PALBOCICLIB for Hormone receptor-positive HER2-negative early breast cancer

Inclusion criteria

• {"criterion_text":"- (1) Signed informed consent obtained prior to any study specific assessments and procedures."}
• {"criterion_text":"- (10) Serum or urine pregnancy test must be negative within 7 days of randomization in women of childbearing potential. Pregnancy testing does not need to be pursued in patients who are judged as postmenopausal before randomization, as determined by local practice, or who have undergone bilateral oophorectomy, total hysterectomy, or bilateral tubal ligation. Women of childbearing potential and male patients randomized into treatment Arm A or B must use adequate contraception for the duration of protocol treatment and for 6 months after the last treatment with palbociclib if they are in arm A. In addition, patients receiving standard adjuvant endocrine therapy (Arm A and Arm B) should use adequate contraception in accordance with the specific medication requirements (e.g. SmPC)."}
• {"criterion_text":"- (11) Patients may or may not have received neo/adjuvant therapy, but must be after last dose of chemotherapy and/or biologic therapy and must have sufficient resolution of side effects per physician assessment at the time of randomization."}
• {"criterion_text":"- (12) Patients may or may not have received breast/axilla/postmastectomy chest wall radiotherapy, but must be after last dose of radiotherapy and must have sufficient resolution of side effects per physician assessment at the time of randomization."}
• {"criterion_text":"- (13) 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."}
• {"criterion_text":"- (14) Patients must either be initiating or have already started adjuvant hormonal treatment. Patients may already have initiated endocrine therapy at the time of randomization, but randomization must take place within 12 months of date of histological diagnosis and within 6 months of initiating standard adjuvant endocrine therapy. Patients who received neoadjuvant endocrine therapy are eligible as long as they are randomized within 12 months of initial histological diagnosis and after completing no more than 6 months of adjuvant endocrine therapy. Patients may be receiving either tamoxifen or aromatase inhibitor (AI: letrozole, anastrozole, or exemestane). For premenopausal patients and men, concurrent LHRH agonist use is allowable and may also be ongoing at the time of randomization. If a LHRH agonist was used for ovarian protection during neo/adjuvant chemotherapy it is allowable and shall not be taken into account for calculations regarding the 6 months standard adjuvant endocrine therapy."}
• {"criterion_text":"- (15) Absolute neutrophil count ≥ 1,500/mm3"}
• {"criterion_text":"- (16) Platelets ≥ 100,000/ mm3"}
• {"criterion_text":"- (17) Hemoglobin ≥ 10g/dL"}
• {"criterion_text":"- (18) Total serum bilirubin ≤ ULN; or total bilirubin ≤ 3.0 × ULN with direct bilirubin within normal range in patients with documented Gilbert's Syndrome."}
• {"criterion_text":"- (19) Aspartate amino transferase (AST or SGOT) and alanine amino transferase (ALT or SGPT) ≤ 1.5 × institutional ULN."}
• {"criterion_text":"- (2) Age ≥18 years (or per national guidelines)."}
• {"criterion_text":"- (20) Serum creatinine below the upper limit of the institutional normal range (ULN) or creatinine clearance (or glomerular filtration rate [GFR]) ≥ 60 mL/min/1.73 m2 for patients with serum creatinine levels above institutional ULN."}
• {"criterion_text":"- (3) Premenopausal and postmenopausal women or men with Stage II (Stage IIA limited to a max. of 1000 patients) or Stage III early invasive breast cancer per AJCC Breast Cancer Staging version 7 /UICC . Baseline staging to document absence of metastatic disease is not required, however is recommended as determined by institutional practice."}
• {"criterion_text":"- (4) Patients with multicentric and/or multifocal and/or bilateral early invasive breast cancer whose histopathologically examined tumors all meet pathologic criteria for ER+ and/or PR+ and HER2-."}
• {"criterion_text":"- (5) Patients must have histologically confirmed hormone receptor positive (ER+ and/or PR+), HER2-, early invasive breast cancer. ER, PR and HER2 measurements should be performed acc. to institutional guidelines, in a CLIA-approved setting in the US or certified laboratories for Non-US regions. Cut-off values for positive/negative staining should be in accordance with current ASCO/CAP guidelines. Patients with equivocal HER2 in situ hybridization results according to current ASCO/CAP guidelines are eligible, as long as they have not received and are not scheduled to receive anti-HER2 treatment. Testing may occur on diagnostic core or surgical tumor tissue."}
• {"criterion_text":"- (6) Patients must have undergone adequate (definitive) breast surgery for the current malignancy."}
• {"criterion_text":"- (7) A formalin-fixed paraffin-embedded (FFPE) tumor tissue block must be transmitted to a central sample repository and confirmation of receipt must be available prior to randomization."}
• {"criterion_text":"- (8) ECOG performance status 0-1."}
• {"criterion_text":"- (9) Patients must be able and willing to swallow and retain oral medication without a condition that would interfere with enteric absorption."}

Exclusion criteria

• {"criterion_text":"- (1) Concurrent therapy with other Investigational Products."}
• {"criterion_text":"- (10) Patients on antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions or increased immunosuppression with palbociclib."}
• {"criterion_text":"- (11) Patients with clinically significant history of chronic liver disease, including chronic/active viral or other known hepatitis, current alcohol abuse, or cirrhosis, etc."}
• {"criterion_text":"- (12) Patients receiving concurrent exogenous hormone therapy (hormone replacement therapy, oral or any other hormonal contraceptives such as hormonal contraceptive coil, etc.) are not eligible but topical vaginal estrogen therapy is allowable."}
• {"criterion_text":"- (2) Prior therapy with any CDK inhibitor."}
• {"criterion_text":"- (3) Patients with Stage I or IV breast cancer are not eligible. Baseline staging to document absence of metastatic disease is not required, however is recommended as determined by institutional practice."}
• {"criterion_text":"- (4) History of allergic reactions attributed to compounds of chemical or biologic composition similar to palbociclib."}
• {"criterion_text":"- (5) Patients receiving any medications or substances that are potent inhibitors or inducers of CYP3A isoenzymes within 7 days of randomization."}
• {"criterion_text":"- (6) Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, diabetes, or psychiatric illness/social situations that would limit compliance with study requirements. Ability to comply with study requirements is to be assessed by each investigator at the time of screening for study participation."}
• {"criterion_text":"- (7) Pregnant women, or women of childbearing potential without a negative pregnancy test (serum or urine) within 7 days prior to randomization, irrespective of the method of contraception used, are excluded from this study because the effect of palbociclib on a developing fetus is unknown. Breastfeeding must be discontinued prior to study entry."}
• {"criterion_text":"- (8) Patients with a history of any malignancy are ineligible except for the following circumstances: • Patients with a malignancy history other than invasive breast cancer are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. • Patients with the following cancers are eligible, even if diagnosed and treated within the past 5 years: ductal carcinoma in situ of the breast, cervical cancer in situ, and non-metastatic non-melanomatous skin cancer."}
• {"criterion_text":"- (9) Patients are not eligible if they have previously received endocrine therapy within 5 years prior to diagnosis of the current malignancy. This includes use for prophylactic reasons, including treatment of osteoporosis or cancer prevention with tamoxifen, raloxifene or AI. Patients may concurrently receive bisphosphonates or rank ligand inhibitors while on this study if necessary for treatment or prevention of osteopenia or osteoporosis."}

Primary endpoints

• {"endpoint_text":"- Invasive disease-free survival (iDFS) defined acc. to STEEP criteria","definition_or_measurement_approach":"Defined according to STEEP criteria (iDFS as per STEEP)."}

Secondary endpoints

• {"endpoint_text":"- (1) Invasive disease-free survival (iDFS) excl. second primary invasive cancers of non-breast origin as an event.","definition_or_measurement_approach":"iDFS with exclusion of second primary invasive cancers of non-breast origin (i.e., these events are excluded from the iDFS event definition)."}
• {"endpoint_text":"- (2) Overall Survival (OS)","definition_or_measurement_approach":"Overall survival (time to death from any cause)."}
• {"endpoint_text":"- (3) Locoregional recurrences-free survival (LRRFS) defined as the composite of local/regional ipsilateral recurrence, contralateral invasive breast cancer or death from any cause","definition_or_measurement_approach":"LRRFS defined as composite of local/regional ipsilateral recurrence, contralateral invasive breast cancer, or death from any cause."}
• {"endpoint_text":"- (4) Distant recurrence free survival (DRFS) is defined acc. to STEEP criteria as the composite of distant recurrence or death from any cause.","definition_or_measurement_approach":"DRFS per STEEP: composite of distant recurrence or death from any cause."}
• {"endpoint_text":"- (5) Adverse Events","definition_or_measurement_approach":"Safety assessed by adverse events reporting (AE collection)."}

Primary sponsor

Full Name

ABCSG GmbH

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

Austria

Contract research organisations

Name

Almac Clinical Services LLC

Responsibilities

Sponsor duties code: 14 (as listed); contact jacqueline.masker@almacgroup.com

Name

Syneos Health UK Limited

Responsibilities

Sponsor duties codes: 1,12,2,5,8 (as listed); operational/support responsibilities; contact larry.tam@syneoshealth.com

Third parties

• {"country":"United States","full_name":"Pfizer Inc.","duties_or_roles":"codes: 10,12,13,14,5,8,9 (as listed in sponsorDuties); contact Prash.Gopalakrishna@pfizer.com","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Almac Clinical Services LLC","duties_or_roles":"codes: 14 (as listed in sponsorDuties); contact jacqueline.masker@almacgroup.com","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"BioKryo GmbH","duties_or_roles":"value: \"GBG Biobank storage; frozen samples\"","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"Breast International Group","duties_or_roles":"values: \"Supporting trial and protocol\"; codes: 2,5 (as listed)","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Germany","full_name":"Philipps-Universitaet Marburg","duties_or_roles":"value: \"GBG Biobank storage; FFPE samples\"","organisation_type":"Educational Institution"}
• {"country":"United Kingdom","full_name":"Syneos Health UK Limited","duties_or_roles":"codes: 1,12,2,5,8 (as listed in sponsorDuties); contact larry.tam@syneoshealth.com","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Oracle Corp.","duties_or_roles":"code: 3 (as listed); contact marquita.harris@oracle.com","organisation_type":"Non-Pharmaceutical company"}

Co-sponsors

• Alliance Foundation Trials LLC