Trial Using Docetaxel Cytoxan in Breast Cancers With High Recurrence Scores

• Sponsor: Emory University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00832338
• Collaborator: Sanofi (Industry)
• Enrollment: 23
• Locations: 3
• Arm: 1
• Duration (Months): 78
• Patients Per Site: 7.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to assess if docetaxel and cytoxan 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 before surgery, the investigators will be able to determine if your cancer is responsive to chemotherapy.

Condition or Disease	Intervention/Treatment	Phase
Breast Neoplasms; Breast Cancer; Cancer of the Breast	Drug: Docetaxel with Cytoxan; Drug: Dexamethasone	Phase 2

Detailed Description

Previous studies have shown that chemotherapy has the same effect on treating breast cancer whether you receive it before or after surgery. Receiving chemotherapy before surgery, rather than after surgery, may allow you to have less extensive surgery by shrinking the size of your cancer. The purpose of this study is to assess if docetaxel and cytoxan 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 before surgery, we will be able to determine if your cancer is responsive to chemotherapy. 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. You will only be eligible to enter this study if the recurrence score determined using the Oncotype DX assay is 25 or greater. Patients with hormone receptor-positive breast cancers with recurrence scores greater than or equal to 25 have been previously demonstrated to obtain a significant benefit from chemotherapy given after surgery.

In addition, researchers would like to examine proteins present in your blood and proteins present in your breast tissue. These additional parts of the study are voluntary and are NOT required to participate in this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 23 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Pre-Operative Docetaxel-Cytoxan (TC) in Patients With Hormone Receptor-Positive Cancers With Recurrence Scores ≥ 25
• Study Start Date: Apr 1, 2009
• Actual Primary Completion Date: Oct 1, 2015
• Actual Study Completion Date: Oct 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Docetaxel with Cytoxan Patients will be treated with docetaxel at 75 mg/m² concomitantly with cytoxan 600 mg/m² (TC) IV D1 every 3 weeks for 6 cycles. Due to known toxicity of docetaxel, all patients require dexamethasone 4 mg twice daily (BID) PO for 3 consecutive days starting 12-24 hours prior to each dose of docetaxel to minimize hypersensitivity reactions and fluid retention.	Drug: Docetaxel with Cytoxan; Docetaxel 75 mg/m² plus cytoxan 600 mg/m² every 3 weeks for 6 cycles.; Other Names: Docetaxel Cytoxan ; Drug: Dexamethasone; Dexamethasone 4 mg BID PO for 3 consecutive days starting 12-24 hours prior to each dose of docetaxel.; Other Names: Decadron

Outcome Measures

Primary Outcome Measures

1. Pathologic Response to Pre-operative Docetaxel and Cytoxan (TC) [At time of definitive surgery]

   Patients were assessed for surgery after 6 cycles of TC (18 weeks). Pathologic stage was determined based on size of tumor and degree of lymph node involvement at the time of surgery, whereas clinical stage pre-operatively was determined by clinical assessment and imaging. 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.

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).

• No evidence of disease outside the breast or chest wall, except ipsilateral axillary or internal mammary lymph nodes.

• 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 fluorescence in situ hybridization [FISH] non-amplified)

• Recurrence score ≥ 25 using Oncotype DX 21-gene assay

• Patients must have measurable disease as defined by palpable lesion with both diameters ≥ 1cm measurable with caliper or a positive mammogram or ultrasound with at least one dimension ≥ 1cm. 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 the 14 days if palpable. If not palpable, a mammogram or MRI must be done within 14 days. If palpable, a mammogram or MRI must be done within 2 months prior to study entry. If clinically indicated, xrays and scans must be done within 28 days of study entry.

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

• No prior chemotherapy, hormonal therapy, biologic therapy or radiation therapy for breast cancer.

• 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 Cockroft Gault equation.

• Patients must be at least 18 years of age.

Exclusion Criteria:

• 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.

• No medical, psychological or surgical condition which the investigator feels might compromise study participation.

• No 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.

• No 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.

• No serious, uncontrolled, concurrent infection(s).

• No 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.

• No major surgery within 28 days of study entry.

• No 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
• Sanofi

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, Principal Investigator, Emory University
• ClinicalTrials.gov Identifier: NCT00832338
• Other Study ID Numbers: IRB00012185; WCI1505-08
• First Posted: Jan 30, 2009
• Last Update Posted: Aug 31, 2017
• Last Verified: Aug 1, 2017

• Keywords provided by Elisavet Paplomata, Principal Investigator, Emory University: Breast cancer; Tumors, Breast; Cancer of the breast
• Additional relevant MeSH terms: Breast Neoplasms; Recurrence; Dexamethasone; Docetaxel; Cyclophosphamide

Study Results

Participant Flow

Recruitment Details	Patients were recruited from April 2009 to October 2015 at Winship Cancer Institute of Emory University, Emory University Hospital Midtown, and Grady Memorial Hospital.

Arm/Group Title	Docetaxel With Cytoxan
Arm/Group Description	Patients will be treated with docetaxel at 75 mg/m² concomitantly with cytoxan 600 mg/m² (TC) IV D1 every 3 weeks for 6 cycles. Due to known toxicity of docetaxel, all patients require dexamethasone 4 mg twice daily (BID) PO for 3 consecutive days starting 12-24 hours prior to each dose of docetaxel to minimize hypersensitivity reactions and fluid retention. Docetaxel with Cytoxan: Docetaxel 75 mg/m² plus cytoxan 600 mg/m² every 3 weeks for 6 cycles. Dexamethasone: Dexamethasone 4 mg BID PO for 3 consecutive days starting 12-24 hours prior to each dose of docetaxel.
Period Title: Overall Study
STARTED	23
COMPLETED	23
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Docetaxel With Cytoxan
Arm/Group Description	Patients will be treated with docetaxel at 75 mg/m² concomitantly with cytoxan 600 mg/m² (TC) IV D1 every 3 weeks for 6 cycles. Due to known toxicity of docetaxel, all patients require dexamethasone 4 mg BID PO for 3 consecutive days starting 12-24 hours prior to each dose of docetaxel to minimize hypersensitivity reactions and fluid retention. Docetaxel with Cytoxan: Docetaxel 75 mg/m² plus cytoxan 600 mg/m² every 3 weeks for 6 cycles. Dexamethasone: Dexamethasone 4 mg BID PO for 3 consecutive days starting 12-24 hours prior to each dose of docetaxel.
Overall Participants	23
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.91 (9.69)
Sex: Female, Male (Count of Participants)
Female	21 91.3%
Male	2 8.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 4.3%
Not Hispanic or Latino	20 87%
Unknown or Not Reported	2 8.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	11 47.8%
White	10 43.5%
More than one race	0 0%
Unknown or Not Reported	2 8.7%
Region of Enrollment (Count of Participants)
United States	23 100%

Outcome Measures

1. Primary Outcome

Title	Pathologic Response to Pre-operative Docetaxel and Cytoxan (TC)
Description	Patients were assessed for surgery after 6 cycles of TC (18 weeks). Pathologic stage was determined based on size of tumor and degree of lymph node involvement at the time of surgery, whereas clinical stage pre-operatively was determined by clinical assessment and imaging. 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

Staging information was not collected for two patients.

Arm/Group Title	Docetaxel With Cytoxan
Arm/Group Description	Patients will be treated with docetaxel at 75 mg/m² concomitantly with cytoxan 600 mg/m² (TC) IV D1 every 3 weeks for 6 cycles. Due to known toxicity of docetaxel, all patients require dexamethasone 4 mg BID PO for 3 consecutive days starting 12-24 hours prior to each dose of docetaxel to minimize hypersensitivity reactions and fluid retention. Docetaxel with Cytoxan: Docetaxel 75 mg/m² plus cytoxan 600 mg/m² every 3 weeks for 6 cycles. Dexamethasone: Dexamethasone 4 mg BID PO for 3 consecutive days starting 12-24 hours prior to each dose of docetaxel.
Measure Participants	21
Downstaged	12 52.2%
Stable	4 17.4%
Upstaged	5 21.7%

Adverse Events

Arm/Group Title	Docetaxel With Cytoxan
Arm/Group Description	Patients will be treated with docetaxel at 75 mg/m² concomitantly with cytoxan 600 mg/m² (TC) IV D1 every 3 weeks for 6 cycles. Due to known toxicity of docetaxel, all patients require dexamethasone 4 mg BID PO for 3 consecutive days starting 12-24 hours prior to each dose of docetaxel to minimize hypersensitivity reactions and fluid retention. Docetaxel with Cytoxan: Docetaxel 75 mg/m² plus cytoxan 600 mg/m² every 3 weeks for 6 cycles. Dexamethasone: Dexamethasone 4 mg BID PO for 3 consecutive days starting 12-24 hours prior to each dose of docetaxel.
All Cause Mortality
	Docetaxel With Cytoxan
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Docetaxel With Cytoxan
	Affected / at Risk (%)	# Events
Total	1/23 (4.3%)
Infections and infestations
Febrile neutropenia	1/23 (4.3%)
Other (Not Including Serious) Adverse Events
	Docetaxel With Cytoxan
	Affected / at Risk (%)	# Events
Total	21/23 (91.3%)
Blood and lymphatic system disorders
Thrombocytopenia	1/23 (4.3%)
Anemia	1/23 (4.3%)
Lower extremity edema	8/23 (34.8%)
Cardiac disorders
Tachycardia	1/23 (4.3%)
Eye disorders
Watery eyes	3/23 (13%)
Gastrointestinal disorders
Dyspepsia	1/23 (4.3%)
Colitis	1/23 (4.3%)
Anorexia	3/23 (13%)
Nausea	4/23 (17.4%)
Vomiting	2/23 (8.7%)
Diarrhea	6/23 (26.1%)
Constipation	4/23 (17.4%)
Oral mucositis	4/23 (17.4%)
Dysgeusia	6/23 (26.1%)
General disorders
Fever	1/23 (4.3%)
Chills	2/23 (8.7%)
Weight gain	2/23 (8.7%)
Fatigue	16/23 (69.6%)
Abdominal pain	1/23 (4.3%)
Insomnia	5/23 (21.7%)
Immune system disorders
Allergic reaction	1/23 (4.3%)
Infections and infestations
Upper respiratory infection	1/23 (4.3%)
Metabolism and nutrition disorders
Hyponatremia	1/23 (4.3%)
Increased creatinine	1/23 (4.3%)
Hyperglycemia	2/23 (8.7%)
Musculoskeletal and connective tissue disorders
Bone pain	1/23 (4.3%)
Myalgias	2/23 (8.7%)
Arthralgia	6/23 (26.1%)
Nervous system disorders
Syncope	1/23 (4.3%)
Memory impairment	1/23 (4.3%)
Sensory peripheral neuropathy	12/23 (52.2%)
Headache	5/23 (21.7%)
Psychiatric disorders
Anxiety	5/23 (21.7%)
Depression	3/23 (13%)
Mood swings	1/23 (4.3%)
Reproductive system and breast disorders
Irregular menstruation	1/23 (4.3%)
Respiratory, thoracic and mediastinal disorders
Laryngeal inflammation	1/23 (4.3%)
Dyspnea	8/23 (34.8%)
Cough	6/23 (26.1%)
Skin and subcutaneous tissue disorders
Pruritis	1/23 (4.3%)
Nail loss	2/23 (8.7%)
Nail discoloration	6/23 (26.1%)
Maculopapular rash	5/23 (21.7%)
Alopecia	8/23 (34.8%)

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.