Exemestane or Docetaxel-Cytoxan in Low Recurrence Score Cancers

• Sponsor: Emory University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00941330
• Collaborator: Pfizer (Industry)
• Enrollment: 31
• Locations: 3
• Arms: 2
• Duration (Months): 70
• Patients Per Site: 10.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The patients are being asked to take part in this study because they have a hormone receptor-positive breast cancer (contains estrogen and/or progesterone receptors) and their doctor has told them that they have an option to receive chemotherapy or hormonal therapy before surgery. The purpose of this study is to assess if chemotherapy using docetaxel and cytoxan (TC) or hormonal therapy using exemestane can shrink the size of their breast tumor and allow them to preserve the breast or have less extensive surgery on their breast.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Exemestane; Drug: Docetaxel; Drug: Cytoxan	Phase 2

Detailed Description

The purpose of this study is to assess if chemotherapy using docetaxel and cytoxan (TC) or hormonal therapy using exemestane can shrink the size of your breast tumor and allow you to preserve your breast or have less extensive surgery on your breast. Additionally, by receiving chemotherapy or hormonal therapy before surgery, we will be able to determine if the treatment you receive is effective in treating your cancer. Prior to entering this study, a special test, called the Oncotype DX assay, will be performed on a small amount of your cancer from the biopsy you had at the time you were diagnosed with breast cancer, to determine the likelihood that your cancer will benefit from and shrink with chemotherapy and hormonal therapy. You will only be eligible to enter this study if the recurrence score of your cancer determined using the Oncotype DX assay is less than or equal to 24. Patients with hormone receptor-positive breast cancers with recurrence scores less than or equal to 24 have been previously demonstrated to obtain a larger benefit from hormonal therapy, compared to chemotherapy, when these agents are given after surgery. The ability of hormonal agents and chemotherapy to shrink cancers prior to surgery has not been specifically examined in hormone receptor-positive cancers with recurrence scores less than or equal to 24.

Study Design

• Study Type: Interventional
• Actual Enrollment: 31 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized Phase II Trial of Pre-Operative Docetaxel-Cytoxan (TC) or Exemestane in Patients With Hormone Receptor-Positive Breast Cancers With Recurrence Scores Greater Than 10 (≥ 11) and Less Than 25 (≤ 24)
• Study Start Date: Jul 1, 2009
• Actual Primary Completion Date: May 1, 2015
• Actual Study Completion Date: May 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A: Exemestane ARM A: Patients will be treated with exemestane.	Drug: Exemestane; 25 mg daily by mouth for 6 to 12 months.; Other Names: Aromasin
Active Comparator: B: Docetaxel and Cytoxan ARM B: Patients will be treated with docetaxel and cytoxan.	Drug: Docetaxel; Docetaxel (75 mg/m²) into a vein once every 3 weeks for 6 cycles (6 times in about 24 weeks).; Other Names: Taxotere ; Drug: Cytoxan; Cytoxan (600 mg/m²) into a vein once every 3 weeks for 6 cycles (6 times in about 24 weeks).; Other Names: Cyclophosphamide

Outcome Measures

Primary Outcome Measures

1. Pathologic Complete Response [At time of definitive surgery]

   Patients must have measurable disease by clinical examination. Pathologic complete response (pCR): Absence of invasive breast cancer in the breast (mastectomy or lumpectomy) specimen at the time of definitive surgery. Presence of in situ cancer alone will be considered a pCR but may be recorded separately. If pathologic stage was the same as clinical stage, it was called stable; if it was higher, upstaged (worse outcome); if lower, downstaged (better outcome). Pathologic stage was determined by Emory board-certified pathologists.

Secondary Outcome Measures

1. Response Rate by Imaging [Every 2 months up to 3 years]

   Arm A and recurrence score ≤10: Patients will have radiologic assessment of response to exemestane by clinical examination every 4 weeks and by radiologic assessment every 2 months. Once maximal response has been achieved (stable disease for 2 months after at least 4 months of treatment by radiologic assessment) or when 12 months of therapy has been given patients will proceed to surgery. Arm B: Patients will be assessed for surgery after 6 cycles of docetaxel and cytoxan (TC) (18 weeks). On arm A and recurrence score ≤10 patients will be reassessed for surgery once maximal radiologic response is achieved. On arm B, patients will be reassessed for surgery after 6 cycles of TC (18 weeks). Radiographic images were analyzed by a breast radiologist who looked at preoperative and postoperative breast mass imaging. If mass was smaller/less extensive, it was considered improved.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Signed informed consent.

• Histologically or cytologically confirmed breast carcinoma.

• Early stage breast cancer (T1c-3, clinically node-negative-3 [cN0-3], CM0).

• Pre-treatment biopsy with the following characteristics:

• Hormone receptor-positive cancer as defined as ER and/or progesterone receptor (PR)-positive by standard immunohistochemistry (IHC)

• HER2-negative (HER2 ≤ 2 by IHC; if HER2 2+ by IHC must be fluorescent in situ hybridization [FISH] non-amplified)

• Recurrence score < 25 using Oncotype DX 21-gene recurrence score assay

• Patients must have measurable disease as defined by palpable lesion with both diameters ≥ 1 cm measurable with caliper or a positive mammogram or ultrasound with at least one dimension ≥ 1 cm. Screening mammogram of the contralateral breast must be performed within past 12 months per standard practice guidelines. Clip placement is required for study entry.

• Baseline measurements of the indicator lesions must be recorded on the Patient Registration Form. To be valid for baseline, the measurements must have been made within 14 days of study enrollment if palpable. If not palpable, a mammogram or MRI must be done within 14 days. If palpable, a diagnostic mammogram of the affected breast or MRI must be done within 2 months prior to study enrollment, defined as date of signed, informed consent. If clinically indicated, staging xrays and scans must be done within 28 days of study entry.

• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.

• Adequate organ function within 14 days of study entry:

• Bone marrow function: absolute neutrophil count (ANC) ≥ 1500/mm³, Hgb > 8.0 g/dl and platelet count ≥ 100,000/mm³.

• Hepatic function: total bilirubin < upper limit of normal (ULN). Serum glutamic oxaloacetic transaminase (SGOT) (AST) or serum glutamic pyruvic transaminase (SGPT) (ALT) and alkaline phosphatase ≤ 1.5 x ULN).

• Renal function: calculated creatinine clearance (CrCl) ≥ 30 mL/min using the Cockcroft Gault equation.

• Patients must be at least 18 years of age.

Exclusion Criteria:

• Evidence of disease outside the breast or chest wall, except ipsilateral axillary or internal mammary lymph nodes.

• Prior chemotherapy, hormonal therapy, biologic therapy or radiation therapy for breast cancer.

• Pregnant or lactating women are not eligible. Women of childbearing potential must have a negative serum pregnancy test completed within 7 days of study entry, and use an appropriate form of birth control throughout the trial period.

• Medical, psychological or surgical condition which the investigator feels might compromise study participation.

• Patients with history within the last 5 years of previous or current malignancy at other sites with the exception of adequately treated carcinoma in-situ of the cervix or basal or squamous cell carcinoma of the skin. Patients with a history of other malignancies who remain disease free for greater than five years are eligible.

• Evidence of peripheral or sensory neuropathy.

• Patients with a history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80 are excluded from participation.

• Serious, uncontrolled, concurrent infection(s).

• Clinically significant cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 12 months prior to study entry.

• Major surgery within 28 days of study entry.

• Evidence of central nervous system (CNS) metastases.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Grady Memorial Hospital	Atlanta	Georgia	United States	30303
2	Emory University Hospital Midtown	Atlanta	Georgia	United States	30308
3	Emory University Winship Cancer Institute	Atlanta	Georgia	United States	30322

Sponsors and Collaborators

• Emory University
• Pfizer

Investigators

• Principal Investigator: Elisavet Paplomata, MD, Emory University Winship Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Elisavet Paplomata, MD, Emory University
• ClinicalTrials.gov Identifier: NCT00941330
• Other Study ID Numbers: IRB00012969; WCI1534-08
• First Posted: Jul 17, 2009
• Last Update Posted: Apr 10, 2017
• Last Verified: Feb 1, 2017

• Keywords provided by Elisavet Paplomata, MD, Emory University: Breast, Male; Breast, Female
• Additional relevant MeSH terms: Breast Neoplasms; Recurrence; Cyclophosphamide; Docetaxel; Exemestane

Study Results

Participant Flow

Recruitment Details	From June 2009 to December 2014, patients were recruited at Winship Cancer Institute of Emory University, Emory University Hospital Midtown, and Grady Health System, all in Atlanta, Georgia.
Pre-assignment Detail	Five patients were not assigned to a treatment arm. One patient was ineligible for the study due to a low Oncotype score. Three patients did not like randomized treatment. One patient had disease progression.

Arm/Group Title	A: Exemestane	B: Docetaxel and Cytoxan
Arm/Group Description	ARM A: Patients will be treated with exemestane. Exemestane: 25 mg daily by mouth for 6 to 12 months.	ARM B: Patients will be treated with docetaxel and cytoxan. Docetaxel: Docetaxel (75 mg/m²) into a vein once every 3 weeks for 6 cycles (6 times in about 24 weeks). Cytoxan: Cytoxan (600 mg/m²) into a vein once every 3 weeks for 6 cycles (6 times in about 24 weeks).
Period Title: Overall Study
STARTED	15	11
COMPLETED	14	9
NOT COMPLETED	1	2

Baseline Characteristics

Arm/Group Title	A: Exemestane	B: Docetaxel and Cytoxan	Total
Arm/Group Description	ARM A: Patients will be treated with exemestane. Exemestane: 25 mg daily by mouth for 6 to 12 months.	ARM B: Patients will be treated with docetaxel and cytoxan. Docetaxel: Docetaxel (75 mg/m²) into a vein once every 3 weeks for 6 cycles (6 times in about 24 weeks). Cytoxan: Cytoxan (600 mg/m²) into a vein once every 3 weeks for 6 cycles (6 times in about 24 weeks).	Total of all reporting groups
Overall Participants	15	11	26
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	12 80%	9 81.8%	21 80.8%
>=65 years	3 20%	2 18.2%	5 19.2%
Sex: Female, Male (Count of Participants)
Female	15 100%	11 100%	26 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	15 100%	11 100%	26 100%

Outcome Measures

1. Primary Outcome

Title	Pathologic Complete Response
Description	Patients must have measurable disease by clinical examination. Pathologic complete response (pCR): Absence of invasive breast cancer in the breast (mastectomy or lumpectomy) specimen at the time of definitive surgery. Presence of in situ cancer alone will be considered a pCR but may be recorded separately. If pathologic stage was the same as clinical stage, it was called stable; if it was higher, upstaged (worse outcome); if lower, downstaged (better outcome). Pathologic stage was determined by Emory board-certified pathologists.
Time Frame	At time of definitive surgery

Outcome Measure Data

Analysis Population Description

One patient in Arm B did not have surgery.

Arm/Group Title	A: Exemestane	B: Docetaxel and Cytoxan
Arm/Group Description	ARM A: Patients will be treated with exemestane. Exemestane: 25 mg daily by mouth for 6 to 12 months.	ARM B: Patients will be treated with docetaxel and cytoxan. Docetaxel: Docetaxel (75 mg/m²) into a vein once every 3 weeks for 6 cycles (6 times in about 24 weeks). Cytoxan: Cytoxan (600 mg/m²) into a vein once every 3 weeks for 6 cycles (6 times in about 24 weeks).
Measure Participants	14	8
Downstaged	5 33.3%	1 9.1%
Stable	4 26.7%	2 18.2%
Upstaged	5 33.3%	5 45.5%

2. Secondary Outcome

Title	Response Rate by Imaging
Description	Arm A and recurrence score ≤10: Patients will have radiologic assessment of response to exemestane by clinical examination every 4 weeks and by radiologic assessment every 2 months. Once maximal response has been achieved (stable disease for 2 months after at least 4 months of treatment by radiologic assessment) or when 12 months of therapy has been given patients will proceed to surgery. Arm B: Patients will be assessed for surgery after 6 cycles of docetaxel and cytoxan (TC) (18 weeks). On arm A and recurrence score ≤10 patients will be reassessed for surgery once maximal radiologic response is achieved. On arm B, patients will be reassessed for surgery after 6 cycles of TC (18 weeks). Radiographic images were analyzed by a breast radiologist who looked at preoperative and postoperative breast mass imaging. If mass was smaller/less extensive, it was considered improved.
Time Frame	Every 2 months up to 3 years

Outcome Measure Data

Analysis Population Description

Data were not available for 5 patients (4 withdrew and 1 did not have surgery).

Arm/Group Title	A: Exemestane	B: Docetaxel and Cytoxan
Arm/Group Description	ARM A: Patients will be treated with exemestane. Exemestane: 25 mg daily by mouth for 6 to 12 months.	ARM B: Patients will be treated with docetaxel and cytoxan. Docetaxel: Docetaxel (75 mg/m²) into a vein once every 3 weeks for 6 cycles (6 times in about 24 weeks). Cytoxan: Cytoxan (600 mg/m²) into a vein once every 3 weeks for 6 cycles (6 times in about 24 weeks).
Measure Participants	15	6
Improved	9 60%	2 18.2%
Stable	6 40%	4 36.4%

Adverse Events

Arm/Group Title	A: Exemestane		B: Docetaxel and Cytoxan
Arm/Group Description	ARM A: Patients will be treated with exemestane. Exemestane: 25 mg daily by mouth for 6 to 12 months.		ARM B: Patients will be treated with docetaxel and cytoxan. Docetaxel: Docetaxel (75 mg/m²) into a vein once every 3 weeks for 6 cycles (6 times in about 24 weeks). Cytoxan: Cytoxan (600 mg/m²) into a vein once every 3 weeks for 6 cycles (6 times in about 24 weeks).
All Cause Mortality
	A: Exemestane		B: Docetaxel and Cytoxan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	A: Exemestane		B: Docetaxel and Cytoxan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		1/11 (9.1%)
Gastrointestinal disorders
Gastroenteritis and Severe Diarrhea	0/15 (0%)		1/11 (9.1%)
Other (Not Including Serious) Adverse Events
	A: Exemestane		B: Docetaxel and Cytoxan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/15 (86.7%)		10/11 (90.9%)
Blood and lymphatic system disorders
Hypokalemia	1/15 (6.7%)		0/11 (0%)
Bruising	2/15 (13.3%)		0/11 (0%)
Anemia	0/15 (0%)		2/11 (18.2%)
Eye disorders
Floaters	1/15 (6.7%)		0/11 (0%)
Conjunctivitis	0/15 (0%)		1/11 (9.1%)
Watery Eyes	0/15 (0%)		1/11 (9.1%)
Gastrointestinal disorders
Diarrhea	1/15 (6.7%)		1/11 (9.1%)
Constipation	0/15 (0%)		2/11 (18.2%)
Vomiting	1/15 (6.7%)		0/11 (0%)
General disorders
Fever	1/15 (6.7%)		1/11 (9.1%)
Lower Extremity Edema	1/15 (6.7%)		2/11 (18.2%)
Fatigue	7/15 (46.7%)		9/11 (81.8%)
Bloating	1/15 (6.7%)		0/11 (0%)
Hot Flashes	8/15 (53.3%)		2/11 (18.2%)
Headache	3/15 (20%)		1/11 (9.1%)
Nausea	1/15 (6.7%)		2/11 (18.2%)
Dizziness	1/15 (6.7%)		1/11 (9.1%)
Insomnia	7/15 (46.7%)		3/11 (27.3%)
Chest Pain	0/15 (0%)		1/11 (9.1%)
Dysgeusia	0/15 (0%)		1/11 (9.1%)
Chills	1/15 (6.7%)		0/11 (0%)
Irritability	3/15 (20%)		1/11 (9.1%)
Hepatobiliary disorders
Elevated Liver Enzymes	0/15 (0%)		1/11 (9.1%)
Immune system disorders
Allergic Reaction	0/15 (0%)		2/11 (18.2%)
Metabolism and nutrition disorders
Anorexia	1/15 (6.7%)		0/11 (0%)
Weight Gain	1/15 (6.7%)		1/11 (9.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	7/15 (46.7%)		2/11 (18.2%)
Arthritis	1/15 (6.7%)		0/11 (0%)
Myalgia	3/15 (20%)		1/11 (9.1%)
Gait Disturbance	1/15 (6.7%)		0/11 (0%)
Bone Pain	2/15 (13.3%)		1/11 (9.1%)
Nervous system disorders
Peripheral Sensory Neuropathy	2/15 (13.3%)		2/11 (18.2%)
Memory Impairment	2/15 (13.3%)		0/11 (0%)
Syncope	0/15 (0%)		1/11 (9.1%)
Psychiatric disorders
Anxiety	3/15 (20%)		0/11 (0%)
Depression	4/15 (26.7%)		1/11 (9.1%)
Renal and urinary disorders
Urinary Incontinence	1/15 (6.7%)		0/11 (0%)
Hematuria	0/15 (0%)		1/11 (9.1%)
Reproductive system and breast disorders
Vaginal Hemorrhage	1/15 (6.7%)		0/11 (0%)
Respiratory, thoracic and mediastinal disorders
Rhinitis	2/15 (13.3%)		1/11 (9.1%)
Cough	1/15 (6.7%)		2/11 (18.2%)
Dyspnea	1/15 (6.7%)		2/11 (18.2%)
Epistaxis	0/15 (0%)		1/11 (9.1%)
Laryngeal Inflammation	1/15 (6.7%)		1/11 (9.1%)
Skin and subcutaneous tissue disorders
Dry Mouth	1/15 (6.7%)		0/11 (0%)
Oral Mucositis	2/15 (13.3%)		1/11 (9.1%)
Alopecia	1/15 (6.7%)		2/11 (18.2%)

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.