Clinical trial NCT02630693: Two Different Schedules of Palbociclib + Second Line Endocrine Therapy in Estrogen Receptor Positive, HER2 Neg Advanced/Metastatic Breast Cancer
Official title: Randomized Phase II Study Comparing Two Different Schedules of Palbociclib Plus Second Line Endocrine Therapy in Women With Estrogen Receptor Positive, HER2 Negative Advanced/Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Lead sponsor: Canadian Cancer Trials Group
Sponsor class: NETWORK
Collaborators: name: Pfizer
First posted: 2015-12-15
Enrollment: 180
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if the combination of endocrine therapy and Palbociclib at a daily dose of 100 mg will result in a better response to therapy with fewer dose interruptions than the proposed dosing regimen of 125 mg daily for 21 days out of a 28 day cycle in combination with endocrine therapy.

Detailed description: The standard or usual treatment of this type of breast cancer is endocrine therapy. Palbociclib is a new type of drug for breast cancer. Laboratory tests as well as studies in animals and people show that it may help slow the growth of breast cancer. The most widely tested regimen of Palbociclib for patients with metastatic/advanced breast cancer is 125 mg every day for 21 days out of a 28 day cycle in combination with standard endocrine (hormone) therapy. This study explores if administering a lower dose of palbociclib - 100 mg given every day of a 28 day cycle in combination with standard endocrine (hormone) therapy - may result in more tumour shrinkage and be better tolerated.

Eligibility criteria: Inclusion Criteria:

* Premenopausal and postmenopausal women 18 years of age or older.
* Histologically confirmed adenocarcinoma of the breast, with ER positive and HER2 negative status based on local testing on most recent pathological tumour specimen.
* Patients must satisfy the following criteria for prior therapy:

  * Progressed during treatment or within 12 months of completion of adjuvant endocrine therapy or
  * Progressed during prior endocrine therapy for advanced/metastatic disease. Note: 'Progressed during endocrine therapy' means that the patient progressed while on or within 1 month after discontinuation of endocrine therapy.
* One line of chemotherapy for advanced/metastatic disease (regardless of prior adjuvant chemotherapy use) is allowed in addition to endocrine therapy.
* Patients must have evidence of disease to be eligible for the study, but measurable disease is not mandatory.
* For those patient with measureable disease who will be included in the response assessment, the following criteria must apply:

  * X-ray ≥ 20 mm
  * Spiral CT scan or physical exam ≥ 10 mm (lymph nodes must be ≥ 15 mm in the short axis)
  * Conventional CT scan, MRI ≥ 20 mm
  * Measurable lesions must be outside a previous radiotherapy field if they are the sole site of disease, unless disease progression has been documented.

Tumor lesions previously irradiated or subjected to other loco regional therapy will only be deemed measurable if progression at the treated site after completion of therapy is clearly documented.

* Eastern Cooperative Oncology Group (ECOG) 0-2.
* Adequate organ and bone marrow function as defined by:

  * ANC ≥ 1,500/mm3 (1.5 x 109/L)
  * Platelets ≥ 100,000/mm3 (100 x 109/L)
  * Serum creatinine ≤ 1.5 x ULN or estimated creatinine clearance ≥60 ml/min as calculated using the method standard for the institution;
  * Total serum bilirubin ≤ 1.5 x ULN (\<3 ULN if Gilbert's disease).
* Patient must agree to provide tumour tissue from the most recent pathological tumour specimen.
* Patient is able (i.e. sufficiently fluent) and willing to complete the quality of life questionnaires in either English or French
* Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate
* Patients must be accessible for treatment and follow up. Patients registered on this trial must be treated and followed at the participating centre. This implies there must be reasonable geographical limits placed on patients being considered for this trial.
* In accordance with NCIC CTG policy, protocol treatment is to begin within 2 working days of patient randomization.
* Women of childbearing potential must have agreed to use a highly effective contraceptive method.

Exclusion Criteria:

* Patients with advanced, symptomatic, visceral spread that are at risk of life threatening complication in the short term.
* Patients with symptomatic CNS involvement, meningeal or parenchymal, that is uncontrolled or requires steroids.
* Prior treatment with any CDK 4/6 inhibitor.
* Prior treatment with mTOR inhibitors.
* Active second malignancy, regardless of ongoing treatment.
* Any concurrent medical condition that in the opinion of the investigator would interfere with the safe administration of the study drug and participation in the study.
* Participation in a prior anti-cancer investigational study within 30 days prior to enrollment.

Primary outcomes:
measure: Progression Free Survival Using the RECIST 1.1 Criteria
timeFrame: 2 years
Secondary outcomes:
measure: Number of Participants With Response or No Response
timeFrame: 2 years
measure: Duration of Response
timeFrame: 2 years
measure: Overall Survival
timeFrame: 2 years
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Abbotsford
country: Canada
facility: BCCA - Abbotsford Centre
state: British Columbia
city: Surrey
country: Canada
facility: BCCA - Fraser Valley Cancer Centre
state: British Columbia
city: Vancouver
country: Canada
facility: BCCA - Vancouver Cancer Centre
state: British Columbia
city: Moncton
country: Canada
facility: The Moncton Hospital
state: New Brunswick
city: St. John's
country: Canada
facility: Dr. H. Bliss Murphy Cancer Centre
state: Newfoundland and Labrador
city: Halifax
country: Canada
facility: QEII Health Sciences Centre
state: Nova Scotia
city: Barrie
country: Canada
facility: Royal Victoria Regional Health Centre
state: Ontario
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre at Hamilton Health Sciences
state: Ontario
city: Kingston
country: Canada
facility: Cancer Centre of Southeastern Ontario at Kingston
state: Ontario
city: Newmarket
country: Canada
facility: Stronach Regional Health Centre at Southlake
state: Ontario
city: Oshawa
country: Canada
facility: Lakeridge Health Oshawa
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital Research Institute
state: Ontario
city: St. Catharines
country: Canada
facility: Niagara Health System
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Windsor
country: Canada
facility: Windsor Regional Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: CHUM - Hopital Notre-Dame
state: Quebec
city: Montreal
country: Canada
facility: The Jewish General Hospital
state: Quebec
city: Montreal
country: Canada
facility: Hopital du Sacre-Coeur de Montreal
state: Quebec
city: Quebec City
country: Canada
facility: CHA-Hopital Du St-Sacrement
state: Quebec
city: Sherbrooke
country: Canada
facility: Centre hospitalier universitaire de Sherbrooke
state: Quebec
city: Regina
country: Canada
facility: Allan Blair Cancer Centre
state: Saskatchewan
Study officials:
affiliation: Cross Cancer Institute, Edmonton Alberta Canada
name: Anil A. Joy
role: STUDY_CHAIR
References: