Letrozole and CDK 4/6 Inhibitor for ER Positive, HER2 Negative Breast Cancer in Postmenopausal Women

Phase II Neoadjuvant Study of Letrozole in Combination With PD0332991 (Oral CDK 4/6 Inhibitor) for ER Positive, HER2 Negative Breast Cancer in Postmenopausal Women

This is a phase II study evaluating the efficacy and safety of the pre-operative use of letrozole plus PD 0332991 (combination therapy)

Study Overview

• Status: Unknown
• Conditions: ER Positive, HER2 Negative Breast Cancer
• Intervention / Treatment: Drug: Letrozole, PD 0332991

• Study Type: Interventional
• Enrollment (Anticipated): 45
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Hong Kong, China
    • Recruiting
    • UNIMED Medical Institute
    • Principal Investigator: Louis Chow, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Postmenopausal women
• Primary tumor greater than 2 cm in diameter
• Histologically proven invasive breast cancer
• Positive estrogen receptor
• Negative HER-2 receptor
• ECOG performance status ≤ 1 or Karnofsky performance status ≥ 70%
• Laboratory values must be follows:

Absolute neutrophil count ≥ 1,500/mm3; Platelets ≥ 100,000/mm3; Hemoglobin ≥ 9 g/dL; Bilirubin ≤ 1.5 × institutional upper limit of normal (ULN); Serum Creatinine ≤ 1.5 × ULN; Alkaline phosphatase ≤ 2 × ULN; AST and ALT ≤ 2 × ULN; Normal finding of ECG - QTc ≤ 470 msec (based on the mean value of the triplicate ECGs); Left ventricular ejection fraction (LVEF) ≥ 60%.

• Able to give written informed consent form
• Able to follow prescription instructions reasonably well

Exclusion Criteria:

• Male
• Severe psychiatric disorder
• Prior history of other malignancy within 5 years of study entry, aside from basal cell carcinoma or the skin or carcinoma-in-situ of the uterine cervix
• Locally advanced breast cancer (T3N1 or Any T4 or Any N2, N3), or distant metastasis
• Multifocal or multicentric breast cancer except that the largest lesion is greater than 2cm
• Major surgery within 3 weeks of first study treatment
• Current use or anticipated need for:

Food or drugs that are known strong CYP3A4 inhibitors; drugs that are known strong CYP3A4 inducers

• Severe cardiovascular diseases in the previous 6 months
• Active inflammatory bowel disease or chronic diarrhea
• Renal Impairment
• Poor adrenal function
• Hepatitis B and/or hepatitis C carriers (unless with normal hepatic function)
• Known human immunodeficiency virus infection
• Known hypersensitivity to anti-aromatase drugs or any cell cycle inhibitor
• Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Letrozole plus PD 0332991; Drug: Letrozole 2.5mg/d for 16 weeks before surgery plus PD 0332991 (CDK-4/6 inhibitor) 125 mg/d for 3 out of 4 weeks in repeated cycles for 16 weeks before surgery	Drug: Letrozole, PD 0332991

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Objective response rates	Every 4 weeks before surgery

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants with Adverse Events	Continuous during the study, up to 28 days after the last treatment

Other Outcome Measures

Outcome Measure	Time Frame
Pathologic response rates	At time of definitive surgery

Collaborators and Investigators

• Sponsor: Organisation for Oncology and Translational Research

Study record dates

Study Major Dates

• Study Start: February 1, 2012

Study Registration Dates

• First Submitted: October 15, 2012
• First Submitted That Met QC Criteria: October 16, 2012
• First Posted (Estimate): October 18, 2012

Study Record Updates

• Last Update Posted (Estimate): December 31, 2013
• Last Update Submitted That Met QC Criteria: December 29, 2013
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Protein Kinase Inhibitors; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Letrozole; Palbociclib
• Other Study ID Numbers: OOTR-N007/LET-CDK