PD 0332991 and Anastrozole for Stage 2 or 3 Estrogen Receptor Positive and HER2 Negative Breast Cancer

NCT01723774 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: 201301106
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 4

Brief Summary

A Phase II study to investigate the potential utility of PD 0332991 in the treatment of early stage ER+ Human epidermal growth factor receptor 2 (HER2)- breast cancer, to investigate whether the combination of PD 0332991 and anastrozole is able to: 1) improve the pathologic complete response rate when compared to the historical control of single agent aromatase inhibitors, 2) result in fewer patients with on therapy Ki67\>10% compared to historical control.

Conditions

Breast Neoplasms

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Complete Cell Cycle Arrest at Cycle 1 Day 15 (PIK3CA Wild Type Cohort Only)

  Complete cell cycle arrest is defined as Ki67 ≤ 2.7% following 2 weeks of neoadjuvant PD 0332991

  At cycle 1 day 15 (2 weeks)

• Number of Participants With Complete Cell Cycle Arrest at Cycle 1 Day 15 (Endocrine Resistant Cohort Only)

  Complete cell cycle arrest is defined as Ki67 ≤ 2.7% following 2 weeks of neoadjuvant PD 0332991

  At cycle 1 day 15 (2 weeks)

Secondary Outcomes (17)

• Number of Participants With Complete Cell Cycle Arrest at Cycle 1 Day 15 ( PIK3CA Mutant Type Cohort Only)

  At cycle 1 day 15 (2 weeks)

• Number of Participants With Complete Cell Cycle Arrest

  Cycle 1 day 1 and cycle 1 day 15 (2 weeks)

• Clinical Response Rate

  16 weeks

• Radiologic Response Rate

  At the end of cycle 4 prior to surgery (estimated to be 16 weeks)

• Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events

  From start of treatment through 30 days after completion of an estimated 4 months of neoadjuvant therapy

Study Arms (3)

Arm 1: PIK3CA Wild Type Cohort

EXPERIMENTAL

* Tumor biopsy for testing/research at baseline and Cycle 1 Day 15 * Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days. * Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery) * Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5. * Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.

Drug: PD0332991; Drug: Anastrozole; Drug: Goserelin; Procedure: Surgery (standard of care); Procedure: Tumor biopsy

Arm 2: PIK3CA Mutant Type Cohort

EXPERIMENTAL

* Tumor biopsy for testing/research at baseline and Cycle 1 Day 15 * Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days. * Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery) * Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5. * Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.

Drug: PD0332991; Drug: Anastrozole; Drug: Goserelin; Procedure: Surgery (standard of care); Procedure: Tumor biopsy

Arm 3: Endocrine Resistant Cohort

EXPERIMENTAL

* Tumor biopsy for testing/research at baseline and Cycle 1 Day 15 * Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery) * Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5. * Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.

Drug: PD0332991; Drug: Anastrozole; Drug: Goserelin; Procedure: Surgery (standard of care); Procedure: Tumor biopsy

Interventions

PD0332991 DRUG

Arm 1: PIK3CA Wild Type Cohort; Arm 2: PIK3CA Mutant Type Cohort; Arm 3: Endocrine Resistant Cohort

Anastrozole DRUG

Also known as: Arimidex®

Arm 1: PIK3CA Wild Type Cohort; Arm 2: PIK3CA Mutant Type Cohort; Arm 3: Endocrine Resistant Cohort

Goserelin DRUG

Also known as: Zoladex®, Decapeptide I

Arm 1: PIK3CA Wild Type Cohort; Arm 2: PIK3CA Mutant Type Cohort; Arm 3: Endocrine Resistant Cohort

Surgery (standard of care) PROCEDURE

-Breast and axillary lymph node surgery

Arm 1: PIK3CA Wild Type Cohort; Arm 2: PIK3CA Mutant Type Cohort; Arm 3: Endocrine Resistant Cohort

Tumor biopsy PROCEDURE

Arm 1: PIK3CA Wild Type Cohort; Arm 2: PIK3CA Mutant Type Cohort; Arm 3: Endocrine Resistant Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Prior treatment of this cancer including: surgery, radiation, chemotherapy, biotherapy, hormonal therapy, investigational agent prior to study entry
• Receiving any investigational agents
• Prior therapy with any Cdk4 inhibitor
• Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism
• Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled symptomatic cardiac arrhythmia, psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant/nursing
• Unwilling to employ adequate contraception
• Known HIV-positive on combination antiretroviral therapy
• Evidence of inflammatory cancer
• Known metastatic disease
• Current use of anticoagulation therapy
• Previous excisional biopsy of the breast cancer or sentinel lymph node biopsy
• Any condition that impairs patient's ability to swallow PD 0332991 tablets (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption)
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to PD 0332991 or other agents used in the study
• Corrected QT interval \>470 msec

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Pfizer: collaborator

Study Sites (4)

University of Alabama

Birmingham, Alabama, 35233, United States

Location

Mayo Clinic - Scottsdale

Scottsdale, Arizona, 85259, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63122, United States

Location

Related Publications (1)

• Bagegni N, Thomas S, Liu N, Luo J, Hoog J, Northfelt DW, Goetz MP, Forero A, Bergqvist M, Karen J, Neumuller M, Suh EM, Guo Z, Vij K, Sanati S, Ellis M, Ma CX. Serum thymidine kinase 1 activity as a pharmacodynamic marker of cyclin-dependent kinase 4/6 inhibition in patients with early-stage breast cancer receiving neoadjuvant palbociclib. Breast Cancer Res. 2017 Nov 21;19(1):123. doi: 10.1186/s13058-017-0913-7.

  PMID: 29162134 DERIVED

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Breast Neoplasms

Interventions

palbociclib; Anastrozole; Goserelin; Surgical Procedures, Operative; Standard of Care

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Cynthia X. Ma, M.D., Ph.D.
• Organization: Washington University School of Medicine

cynthiaxma@wustl.edu

314-362-9383

Study Officials

• Cynthia X Ma, M.D., Ph.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2012
• First Posted: November 8, 2012
• Study Start: April 10, 2013
• Primary Completion: April 13, 2021
• Study Completion (Estimated): August 24, 2026
• Last Updated: December 9, 2025
• Results First Posted: June 2, 2022

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)