Exemestane in Treating Postmenopausal Women With Stage IV Breast Cancer

• Sponsor: City of Hope Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00810797
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 36
• Locations: 2
• Arm: 1
• Duration (Months): 126.8
• Patients Per Site: 18
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using exemestane may fight breast cancer by lowering the amount of estrogen the body makes.

PURPOSE: This phase II trial is studying how well exemestane works in treating postmenopausal women with stage IV breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: exemestane; Other: laboratory biomarker analysis; Procedure: quality-of-life assessment; Other: immunohistochemistry staining method	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Progression-free survival at 4 months, as measured by Response Evaluation Criteria in Solid Tumors (RECIST).

SECONDARY OBJECTIVES:

1. Objective response rate (complete response [CR] and partial response [PR]).

2. Clinical benefit (CR, PR, and stable disease >= 6 months).

3. Assessment of toxicity.

4. Assessment of compliance with medication adherence.

5. Assessment of quality of life.

6. Assessment of bone health.

TERTIARY OBJECTIVES:

1. Serial measurements of serum estradiol, estrone, and estrone sulfate.

2. To investigate treatment resistance (e.g., expression of amphiregulin, epidermal growth factor receptor [EGFR]), using molecular and immunohistochemical analyses of blood and tumor samples of pre- and post- (when available) treatment tissues. Microarray analyses to quantitate the expression of specific estrogen-responsive genes (e.g. thyroid transcription factor 1 [TTF1] and PDZK1) will also be performed.

OUTLINE: Patients receive exemestane orally (PO) once daily (QD) on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed periodically for 1 year.

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Intermittent Exemestane Therapy for Metastatic Breast Cancer
• Study Start Date: Dec 2, 2008
• Actual Primary Completion Date: Jun 26, 2019
• Actual Study Completion Date: Jun 26, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (exemestane) Patients receive oral exemestane once daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Drug: exemestane; Given orally; Other: laboratory biomarker analysis; One year after completion of study treatment; Procedure: quality-of-life assessment; One year after completion of study treatment; Other: immunohistochemistry staining method; Correlative studies; Other Names: immunohistochemistry

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival [Until disease progression of death from any cause, up to 3 years]

   Estimated using the product-limit method of Kaplan and Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Secondary Outcome Measures

1. Overall Response Rate [Until disease progression or off treatment, assessed up to 1 year]

   Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically or cytologically confirmed metastatic carcinoma of the breast

• Hormone receptor (estrogen receptor [ER] and/or progesterone receptor [PR]) positive disease (defined as: ER and/or PR positivity as >= 5% staining), as confirmed by immunohistochemistry (IHC) based on primary breast tissue or metastatic tissue

• Postmenopausal, as defined by any of the following:

• Natural menopause, with at least 1 year since last menses

• Chemotherapy-induced menopause with at least 1 year from last menses and serum luteinizing hormone (LH)/follicle-stimulating hormone (FSH) and estradiol levels within the postmenopausal range

• History of surgical or radiation-induced ovarian ablation

• For women =< 56 years old and with a history of hysterectomy but at least one ovary intact, serum LH/FSH and estradiol levels must be within the postmenopausal range

• Postmenopausal women with disease recurrence while receiving either tamoxifen or a non-steroidal aromatase inhibitor (AI) as adjuvant therapy (as long as adjuvant hormonal therapy was taken for 6 months before disease progression) or with disease recurrence following the discontinuation/completion of adjuvant hormonal therapy

• Postmenopausal women with disease progression following either 0, 1 or 2 prior hormonal therapies for metastatic breast cancer, as long as the subject has had no prior exposure to exemestane (EXE)

• Measurable or non-measurable (but evaluable) disease, as defined by RECIST criteria

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

• Neutrophil count >= 1.5 X 10^9 cells/L

• Platelet count >= 100 X 10^9 cells/L

• Serum creatinine =< 1.5 times upper limit of normal (ULN)

• Total serum bilirubin =< 1.5 times ULN

• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) levels =< 2.5 x ULN in patients without liver metastases or =< 5 times ULN in patients with liver metastases

• Alkaline phosphatase =< 2.5 times the ULN for patients without bone or liver metastases

• Subjects must have an estimated life expectancy of greater than 6 months

Exclusion Criteria:

• Prior exposure to EXE, whether in the adjuvant or metastatic setting

• Prior history of any other cancer with the exception of non-melanoma skin cancer and treated in situ carcinoma of the cervix

• Active or symptomatic central nervous system (CNS) metastasis (stable or treated brain metastasis allowed but patients must be off decadron, if given for CNS disease)

• Hormone-receptor negative or unknown breast cancer

• More than two prior chemotherapy regimen for treatment of metastatic disease (any prior chemotherapy given in the adjuvant setting is permitted)

• Administration of any other anti-cancer therapy within 2 weeks of initiating study treatment; use of bisphosphonates, however, are permitted for patients with known bone metastases

• Treatment with any other concurrent investigational agent or anti-tumor drug (chemotherapy, antibody therapy or other biologic agents), will not be permitted

• Subjects who have had no prior exposure to endocrine therapy

• Any uncontrolled medical co-morbidity or psychiatric disorder which interferes with the ability to provide informed consent or comply with study procedures

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope Medical Center	Duarte	California	United States	91010-3000
2	South Pasadena Cancer Center	South Pasadena	California	United States	91030

Sponsors and Collaborators

• City of Hope Medical Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: George Somlo, MD, City of Hope Medical Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 25, 2013

More Information

Publications

None provided.

• Responsible Party: City of Hope Medical Center
• ClinicalTrials.gov Identifier: NCT00810797
• Other Study ID Numbers: 08063; P30CA033572; CHNMC-08063; CDR0000629864; NCI-2010-00761
• First Posted: Dec 18, 2008
• Last Update Posted: Oct 19, 2020
• Last Verified: Jul 1, 2019

• Keywords provided by City of Hope Medical Center: recurrent breast cancer; stage IV breast cancer
• Additional relevant MeSH terms: Breast Neoplasms; Exemestane

Study Results

Participant Flow

Arm/Group Title	Treatment (Exemestane)
Arm/Group Description	Patients receive 25mg oral exemestane once daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. exemestane: Given orally laboratory biomarker analysis: One year after completion of study treatment quality-of-life assessment: One year after completion of study treatment immunohistochemistry staining method: Correlative studies
Period Title: Overall Study
STARTED	36
COMPLETED	36
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment (Exemestane)
Arm/Group Description	Patients receive 25mg oral exemestane once daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. exemestane: Given orally laboratory biomarker analysis: One year after completion of study treatment quality-of-life assessment: One year after completion of study treatment immunohistochemistry staining method: Correlative studies
Overall Participants	36
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	60
Sex: Female, Male (Count of Participants)
Female	36 100%
Male	0 0%
Race/Ethnicity, Customized (Count of Participants)
Caucasian	13 36.1%
Hispanic	15 41.7%
African American	1 2.8%
Asian	4 11.1%
Other	3 8.3%
Region of Enrollment (participants) [Number]
United States	36 100%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival
Description	Estimated using the product-limit method of Kaplan and Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame	Until disease progression of death from any cause, up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Exemestane)
Arm/Group Description	Patients receive 25mg oral exemestane once daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. exemestane: Given orally laboratory biomarker analysis: One year after completion of study treatment quality-of-life assessment: One year after completion of study treatment immunohistochemistry staining method: Correlative studies
Measure Participants	36
Median (95% Confidence Interval) [months]	4.3

2. Secondary Outcome

Title	Overall Response Rate
Description	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time Frame	Until disease progression or off treatment, assessed up to 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Exemestane)
Arm/Group Description	Patients receive 25mg oral exemestane once daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. exemestane: Given orally laboratory biomarker analysis: One year after completion of study treatment quality-of-life assessment: One year after completion of study treatment immunohistochemistry staining method: Correlative studies
Measure Participants	36
Number (95% Confidence Interval) [percentage of participants]	8.3 23.1%

Adverse Events

Time Frame	Adverse events were collected over a period of 5 years and 8 months.
Adverse Event Reporting Description	"Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Arm/Group Title	Treatment (Exemestane)
Arm/Group Description	Patients receive 25mg oral exemestane once daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. exemestane: Given orally laboratory biomarker analysis: One year after completion of study treatment quality-of-life assessment: One year after completion of study treatment immunohistochemistry staining method: Correlative studies
All Cause Mortality
	Treatment (Exemestane)
	Affected / at Risk (%)	# Events
Total	30/36 (83.3%)
Serious Adverse Events
	Treatment (Exemestane)
	Affected / at Risk (%)	# Events
Total	4/36 (11.1%)
Gastrointestinal disorders
Rectal hemorrhage	1/36 (2.8%)	1
General disorders
Disease progression	1/36 (2.8%)	1
Infections and infestations
Device related infection	1/36 (2.8%)	1
Skin infection	1/36 (2.8%)	2
Vascular disorders
Hypotension	1/36 (2.8%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Exemestane)
	Affected / at Risk (%)	# Events
Total	35/36 (97.2%)
Blood and lymphatic system disorders
Hemoglobin decreased	18/36 (50%)	89
Lymph node pain	1/36 (2.8%)	1
Cardiac disorders
Cardiac disorder	1/36 (2.8%)	4
Palpitations	2/36 (5.6%)	4
Pericardial effusion	1/36 (2.8%)	1
Premature ventricular contractions	1/36 (2.8%)	1
Sinus bradycardia	1/36 (2.8%)	1
Sinus tachycardia	3/36 (8.3%)	15
Ear and labyrinth disorders
External ear pain	1/36 (2.8%)	1
Eye disorders
Eye disorder	1/36 (2.8%)	1
Eye pain	1/36 (2.8%)	4
Vision blurred	2/36 (5.6%)	5
Vitreous hemorrhage	1/36 (2.8%)	1
Gastrointestinal disorders
Abdominal distension	2/36 (5.6%)	2
Abdominal pain	5/36 (13.9%)	21
Constipation	13/36 (36.1%)	28
Diarrhea	11/36 (30.6%)	39
Dry mouth	2/36 (5.6%)	7
Dyspepsia	6/36 (16.7%)	8
Fecal incontinence	1/36 (2.8%)	1
Flatulence	3/36 (8.3%)	4
Gastritis	1/36 (2.8%)	1
Gastrointestinal disorder	7/36 (19.4%)	8
Gingival pain	2/36 (5.6%)	2
Hemorrhoids	1/36 (2.8%)	1
Mucositis oral	1/36 (2.8%)	1
Nausea	12/36 (33.3%)	55
Oral pain	5/36 (13.9%)	10
Rectal hemorrhage	1/36 (2.8%)	1
Salivary gland disorder	1/36 (2.8%)	2
Stomach pain	2/36 (5.6%)	4
Toothache	1/36 (2.8%)	1
Vomiting	6/36 (16.7%)	7
General disorders
Chest pain	5/36 (13.9%)	5
Chills	2/36 (5.6%)	2
Edema limbs	9/36 (25%)	37
Facial pain	1/36 (2.8%)	1
Fatigue	20/36 (55.6%)	107
Fever	6/36 (16.7%)	10
Gait abnormal	1/36 (2.8%)	1
Ill-defined disorder	2/36 (5.6%)	4
Irritability	5/36 (13.9%)	20
Localized edema	2/36 (5.6%)	3
Pain	14/36 (38.9%)	52
Infections and infestations
Bronchitis	1/36 (2.8%)	1
Gingival infection	1/36 (2.8%)	1
Opportunistic infection	1/36 (2.8%)	1
Otitis externa	1/36 (2.8%)	1
Peripheral nerve infection	1/36 (2.8%)	1
Phlebitis infective	1/36 (2.8%)	1
Sinusitis	2/36 (5.6%)	2
Skin infection	1/36 (2.8%)	1
Tooth infection	1/36 (2.8%)	1
Upper respiratory infection	5/36 (13.9%)	6
Urinary tract infection	1/36 (2.8%)	1
Vaginal infection	1/36 (2.8%)	1
Injury, poisoning and procedural complications
Bruising	1/36 (2.8%)	1
Dermatitis radiation	1/36 (2.8%)	1
Intraoperative gastrointestinal injury - Oral cavity NOS	1/36 (2.8%)	1
Investigations
Activated partial thromboplastin time prolonged	2/36 (5.6%)	2
Alanine aminotransferase increased	9/36 (25%)	17
Alkaline phosphatase increased	13/36 (36.1%)	70
Aspartate aminotransferase increased	21/36 (58.3%)	56
Bilirubin increased	4/36 (11.1%)	18
Coagulopathy	1/36 (2.8%)	1
Creatine phosphokinase increased	1/36 (2.8%)	1
Creatinine increased	5/36 (13.9%)	41
Haptoglobin decreased	1/36 (2.8%)	1
Laboratory test abnormal	1/36 (2.8%)	2
Leukocyte count decreased	11/36 (30.6%)	29
Lymphocyte count decreased	6/36 (16.7%)	16
Neutrophil count decreased	7/36 (19.4%)	18
Platelet count decreased	9/36 (25%)	19
Serum cholesterol increased	1/36 (2.8%)	1
Weight gain	4/36 (11.1%)	15
Weight loss	3/36 (8.3%)	13
Metabolism and nutrition disorders
Anorexia	8/36 (22.2%)	29
Blood bicarbonate decreased	3/36 (8.3%)	3
Blood glucose increased	22/36 (61.1%)	120
Blood uric acid increased	2/36 (5.6%)	3
Serum albumin decreased	6/36 (16.7%)	8
Serum calcium decreased	6/36 (16.7%)	8
Serum calcium increased	10/36 (27.8%)	24
Serum glucose decreased	7/36 (19.4%)	10
Serum magnesium decreased	1/36 (2.8%)	1
Serum magnesium increased	1/36 (2.8%)	1
Serum phosphate decreased	2/36 (5.6%)	2
Serum potassium decreased	8/36 (22.2%)	8
Serum potassium increased	2/36 (5.6%)	5
Serum sodium decreased	13/36 (36.1%)	26
Serum sodium increased	5/36 (13.9%)	7
Serum triglycerides increased	1/36 (2.8%)	1
Musculoskeletal and connective tissue disorders
Arthritis	9/36 (25%)	15
Back pain	9/36 (25%)	36
Bone pain	9/36 (25%)	51
Chest wall pain	2/36 (5.6%)	5
Fibrosis	1/36 (2.8%)	2
Joint disorder	1/36 (2.8%)	1
Joint pain	16/36 (44.4%)	111
Muscle weakness	7/36 (19.4%)	28
Muscle weakness upper limb	1/36 (2.8%)	1
Musculoskeletal disorder	5/36 (13.9%)	13
Myalgia	10/36 (27.8%)	34
Neck pain	3/36 (8.3%)	5
Pain in extremity	9/36 (25%)	43
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain	3/36 (8.3%)	4
Nervous system disorders
Cognitive disturbance	2/36 (5.6%)	6
Depressed level of consciousness	2/36 (5.6%)	2
Dizziness	4/36 (11.1%)	8
Extrapyramidal disorder	1/36 (2.8%)	1
Headache	10/36 (27.8%)	36
Memory impairment	5/36 (13.9%)	44
Peripheral motor neuropathy	4/36 (11.1%)	12
Peripheral sensory neuropathy	7/36 (19.4%)	26
Tremor	2/36 (5.6%)	3
Trigeminal nerve disorder	1/36 (2.8%)	2
Psychiatric disorders
Agitation	2/36 (5.6%)	3
Anxiety	11/36 (30.6%)	36
Confusion	3/36 (8.3%)	8
Depression	9/36 (25%)	27
Insomnia	11/36 (30.6%)	46
Libido decreased	1/36 (2.8%)	1
Renal and urinary disorders
Bladder spasm	1/36 (2.8%)	2
Protein urine positive	1/36 (2.8%)	1
Urethral pain	1/36 (2.8%)	1
Urinary frequency	1/36 (2.8%)	2
Urine discoloration	2/36 (5.6%)	3
Urogenital disorder	1/36 (2.8%)	1
Reproductive system and breast disorders
Breast pain	1/36 (2.8%)	2
Pelvic pain	1/36 (2.8%)	1
Vaginal discharge	2/36 (5.6%)	2
Vaginal dryness	1/36 (2.8%)	1
Vaginal hemorrhage	1/36 (2.8%)	1
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	4/36 (11.1%)	8
Bronchospasm	2/36 (5.6%)	5
Cough	6/36 (16.7%)	11
Dyspnea	9/36 (25%)	21
Pharyngolaryngeal pain	2/36 (5.6%)	3
Pulmonary hypertension	1/36 (2.8%)	1
Respiratory disorder	3/36 (8.3%)	4
Skin and subcutaneous tissue disorders
Alopecia	5/36 (13.9%)	24
Dry skin	2/36 (5.6%)	2
Nail disorder	2/36 (5.6%)	3
Pain of skin	2/36 (5.6%)	2
Pruritus	5/36 (13.9%)	11
Rash acneiform	2/36 (5.6%)	30
Rash desquamating	6/36 (16.7%)	19
Skin disorder	3/36 (8.3%)	4
Skin hyperpigmentation	2/36 (5.6%)	3
Sweating	5/36 (13.9%)	8
Urticaria	1/36 (2.8%)	1
Vascular disorders
Hematoma	1/36 (2.8%)	1
Hot flashes	24/36 (66.7%)	105
Hypertension	5/36 (13.9%)	16
Hypotension	1/36 (2.8%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.