Exemestane With Sunitinib (SUTENT®) in Metastatic Breast Cancer (EXTENT)

EXTENT: Exemestane (AROMASIN®) in Combination With Sunitinib (SUTENT®) in Hormone Receptor Positive Metastatic Breast Cancer

The investigators want to find out if the treatments used in this study are helpful to patients that are diagnosed with hormone receptor positive metastatic breast cancer. The investigators want to also look at any side effects that could happen while patients are on the study treatments. The investigators want to see if there are any changes that could show us if your cancer is responding to the study treatments.

Study Overview

• Status: Terminated
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: Exemestane; Drug: Sutent

Detailed Description

The study design is a phase II design. Eligible patients will undergo staging work up and start treatment. Every 28-day period (4 weeks) will count as a cycle. Medical evaluations will be performed every 4 weeks and staging work up will be repeated every 12 weeks.

The primary objective of the study is to assess progression free survival (PFS) of treatment with exemestane and sunitinib in post¬menopausal subjects with hormone receptor positive (ER-positive and/or PR-positive) unresectable locally advanced or metastatic breast cancer subjects who have progressed on prior hormonal treatment.

In addition we want to:

1. Obtain assessments of overall response rate (ORR), clinical benefit rate (CBR), and overall survival (OS).
2. Determine the safety and tolerability of the combination regimen.
3. Study molecular changes in tissue biopsies, circulating tumor cells (CTCs), and circulating endothelial cells (CECs), and explore associations with treatment response and resistance.

1. Blood samples will be drawn for enumeration and profiling of circulating tumor cells and circulating endothelial cells at study entry (prior to starting study medications), four weeks after starting study medications, twelve weeks after starting study medications and at disease progression. These samples will be strongly encouraged but the patients may decline any or all of them without impacting their eligibility or continuation on the study.

2. If the patient participating on the study has an easily accessible breast mass or metastatic lesion (e.g. lymphadenopathy, skin metastasis, chest wall metastasis), a core needle or punch biopsy will be obtained at study entry (prior to starting study medications), four weeks after starting study medications, and at disease progression. These biopsies will be strongly encouraged but the patients may decline any or all of them without impacting their eligibility or continuation on the study.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine, Lester and Sue Smith Breast Center

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:

1. Must have metastatic breast cancer or locally advanced not amenable to curative therapy.
2. Measurable or evaluable disease are eligible.
3. Tumors must be Estrogen Receptor (ER)-positive and/or Progesterone Receptor (PR)-positive.
4. Human Epidermal Growth Factor Recepter 2 (HER2)-positive tumors are allowed but must have failed Herceptin therapy.
5. Postmenopausal
6. No more than 3 lines of chemotherapy
7. No more than 3 lines of hormonal therapy
8. Bisphosphonates may be given according to their product license
9. Left ventricular ejection fraction within institutional normal limits
10. Liver function and kidney function tests within the upper limit of normal. In patients with liver metastasis, liver function tests should be < 5 times the upper limit of normal.
11. Adequate blood counts
12. Normal thyroid function tests.
13. Patients with Central Nervous System (CNS) metastatic disease are allowed if the disease is stable for more than 3 months by CT or MRI.
14. Adequate general health (Eastern Cooperative Oncology Group (ECOG) performance status 0-2).
15. Able to give informed consent and follow the procedures of the study.

Exclusion Criteria:

1. Patients previously treated with exemestane in any setting.
2. Patients previously treated with sunitinib.
3. Patients with cardiac dysfunction or active cardiac disease
4. Patients with uncontrolled CNS metastasis.
5. Poorly controlled hypertension
6. Blood counts or liver and kidney tests that fall outside the ranges outlined in inclusion criteria 9-10 above.
7. ECOG performance status 3 or 4.
8. History of other malignancy within the last 5 years, except for carcinoma in situ of the cervix or basal cell carcinoma of the skin.
9. History of a cerebrovascular accident, non-catheter related deep vein thrombosis, or pulmonary embolism in the last 5 years.
10. Major surgical procedure or significant traumatic injury within 28 days prior to study entry.
11. Premenopausal status.
12. History of receiving any investigational treatment within 28 days of study medication initiation.
13. Current known infection.
14. Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease; wound healing disorders; ulcers; or bone fractures).
15. Medical or psychiatric condition that in the opinion of the principal investigator impair their ability to participate in the 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: Exemestane plus Sutent; All patients enrolled on the study will receive treatment as follows: Exemestane 25 mg by mouth every day.; Sunitinib 37.5 mg by mouth every day.	Drug: Exemestane; Exemestane 25 mg by mouth every day.; Other Names: Aromasin; Drug: Sutent; Sunitinib 37.5 mg by mouth every day.; Other Names: (Sunitinib)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Disease Progression in Weeks	Time from the first day of treatment to date of progression in weeks	Medical evaluation every 4 weeks;The study does not have a fixed time frame for each participant. Duration of therapy depends on individule response, evidence of disease progression and tolerance

Secondary Outcome Measures

Outcome Measure	Time Frame
Obtain Assessments of Overall Response Rate, Clinical Benefit Rate, and Overall Survival	5 years
Determine the Safety and Tolerability	5 years
Study Molecular Changes in Tissue Biopsies, Circulating Tumor Cells, and Circulating Endothelial Cells	5 years

Collaborators and Investigators

• Sponsor: Baylor Breast Care Center
• Collaborators: Pfizer
• Investigators: Principal Investigator: Mothaffar Rimiawi, MD, Baylor College of Medicine

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): February 1, 2012

Study Registration Dates

• First Submitted: May 18, 2009
• First Submitted That Met QC Criteria: May 19, 2009
• First Posted (Estimate): May 20, 2009

Study Record Updates

• Last Update Posted (Actual): July 24, 2020
• Last Update Submitted That Met QC Criteria: July 9, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Breast Cancer; Metastatic; Hormone Receptor Positive
• 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; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Sunitinib; Exemestane
• Other Study ID Numbers: H 24786 / EXTENT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No