Two Different Schedules of Palbociclib + Second Line Endocrine Therapy in Estrogen Receptor Positive, HER2 Neg Advanced/Metastatic Breast Cancer

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

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Palbociclib 100mg; Drug: Fulvestrant or Tamoxifen or Aromatase Inhibitor; Drug: Palbociclib 125mg

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.

• Study Type: Interventional
• Enrollment (Actual): 180
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • British Columbia
    • Abbotsford British Columbia, British Columbia, Canada, V2S 0C2
      • BCCA - Abbotsford Centre
    • Surrey, British Columbia, Canada, V3V 1Z2
      • BCCA - Fraser Valley Cancer Centre
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BCCA - Vancouver Cancer Centre
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 6Z8
      • The Moncton Hospital
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1B 3V6
      • Dr. H. Bliss Murphy Cancer Centre
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • QEII Health Sciences Centre
  • Ontario
    • Barrie, Ontario, Canada, L4M 6M2
      • Royal Victoria Regional Health Centre
    • Hamilton, Ontario, Canada, L8V 5C2
      • Juravinski Cancer Centre at Hamilton Health Sciences
    • Kingston, Ontario, Canada, K7L 5P9
      • Cancer Centre of Southeastern Ontario at Kingston
    • Newmarket, Ontario, Canada, L3Y 2P9
      • Stronach Regional Health Centre at Southlake
    • Oshawa, Ontario, Canada, L1G 2B9
      • Lakeridge Health Oshawa
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hospital Research Institute
    • St. Catharines, Ontario, Canada, L2S 0A9
      • Niagara Health System
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network
    • Windsor, Ontario, Canada, N8W 2X3
      • Windsor Regional Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada, H4J 1C5
      • Hopital Du Sacre-Coeur de Montreal
    • Montreal, Quebec, Canada, H2L 4M1
      • CHUM - Hopital Notre-Dame
    • Montreal, Quebec, Canada, H3T 1E2
      • The Jewish General Hospital
    • Québec, Quebec, Canada, G1S 4L8
      • CHA-Hopital Du St-Sacrement
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Centre Hospitalier Universitaire de Sherbrooke
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Allan Blair Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Palbociclib (100mg); Palbociclib 100mg PO daily plus Fulvestrant or Tamoxifen or another Aromatase Inhibitor at the standard doses/schedules	Drug: Palbociclib 100mg; 100mg PO daily; Drug: Fulvestrant or Tamoxifen or Aromatase Inhibitor; given at the standard doses/schedules
Active Comparator: Palbociclib (125mg); Palbociclib 125mg PO daily 3 out of 4 weeks plus Fulvestrant or Tamoxifen or another Aromatase Inhibitor at the standard doses/schedules	Drug: Fulvestrant or Tamoxifen or Aromatase Inhibitor; given at the standard doses/schedules; Drug: Palbociclib 125mg; 125mg PO daily 3 weeks out of 4

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival Using the RECIST 1.1 Criteria	progression free survival (PFS) is defined as time from randomization to progression or death from any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Response or No Response	Response rate = Number of (Complete response + partial response) / total treated patients. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.	2 years
Duration of Response	For patients with complete or partial response, duration of response is defined as days from first recorded response to the first date of recurrent or progression or death.	2 years
Overall Survival	Time from randomization to death of any cause.	2 years

Collaborators and Investigators

• Sponsor: Canadian Cancer Trials Group
• Collaborators: Pfizer
• Investigators: Study Chair: Anil A. Joy, Cross Cancer Institute, Edmonton Alberta Canada

Publications and helpful links

General Publications

• Joy AA, Cheng N, Gelmon KA, Mates M, Desbiens C, Clemons M, Taylor S, Lemieux J, DeLuca A, Gasparini L, Lungu I, Soave D, Fortuna A, Pugh T, Liu SS, Bartlett JMS, Awadalla P, Spears M, Chen BE, Bayani J, Parulekar WR. Continuous versus Standard Palbociclib Treatment and Molecular Profiling of Solid Tissues and Liquid Biopsies in the CCTG MA.38 Trial in Advanced Breast Cancer. Cancer Res Commun. 2025 Nov 1;5(11):1998-2011. doi: 10.1158/2767-9764.CRC-25-0346.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2016
• Primary Completion (Actual): August 15, 2018
• Study Completion (Actual): November 29, 2023

Study Registration Dates

• First Submitted: December 11, 2015
• First Submitted That Met QC Criteria: December 11, 2015
• First Posted (Estimated): December 15, 2015

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: March 23, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Enzyme Inhibitors; Steroid Synthesis Inhibitors; Hormone Antagonists; Estrogen Antagonists; Organic Chemicals; Pharmacologic Actions; Chemical Actions and Uses; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Benzene Derivatives; Estradiol; Estrenes; Estranes; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Stilbenes; Benzylidene Compounds; Fulvestrant; Tamoxifen; Aromatase Inhibitors; palbociclib
• Other Study ID Numbers: MA38

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: As per CCTG policy.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No