Docetaxel Followed by Surgery in Treating Women With Stage II or Stage III Breast Cancer

• Sponsor: Vanderbilt-Ingram Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00343512
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 34
• Locations: 2
• Arm: 1
• Duration (Months): 84.9
• Patients Per Site: 17
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

RATIONALE: Dose-dense scheduling with (peg)filgrastim support may improve the clinical and pathologic complete response rate (pCR) and safety profile of single agent neoadjuvant docetaxel therapy.

PURPOSE: To evaluate whether dose-dense scheduling with (peg)filgrastim support may improve the clinical and pathologic complete response rate (pCR) and safety profile of single agent neoadjuvant docetaxel therapy. To determine the changes in molecular markers that occurs with single agent docetaxel, tissue will be obtained at the end of the four cycles of docetaxel (either by repeat biopsy or definitive surgery).

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: docetaxel; Genetic: protein expression analysis; Other: laboratory biomarker analysis; Procedure: biopsy; Procedure: conventional surgery; Procedure: neoadjuvant therapy	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Pathologic complete response rate (pCR) of dose dense docetaxel in the neoadjuvant setting.

Secondary

• Safety and toxic effects of this regimen in these patients.

• Tumor response rate (as measured by ultrasound) in patients treated with this regimen.

• Determine whether early changes in markers of cell cycle position, proliferation, or apoptosis correlate with pathologic complete response rate in these patients.

• Determine whether the molecular profile that predicts for chemoresponsiveness also predicts for response to radiotherapy (as measured by local recurrence) in these patients.

• Determine whether tumors that demonstrate the greatest degree of change in protein expression patterns from pre- to post-docetaxel treatment will also be those that are most sensitive to chemotherapy (as measured by pathologic response rate) in these patients.

OUTLINE: This is a nonrandomized, open-label, pilot study.

• Tissue Collection: Patients undergo tumor core biopsy (6-8 cores) and blood collection prior to initiating neoadjuvant docetaxel.

• Neoadjuvant docetaxel with hematopoietic support: Patients receive docetaxel IV over 1 hour on day 1. Patients also receive pegfilgrastim subcutaneously (SC) on day 1 or 2 of each course OR filgrastim (G-CSF) or sargramostim (GM-CSF) SC daily beginning between day 2-4 of each course and continuing until blood counts recover. Treatment repeats every 14 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

• Surgery: Within 4-6 weeks after completion of neoadjuvant docetaxel, patients undergo definitive surgery.

Patients undergo tumor biopsy and blood collection periodically for pharmacokinetic, genetic, and molecular biomarker correlative studies. Samples are examined for changes in p21 protein expression (and/or p21 phosphorylation) and the protein expression profile.

After completion of study treatment, patients are followed at least every 6 months for 3 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 34 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pilot Study of Neoadjuvant Dose Dense Docetaxel With Correlative Molecular Studies in Stage II/III Breast Cancer
• Study Start Date: Feb 1, 2004
• Actual Primary Completion Date: Mar 1, 2008
• Actual Study Completion Date: Mar 1, 2011

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Therapeutic Intervention

Drug: docetaxel; Docetaxel 75 mg/m2 IV (1-hour infusion) on day 1 of each cycle (cycle = 2 weeks) x 4 cycles; Other Names: Taxotere ; Genetic: protein expression analysis; protein expression analysis; Other: laboratory biomarker analysis; laboratory biomarker analysis; Procedure: biopsy; biopsy; Procedure: conventional surgery; conventional surgery; Procedure: neoadjuvant therapy; neoadjuvant therapy

Outcome Measures

Primary Outcome Measures

1. Number Participants to Achieve Pathologic Complete Response [3 month]

   whether or not patient has pathologic complete response (pCR) to dose dense docetaxel in the neoadjuvant setting (pCR = no residual viable tumor on histologic analysis)

Secondary Outcome Measures

1. Safety Profile Based on Number of Patients With Each Worst-grade Toxicity [Through 30 days after completion of treatment]

   Not all participants necessarily have an adverse event, thus not everyone will be accounted for in worst-grade toxicities. Likewise, one participant can potentially have more than one event in various grades 1-5 which accounts for the difference in number of patients analyzed and total number in the worst-grade toxicity tables. Tables represent the number of patients with worst-grade toxicity at each of five grades (grade 1, least severe; to grade 5, most severe) following NCI Common Toxicity Criteria

2. Tumor Response as Measured by Ultrasound [At screening, 8 weeks and at surgery (within 14-21 days)]

   Progressive disease (PD): >=20% increase in sum of longest diameter (LD) of target lesion(s), taking as reference smallest sum LD recorded since treatment started. Complete response (CR): disappearance of all target lesions. Partial response (PR): >=30% decrease in sum of LD of target lesion(s), taking as reference baseline sum LD. Stable disease (SD): neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD.

Eligibility Criteria

Criteria

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

DISEASE CHARACTERISTICS:

Inclusion:

• Histologically or cytologically confirmed invasive carcinoma of the breast by core biopsy

• Tumor ≥ 2 cm in greatest dimension(may be either node positive or node negative disease

• Patients with non-metastatic breast cancer who are in the judgment of the treating medical oncologist considered to be of sufficiently high risk to warrant adjuvant chemotherapy

• Patients with internal mammary, supraclavicular and/or axillary node involvement are eligible. Patients with inflammatory breast cancer are eligible

• Patients with T0 disease but palpable and measurable adenopathy are eligible for this trial. All sites of disease should be noted and followed

• Hormone receptor status:

• Not specified

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1

• Menopausal status not specified

• Female ≥ 18 years old

• Absolute neutrophil count ≥ 1,000/mm^3

• Hemoglobin ≥ 8 g/dL

• Platelet count ≥ 100,000/mm^3

• Creatinine ≤ 1.5 times upper limit of normal (ULN)

• Bilirubin normal

• Alkaline phosphatase (AP), AST, and ALT meeting 1 of the following criteria:

• AP normal AND AST or ALT ≤ 5 times ULN

• AP ≤ 2.5 times ULN AND AST or ALT ≤ 1.5 times ULN

• AP ≤ 5 times ULN AND AST or ALT normal

• Women of child-bearing potential, must have a negative serum pregnancy test and must use effective contraception for the duration of the study and for at least 6 months after completion of study treatment

• Patients with prior malignancies are eligible if they have been disease free for ≥ 5 years. Patients with curative treatment of non-melanomatous skin cancer, carcinoma in situ of the cervix, contralateral DCIS treated with mastectomy are eligible even if it is diagnosed in < 5 years.

PRIOR CONCURRENT THERAPY:

• No prior anthracycline or taxane-based chemotherapy. Patients who received chemoprevention are eligible if the chemopreventive agent has been discontinued for at least one year prior to enrollment in the current study.

• At least 1 year since prior tamoxifen for breast cancer prevention

Exclusion:

• Prior radiotherapy to the ipsilateral breast

• Patients who have had radiation to the contralateral breast are eligible

• Evidence of distant metastatic disease (i.e., lung, liver, bone, brain)

• Pregnant of breastfeeding

• Patients who have congestive heart failure, angina pectoris, uncontrolled cardiac arrhythmia, or other significant heart disease, or who have had a myocardial infarction within the past year

• Patients with > grade 1 peripheral neuropathy

• Patients with a history of hypersensitivity reaction to products containing polysorbate 80 (Tween 80)

• Patients receiving an investigational anticancer drug within 3 weeks of registration

• Patients with serious medical illness that in the judgment of the treating physician, places the patient at risk.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Meharry Medical College	Nashville	Tennessee	United States	37208
2	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee	United States	37232-6838

Sponsors and Collaborators

• Vanderbilt-Ingram Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: A. Bapsi Chakravarthy, MD, Vanderbilt-Ingram Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bapsi Chak, MD, Associate Professor; Radiation Oncologist, Vanderbilt-Ingram Cancer Center
• ClinicalTrials.gov Identifier: NCT00343512
• Other Study ID Numbers: VICC BRE 0368; VICC-BRE-0368; VICC-11239
• First Posted: Jun 23, 2006
• Last Update Posted: Apr 27, 2012
• Last Verified: Apr 1, 2012

• Keywords provided by Bapsi Chak, MD, Associate Professor; Radiation Oncologist, Vanderbilt-Ingram Cancer Center: inflammatory breast cancer; stage II breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer
• Additional relevant MeSH terms: Breast Neoplasms; Docetaxel

Study Results

Participant Flow

Recruitment Details	This study enrolled patients from February 2004 to September 2007.
Pre-assignment Detail	A total of 39 people were consented, one of which was ineligible. Four patients withdrew from the study before beginning treatment.

Arm/Group Title	Therapeutic Intervention
Arm/Group Description	Docetaxel 75 mg/m2 IV (1-hour infusion) on day 1 of each cycle (cycle = 2 weeks) x 4 cycles
Period Title: Overall Study
STARTED	34
COMPLETED	32
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Therapeutic Intervention
Arm/Group Description	Docetaxel 75 mg/m2 IV (1-hour infusion) on day 1 of each cycle (cycle = 2 weeks) x 4 cycles
Overall Participants	34
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	34 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47 (1)
Sex: Female, Male (Count of Participants)
Female	34 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	34 100%

Outcome Measures

1. Primary Outcome

Title	Number Participants to Achieve Pathologic Complete Response
Description	whether or not patient has pathologic complete response (pCR) to dose dense docetaxel in the neoadjuvant setting (pCR = no residual viable tumor on histologic analysis)
Time Frame	3 month

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Therapeutic Intervention
Arm/Group Description	Docetaxel 75 mg/m2 IV (1-hour infusion) on day 1 of each cycle (cycle = 2 weeks) x 4 cycles
Measure Participants	34
pCR: Yes	5 14.7%
pCR: No	29 85.3%

2. Secondary Outcome

Title	Safety Profile Based on Number of Patients With Each Worst-grade Toxicity
Description	Not all participants necessarily have an adverse event, thus not everyone will be accounted for in worst-grade toxicities. Likewise, one participant can potentially have more than one event in various grades 1-5 which accounts for the difference in number of patients analyzed and total number in the worst-grade toxicity tables. Tables represent the number of patients with worst-grade toxicity at each of five grades (grade 1, least severe; to grade 5, most severe) following NCI Common Toxicity Criteria
Time Frame	Through 30 days after completion of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Therapeutic Intervention
Arm/Group Description
Measure Participants	12
No. patients with worst-grade toxicity 1	5 14.7%
No. patients with worst-grade toxicity 2	8 23.5%
No. patients with worst-grade toxicity 3	11 32.4%
No. patients with worst-grade toxicity 4	1 2.9%
No. patients with worst-grade toxicity 5	0 0%

3. Secondary Outcome

Title	Tumor Response as Measured by Ultrasound
Description	Progressive disease (PD): >=20% increase in sum of longest diameter (LD) of target lesion(s), taking as reference smallest sum LD recorded since treatment started. Complete response (CR): disappearance of all target lesions. Partial response (PR): >=30% decrease in sum of LD of target lesion(s), taking as reference baseline sum LD. Stable disease (SD): neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD.
Time Frame	At screening, 8 weeks and at surgery (within 14-21 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Therapeutic Intervention
Arm/Group Description	Docetaxel 75 mg/m2 IV (1-hour infusion) on day 1 of each cycle (cycle = 2 weeks) x 4 cycles
Measure Participants	18
Complete Response	5 14.7%
Progressive Disease	1 2.9%
Stable Disease	1 2.9%
Partial Response	11 32.4%

Adverse Events

Arm/Group Title	Therapeutic Intervention
Arm/Group Description	Docetaxel 75 mg/m2 IV (1-hour infusion) on day 1 of each cycle (cycle = 2 weeks) x 4 cycles
All Cause Mortality
	Therapeutic Intervention
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Therapeutic Intervention
	Affected / at Risk (%)	# Events
Total	9/32 (28.1%)
Blood and lymphatic system disorders
Anemia	1/32 (3.1%)	1
Febrile neutropenia	1/32 (3.1%)	1
Cardiac disorders
Chest Pain	3/32 (9.4%)	4
sinus tachacardia	1/32 (3.1%)	1
Endocrine disorders
hypothyroidism	1/32 (3.1%)	2
Gastrointestinal disorders
Diarrhea	2/32 (6.3%)	2
Vomiting	2/32 (6.3%)	2
nausea	2/32 (6.3%)	3
General disorders
Fatigue	4/32 (12.5%)	5
fever	2/32 (6.3%)	2
edema, arm	1/32 (3.1%)	1
Infections and infestations
Infection	6/32 (18.8%)	6
Injury, poisoning and procedural complications
bruising	1/32 (3.1%)	2
Investigations
Neutrophil count decrease	1/32 (3.1%)	1
hemoglobin increased	6/32 (18.8%)	7
alkaline phosphatase increase	1/32 (3.1%)	1
weight loss	1/32 (3.1%)	1
Metabolism and nutrition disorders
Anorexia	1/32 (3.1%)	1
Dehydration	1/32 (3.1%)	1
hyperglycemia	2/32 (6.3%)	3
hypercholesterolemia	1/32 (3.1%)	1
hypertriglyceridemia	1/32 (3.1%)	1
Musculoskeletal and connective tissue disorders
Muscle pain	1/32 (3.1%)	1
Weakness	2/32 (6.3%)	2
pain, right shoulder	1/32 (3.1%)	1
Nervous system disorders
neuropathy	2/32 (6.3%)	2
Respiratory, thoracic and mediastinal disorders
dyspnea	1/32 (3.1%)	2
pneumothorax	1/32 (3.1%)	1
cough	1/32 (3.1%)	1
Skin and subcutaneous tissue disorders
alopecia	1/32 (3.1%)	2
nail changes	1/32 (3.1%)	1
Vascular disorders
Hematoma	1/32 (3.1%)	1
hypertension	1/32 (3.1%)	2
acute vascular leak syndrome	1/32 (3.1%)	1
Other (Not Including Serious) Adverse Events
	Therapeutic Intervention
	Affected / at Risk (%)	# Events
Total	27/32 (84.4%)
Blood and lymphatic system disorders
Blood, bone marrow	2/32 (6.3%)	2
Leukocytes,	2/32 (6.3%)	2
Eye disorders
Dry eye syndrome	4/32 (12.5%)	4
Watery eye, tearing	10/32 (31.3%)	11
Gastrointestinal disorders
Constipation	2/32 (6.3%)	2
Diarrhea	3/32 (9.4%)	3
Dyspepsia, heartburn	3/32 (9.4%)	3
Nausea	3/32 (9.4%)	3
Vomiting	2/32 (6.3%)	2
General disorders
Edema	4/32 (12.5%)	7
Fatigue	22/32 (68.8%)	25
Pain - breast	5/32 (15.6%)	5
Pain, headache	4/32 (12.5%)	4
Sweating	3/32 (9.4%)	3
Immune system disorders
Allergic reaction	2/32 (6.3%)	7
Infections and infestations
Infection	10/32 (31.3%)	11
Investigations
Alkaline Phosphatase	6/32 (18.8%)	6
Hemoglobin	14/32 (43.8%)	15
Weight gain	4/32 (12.5%)	4
Weight loss	3/32 (9.4%)	5
Metabolism and nutrition disorders
ALT, SGPT	5/32 (15.6%)	5
Anorexia	3/32 (9.4%)	3
AST, SGOT	2/32 (6.3%)	2
Glucose, serum-high	7/32 (21.9%)
Potassium, serum-low	4/32 (12.5%)	4
obesity	2/32 (6.3%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	2/32 (6.3%)	2
Muscle weakness, legs	5/32 (15.6%)	8
Musculoskelatal stiffness	3/32 (9.4%)	3
Pain, bone	5/32 (15.6%)	5
Pain, extermity limb	9/32 (28.1%)	9
Nervous system disorders
Neuropathy	18/32 (56.3%)	25
Taste alteration, dysgeusia	10/32 (31.3%)	10
Psychiatric disorders
Anxiety	8/32 (25%)	10
Depression	5/32 (15.6%)	6
Insomnia	7/32 (21.9%)	7
Memory impairment	3/32 (9.4%)	3
Reproductive system and breast disorders
Irregular menses	8/32 (25%)	8
Respiratory, thoracic and mediastinal disorders
Allergic Rhinitis	2/32 (6.3%)	2
Cough	2/32 (6.3%)	3
Dsypnea	6/32 (18.8%)	6
Skin and subcutaneous tissue disorders
Alopecia	19/32 (59.4%)	23
Nail changes	17/32 (53.1%)	17
Pruritus, itching	2/32 (6.3%)	3
Skin dry	8/32 (25%)	9
Skin reaction, hand-foot	4/32 (12.5%)	6
Vascular disorders
Flushes	8/32 (25%)	9
Hemorrhage	5/32 (15.6%)	5

Limitations/Caveats

All adverse events have been included in the "other adverse event" section. They are not differentiated by causality (eg. related to disease, con-meds).

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.