Preoperative Window of Endocrine Therapy Provides Information to Increase Compliance (POWER PIINC)

• ClinicalTrials.gov Identifier: NCT01614210
• Recruitment Status: Completed
• First Posted: June 7, 2012
• Results First Posted: December 13, 2017
• Last Update Posted: August 1, 2018
• Sponsor: University of Utah
• Information provided by (Responsible Party): University of Utah

Study Description

Brief Summary:

The purpose of the study is to see if tumors respond to endocrine therapy by taking a total of 21 doses of Tamoxifen before and after surgery. Tamoxifen is currently approved by the FDA (Food and Drug Administration) for use in the treatment of hormone positive breast cancer.

Condition or disease	Intervention/treatment	Phase
Newly Diagnosed Hormone Positive Clinical Stage 1 or 2 Breast Cancer	Drug: Tamoxifen; Procedure: Breast cancer surgery	Phase 2

Detailed Description:

Patients who are eligible (newly diagnosed hormone positive clinical stage 1 or 2 breast cancer) will be approached about the study. If they sign informed consent a prescription for 21 doses of Tamoxifen will be provided. The patient's surgery will be scheduled at a time convenient for the patient and the surgeon. Once the surgery has been scheduled, a medication calendar will be completed that allows the patient to take tamoxifen for 7 days preoperatively with the 7th dose of tamoxifen to coincide with the day before surgery. The patient will continue to take tamoxifen for 2 weeks (14 days) after surgery. Patients will then proceed along normal treatment guidelines. For those needing chemotherapy or radiation therapy, we recommend the long term endocrine therapy start at the conclusion of chemo and/or radiation treatments. For those not going on to any additional therapy, the prescription for endocrine therapy will be written at the initial post-operative visit.

Unstained slides from the formalin-fixed, paraffin-embedded tissue blocks from the patient's breast tissue from which the original diagnosis of breast cancer was made by H&E will be stained for Ki67. After endocrine therapy and subsequent resection, carcinoma will be confirmed by the participating pathologist on H&E, and Ki67 will be performed on unstained slides from a representative tissue block containing invasive carcinoma. The pathologist will circle a designated area of tumor on the H&E slide and both the H&E and immunostained (Ki67) slides will be scanned in a digital imaging device (Aperio XT Scanscope), which quantitatively analyzes the tumor designated by the pathologist with image analysis algorithms. The algorithm accurately detects regions of interest and distinguishes cells and sub-cellular objects within these target regions. It determines morphology and expression profiles per individual cell or cell compartment. For Ki67 analysis, a nuclear Immunohistochemistry (IHC) algorithm will be used.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 52 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Preoperative Window of Endocrine Therapy Provides Information to Increase Compliance
• Study Start Date: August 2012
• Actual Primary Completion Date: November 2016
• Actual Study Completion Date: November 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: All patients; All patients enrolled in the study.	Drug: Tamoxifen; All patients will take tamoxifen 20 mg po daily for 7 days prior to surgery and for 14 days after surgery.; Procedure: Breast cancer surgery; Breast cancer surgery

Outcome Measures

Primary Outcome Measures :

1. Change in Ki67 Expression in Tumors [ Time Frame: 7 days ]
   Demonstrate a significant change in Ki67 expression in tumors with 7 days of pre-surgical tamoxifen.

Secondary Outcome Measures :

1. Change in FACT-ES Symptom Scores [ Time Frame: 18 months ]
   Patients were given the Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES) quality of life assessment at baseline (prior to tamoxifen administration) and again 18 months following breast surgery to assess quality of life. The difference in total score from baseline to 18 months was calculated. The FACT-ES total score ranges from 0-180, with higher scores indicating higher quality of life.
2. Number of Participants With Long Term Endocrine Therapy Adherence [ Time Frame: 18 months ]
   For the patient population on this study, endocrine therapy was indicated for 5 years post-surgery according to the current standard of care recommendations for hormone positive breast cancer. Endocrine therapy was prescribed as standard of care as appropriate for each patient's situation. At 18 months post-surgery, patients were evaluated to determine if they were taking their endocrine therapy as prescribed.
3. Correlation Between Changes in Ki67 and Symptoms [ Time Frame: 7 days ]
   Evaluate correlation between changes in Ki67 expression and symptom scores. Differences between changes in FACT-ES total score were correlated with changes in Ki67 expression using a the Spearman correlation method and results are expressed as the correlation coefficient.

Other Outcome Measures:

1. Change in FACT-ES Symptom Scores [ Time Frame: 7 days ]
   Patients were given the Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES) quality of life assessment at baseline (prior to tamoxifen administration) and again 7 days following start of tamoxifen to assess quality of life while on tamoxifen. The difference in total score from baseline to 7 days was calculated. The FACT-ES total score ranges from 0-180, with higher scores indicating higher quality of life.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Age > 18 years old
• Diagnosed with hormone receptor positive invasive breast cancer (estrogen receptor (ER) or progesterone receptor (PR) or both >1%) by core needle biopsy
• Clinical American Joint Committee on Cancer (AJCC) 7th edition Stage 1 or 2
• Candidate for surgical therapy
• Eastern Cooperative Oncology Group (ECOG) performance status 0,1, or 2
• No chemotherapy or endocrine therapy for breast cancer in last 5 years
• Paraffin fixed core needle tissue block, or biopsy punch available for central analysis for proliferative markers
• Not pregnant or lactating and practicing adequate birth control if premenopausal
• Able and willing to provide informed consent

Exclusion Criteria:

• Prior personal history of uterine cancer
• Prior personal history of stroke or deep vein thrombosis (DVT)
• Current therapy with strong CYP2D6 inhibitors The following medications should not be administered with tamoxifen (21 day treatment period) and will need to be stopped for the designated period of time prior to starting the study tamoxifen.

No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage 0, I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years

Fluoxetine - should be discontinued 30 days prior to starting tamoxifen Paroxetine - should be discontinued 5 days prior to starting tamoxifen Sertraline - should be discontinued 5 days prior to starting tamoxifen Bupropion - should be discontinued 5 days prior to starting tamoxifen

• Concurrent coumarin-type anticoagulation therapy
• Any other contraindications to tamoxifen therapy

Contacts and Locations

Locations

United States, Utah

Huntsman Cancer Institute

Salt Lake City, Utah, United States, 84112

Sponsors and Collaborators

University of Utah

Investigators

• Principal Investigator: Leigh Neumayer, MD; Huntsman Cancer Institute

More Information

• Responsible Party: University of Utah
• ClinicalTrials.gov Identifier: NCT01614210
• Other Study ID Numbers: HCI57098
• First Posted: June 7, 2012
• Results First Posted: December 13, 2017
• Last Update Posted: August 1, 2018
• Last Verified: July 2018

Additional relevant MeSH terms:

Tamoxifen; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Bone Density Conservation Agents