 % of cells staining positive
for ER), HER-2 negative, early invasive breast cancer based on results of
local pathology. Testing may be performed on diagnostic core biopsy or
resection specimen.
- In patients with multicentric, multifocal and/or bilateral breast cancer,
all histopathologically examined invasive tumors must meet pathologic
criteria regarding ER and HER2-status described above.
- Adjuvant chemotherapy indicated and feasible according to treating
physician and patient, based on standard clinicopathological parameters
(tumor size, lymph node involvement, general health status,
proliferation marker, patient wish) and gene expression profile if
available.
- Adjuvant chemotherapy with both anthracycline and taxanes (in
combination or in sequence) considered not indicated or not feasible
according to treating physician.
- Age =70 years
- WHO Performance status 0-2
- Completed G8 geriatric assessment within 3 weeks of randomization.
- Participation in translational research is mandatory and therefore
patient must consent for it. Patient should allow sequential sampling of
blood during the course of the trial
- Patient must have undergone breast +/- axillary surgery with curative
intent for the current malignancy =12 weeks before randomization. The
final primary tumor surgical specimen must have R0 margins free from
tumor.
- Patients must have sufficient resolution of any surgical side effects
from the last surgery per physician assessment, with no active wound
healing complications at the time of randomization.
- Incentive to undergo adjuvant radiation therapy when indicated per
local institutional guidelines.
Note: For patients in the palbociclib arm, radiation therapy when
indicated has to start =13 weeks after last surgery. The endocrine
therapy can be initiated during or after the radiation therapy but not
later than 4 weeks after the last radiotherapy. Palbociclib has to start =4
weeks after the last radiotherapy. When radiation therapy is not
indicated, endocrine therapy and palbociclib have to be initiated =13
weeks after last surgery. Note: For patients in the chemotherapy arm,
chemotherapy has to be the first adjuvant treatment and has to start =
13 weeks after the last surgery. When radiation therapy is indicated, this
treatment has to start =9 weeks after the last chemotherapy
administration. Adjuvant endocrine therapy can be initiated during or
after the radiation therapy but not later than 4 weeks after the last
radiotherapy. When radiation therapy is not indicated, endocrine therapy
has to be initiated =6 weeks after last chemotherapy administration.
- Adequate baseline organ function, evidenced by the following
laboratory results within 3 weeks of randomization:
- Hemoglobin = 9 g/dL
- Absolute neutrophil count (ANC) = 1500/mm3
- Platelet count = 100,000/mm3
- Total bilirubin = 1.5 upper limit of normal (ULN), or total bilirubin = 3.0
×ULN in patients with documented Gilbert's Syndrome.
- Glomerular Filtration Rate (GFR) = 30 ml/min according to MDRD
formula or CKD-EPI formula or Cockcroft and Gault formula
- SGOT (AST), SGPT (ALT) and alkaline phosphatase = 2.5 × ULN
- Patients must be able and willing to swallow and retain oral medication
without a condition that would interfere with enteric absorption.
For men participating in the

Exclusion Criteria

- Evidence of macroscopic distant metastases, investigated according to
local institutional guidelines.
- Previous history of invasive breast cancer
- Systemic anticancer therapy prior to the breast cancer surgery
- Prior therapy with any CDK4/6 inhibitor
- Concurrent investigational agent within 28 days of randomization or
five elimination half-lives, whichever is longer
- Concomitant anticancer treatment with the exception of bone
antiresorptive agents or LHRH agonists in male patients treated with an
aromatase-inhibitor
- History of allergic reactions attributed to compounds of chemical or
biological composition similar to palbociclib or to chemotherapy
components
- Patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption
- Medications or substances that are potent inhibitors or inducers of
CYP3A isoenzymes within 7 days of randomization
- History of extensive disseminated/bilateral or known presence of
interstitial fibrosis or interstitial lung disease, including a history of
pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia,
interstitial lung disease, obliterative bronchiolitis, and pulmonary
fibrosis, but not history of prior radiation pneumonitis.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (including known HIV, active hepatitis B and/or
hepatitis C infection), symptomatic congestive heart failure, unstable
angina pectoris, uncontrolled cardiac arrhythmia, or uncontrolled
diabetes.
Note: For patients for whom doxorubicin or epirubicin is planned, an
adequate baseline cardiac function (left ventricular ejection fraction =
50%) should have been proven no more than 1 year before treatment
start.
- Any psychological, familial, sociological or geographical condition
potentially hampering compliance with the study protocol and follow-up
schedule; those conditions should be discussed with the patient before
registration in the trial
- Other malignancy within the last 5 years except: adequately treated
non-metastatic non-melanoma skin cancer, or successfully treated in situ carcinoma for example curatively treated in situ
cancer of the cervix, ductal carcinoma in situ of the breast.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified