Study Comparing Two Different Schedules of Palbociclib Plus Second Line Endocrine Therapy in Women With Estrogen Receptor Positive, HER2 Negative Advanced/Metastatic Breast Cancer

• Sponsor: Canadian Cancer Trials Group
• Collaborator: Pfizer
• Information provided by (Responsible Party): Canadian Cancer Trials Group

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Breast Cancer	Drug: Palbociclib 100mg; Drug: Palbociclib 125mg; Drug: Fulvestrant or Tamoxifen or Aromatase Inhibitor	Phase 2

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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	180 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
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
Actual Study Start Date :	December 16, 2015
Actual Primary Completion Date :	August 15, 2018
Estimated Study Completion Date :	February 2019

Arms and Interventions

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: Palbociclib 125mg; 125mg PO daily 3 weeks out of 4; Drug: Fulvestrant or Tamoxifen or Aromatase Inhibitor; given at the standard doses/schedules

Outcome Measures

Primary Outcome Measures :

1. Progression free survival using the RECIST 1.1 criteria [ Time Frame: 2 years ]

Secondary Outcome Measures :

1. Number and severity of adverse events [ Time Frame: 2 years ]
2. Response Rate using the Cochran-Mantel-Haenszel test [ Time Frame: 2 years ]
3. Duration of response using the log-rank test [ Time Frame: 2 years ]
4. Clinical Benefit Rate using the Cochran-Mantel-Haenszel test [ Time Frame: 2 years ]
5. Overall Survival [ Time Frame: 2 years ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	Female
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Locations

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

Sponsors and Collaborators

Canadian Cancer Trials Group

Pfizer

Investigators

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Study Chair:	Anil A. Joy	Cross Cancer Institute, Edmonton Alberta Canada

More Information

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Responsible Party:	Canadian Cancer Trials Group
ClinicalTrials.gov Identifier:	NCT02630693 History of Changes
Other Study ID Numbers:	MA38
First Posted:	December 15, 2015
Last Update Posted:	September 27, 2018
Last Verified:	September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Additional relevant MeSH terms:

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Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Estrogens; Tamoxifen; Fulvestrant; Palbociclib; Aromatase Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs	Estrogen Antagonists; Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Bone Density Conservation Agents; Estrogen Receptor Antagonists; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Steroid Synthesis Inhibitors