Pegylated Liposomal Doxorubicin and Docetaxel in Treating Women With Locally Advanced Breast Cancer That Can Be Removed By Surgery

• Sponsor: Roswell Park Cancer Institute (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00524459
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 6
• Location: 1

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as liposomal doxorubicin and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) and giving them before surgery may kill more tumor cells.

PURPOSE: This phase II trial is studying the side effects of giving liposomal doxorubicin together with docetaxel before surgery and to see how well it works in treating women with locally advanced breast cancer that can be removed by surgery.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: docetaxel; Drug: pegylated liposomal doxorubicin hydrochloride; Procedure: conventional surgery; Procedure: neoadjuvant therapy	Phase 2

Detailed Description

OBJECTIVES:

Primary

• To evaluate the rate of pathological complete response and clinical complete response in women with locally advanced breast cancer treated with pegylated doxorubicin hydrochloride liposome and docetaxel.

Secondary

• To assess the overall clinical local regional response in patients treated with this preoperative chemotherapy regimen.

• To evaluate the number of patients who would have required a mastectomy upfront but who underwent breast conservation therapy instead after neoadjuvant chemotherapy.

• To assess the safety, particularly with regard to neutropenia and cardiac toxicity, of pegylated doxorubicin hydrochloride liposome and docetaxel.

OUTLINE: This is a multicenter study.

Patients receive pegylated doxorubicin hydrochloride liposome IV over 90 minutes and docetaxel IV over 90 minutes on day 1. Patients receive pegylated filgrastim subcutaneously on days 2 or 3 post-chemotherapy in courses 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Within 8 weeks after completion of chemotherapy, patients undergo a lumpectomy or mastectomy to remove the tumor. Some patients may receive additional therapy after surgery, including hormonal therapy, chemotherapy, or radiotherapy.

After completion of study therapy, patients are followed periodically for up to 5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Primary Purpose: Treatment
• Official Title: Phase II Study of Neoadjuvant Pegylated Liposomal Doxorubicin and Docetaxel in Locally Advanced Operable Breast Cancer
• Study Start Date: May 1, 2007
• Actual Primary Completion Date: Aug 1, 2008

Outcome Measures

Primary Outcome Measures

1. Pathological Complete Response [Mammogram done pre-treatment and after four and six cycles of study chemotherapy treatment.]

2. Clinical Complete Response [Surgery done after completion of six cycles of study chemotherapy treatment.]

Secondary Outcome Measures

1. Overall Clinical Local Regional Response [Mammogram done pre-treatment and after four and six cycles of study chemotherapy treatment.]

2. Number of Women Who Would Have Required a Mastectomy Upfront But Who Underwent Breast Conservation Therapy Instead After Neoadjuvant Chemotherapy [Baseline (pre-treatment) surgical assessment, and post-chemotherapy surgical outcome.]

3. Safety, in Terms of Neutropenia and Cardiac Toxicity [Every cycle during study treatment and 8 weeks post-treatment.]

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 64 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed breast cancer using core biopsies

• Locally advanced disease

• Resectable disease

• Fine needle aspiration cytology allowed and must demonstrate invasive adenocarcinoma

• No more than 8 weeks since initial cytologic or histologic diagnosis of breast cancer

• Tumor must meet the following criteria:

• Palpable on clinical examination and confined to either the breast or to the breast and ipsilateral axilla

• Measured clinically as greater than 2 cm in size (T2)

• Patients with skeletal pain are eligible if bone scan and/or roentgenological examination fail to disclose metastatic disease

• Suspicious findings must be confirmed as benign by x-ray, MRI scan, or biopsy

• Hormonal status not specified

PATIENT CHARACTERISTICS:

Inclusion criteria:

• Female

• Menopausal status not specified

• ECOG performance status 0-2

• Life expectancy ≥ 10 years

• Platelet count ≥ 100,000/mm³

• ANC ≥ 1,500/mm³

• Hemoglobin ≥ 9.0 g/dL

• Bilirubin normal

• AST or ALT normal

• Alkaline phosphatase normal

• Serum creatinine normal

• Negative pregnancy test

• Fertile patients must use effective contraception (e.g., abstinence, intrauterine device, barrier device with spermicide, or surgical sterilization) during and for 3 months after completion of study therapy

• Normal cardiac function by LVEF or MUGA scan

• Patients with prior non-breast malignancies are eligible if they have been disease-free for ≥ 10 years

• The following are allowed even if diagnosed within the past 10 years:

• Squamous or basal cell carcinoma of the skin that has been effectively treated

• Carcinoma in situ of the cervix that has been treated by operation only

• Lobular carcinoma in situ of the ipsilateral or contralateral breast treated by segmental resection only

Exclusion criteria:

• Pregnant or lactating women

• Male patients

• Hyperbilirubinemia

• Female patients with 1 or more of the following conditions:

• Ulceration, erythema, infiltration of the skin (complete fixation), or peau d'orange (edema) of any magnitude

• Tethering or dimpling of the skin or nipple inversion should not be interpreted as skin infiltration

• Ipsilateral lymph nodes that are clinically fixed to one another or to other structures (N2 disease)

• Bilateral malignancy or a mass in the opposite breast suspicious for malignancy, unless there is biopsy proof that the mass is not malignant

• Suspicious palpable nodes in the contralateral axilla or palpable supraclavicular or infraclavicular nodes, unless there is biopsy evidence that these are not involved with the tumor

• Nonmalignant systemic disease (e.g., cardiovascular, renal, or hepatic) that would preclude study therapy

• Active cardiac disease that would preclude the use of doxorubicin hydrochloride, including any of the following:

• Documented myocardial infarction

• Angina pectoris that requires the use of antianginal medication

• History of documented New York Heart Association class II-IV heart failure

• Valvular disease with documented cardiac function compromise

• Poorly controlled hypertension (i.e., diastolic BP > 100 mm Hg)

• Patients with well-controlled hypertension and on medication are eligible for study

• Psychiatric or addictive disorders that would preclude obtaining informed consent

PRIOR CONCURRENT THERAPY:

Inclusion criteria:

• Concurrent noncancer therapies allowed if used for conditions other than breast cancer

• Adjuvant therapy after surgery allowed

Exclusion criteria:

• Prior radiotherapy, chemotherapy, immunotherapy, and/or hormonal therapy for breast cancer

• Prior anthracycline therapy for any condition

• Concurrent hormonal therapy including tamoxifen, aromatase inhibitors, or raloxifene

• Concurrent sex hormonal therapy including birth-control pills or ovarian hormonal replacement therapy

• Concurrent other cancer therapy

• Concurrent herbal or alternative therapies for breast cancer

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001

Sponsors and Collaborators

• Roswell Park Cancer Institute
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Tracey O'Connor, MD, Roswell Park Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Roswell Park Cancer Institute
• ClinicalTrials.gov Identifier: NCT00524459
• Other Study ID Numbers: I 75506; RPCI-I-75506
• First Posted: Sep 3, 2007
• Last Update Posted: Aug 29, 2014
• Last Verified: Aug 1, 2014

• Keywords provided by Roswell Park Cancer Institute: stage IIIA breast cancer; stage IIIB breast cancer
• Additional relevant MeSH terms: Breast Neoplasms; Docetaxel; Doxorubicin; Liposomal doxorubicin

Study Results

Participant Flow

Arm/Group Title	DOXIL (Pegylated Liposomal Doxorubicin) and Docetaxel
Arm/Group Description	DOXIL 30 mg/m2 + Docetaxel 60 mg/m2 every 21 days x 6 cycles Pegylated Filgrastim given on day 2 or 3 post chemotherapy
Period Title: Overall Study
STARTED	6
COMPLETED	4
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	DOXIL (Pegylated Liposomal Doxorubicin) and Docetaxel
Arm/Group Description	DOXIL 30 mg/m2 + Docetaxel 60 mg/m2 every 21 days x 6 cycles Pegylated Filgrastim given on day 2 or 3 post chemotherapy
Overall Participants	6
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.5 (9.4)
Sex: Female, Male (Count of Participants)
Female	6 100%
Male	0 0%

Outcome Measures

1. Primary Outcome

Title	Pathological Complete Response
Time Frame	Mammogram done pre-treatment and after four and six cycles of study chemotherapy treatment.

Outcome Measure Data

Analysis Population Description

Due to the study's early termination and inadequate number of patients, no patients were analyzed.

Arm/Group Title	DOXIL (Pegylated Liposomal Doxorubicin) and Docetaxel
Arm/Group Description	DOXIL 30 mg/m2 + Docetaxel 60 mg/m2 every 21 days x 6 cycles Pegylated Filgrastim given on day 2 or 3 post chemotherapy
Measure Participants	0

2. Primary Outcome

Title	Clinical Complete Response
Time Frame	Surgery done after completion of six cycles of study chemotherapy treatment.

Outcome Measure Data

Analysis Population Description

Due to the study's early termination and inadequate number of patients, no patients were analyzed.

Arm/Group Title	DOXIL (Pegylated Liposomal Doxorubicin) and Docetaxel
Arm/Group Description	DOXIL 30 mg/m2 + Docetaxel 60 mg/m2 every 21 days x 6 cycles Pegylated Filgrastim given on day 2 or 3 post chemotherapy
Measure Participants	0

3. Secondary Outcome

Title	Overall Clinical Local Regional Response
Time Frame	Mammogram done pre-treatment and after four and six cycles of study chemotherapy treatment.

Outcome Measure Data

Analysis Population Description

Due to the study's early termination and inadequate number of patients, no patients were analyzed.

Arm/Group Title	DOXIL (Pegylated Liposomal Doxorubicin) and Docetaxel
Arm/Group Description	DOXIL 30 mg/m2 + Docetaxel 60 mg/m2 every 21 days x 6 cycles Pegylated Filgrastim given on day 2 or 3 post chemotherapy
Measure Participants	0

4. Secondary Outcome

Title	Number of Women Who Would Have Required a Mastectomy Upfront But Who Underwent Breast Conservation Therapy Instead After Neoadjuvant Chemotherapy
Time Frame	Baseline (pre-treatment) surgical assessment, and post-chemotherapy surgical outcome.

Outcome Measure Data

Analysis Population Description

Due to the study's early termination and inadequate number of patients, no patients were analyzed.

Arm/Group Title	DOXIL (Pegylated Liposomal Doxorubicin) and Docetaxel
Arm/Group Description	DOXIL 30 mg/m2 + Docetaxel 60 mg/m2 every 21 days x 6 cycles Pegylated Filgrastim given on day 2 or 3 post chemotherapy
Measure Participants	0

5. Secondary Outcome

Title	Safety, in Terms of Neutropenia and Cardiac Toxicity
Time Frame	Every cycle during study treatment and 8 weeks post-treatment.

Outcome Measure Data

Analysis Population Description

Due to the study's early termination and inadequate number of patients, no patients were analyzed.

Arm/Group Title	DOXIL (Pegylated Liposomal Doxorubicin) and Docetaxel
Arm/Group Description	DOXIL 30 mg/m2 + Docetaxel 60 mg/m2 every 21 days x 6 cycles Pegylated Filgrastim given on day 2 or 3 post chemotherapy
Measure Participants	0

Adverse Events

Arm/Group Title	DOXIL (Pegylated Liposomal Doxorubicin) and Docetaxel
Arm/Group Description	DOXIL 30 mg/m2 + Docetaxel 60 mg/m2 every 21 days x 6 cycles Pegylated Filgrastim given on day 2 or 3 post chemotherapy
All Cause Mortality
	DOXIL (Pegylated Liposomal Doxorubicin) and Docetaxel
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	DOXIL (Pegylated Liposomal Doxorubicin) and Docetaxel
	Affected / at Risk (%)	# Events
Total	1/6 (16.7%)
Immune system disorders
Hypersensitivity	1/6 (16.7%)	1
Other (Not Including Serious) Adverse Events
	DOXIL (Pegylated Liposomal Doxorubicin) and Docetaxel
	Affected / at Risk (%)	# Events
Total	6/6 (100%)
Blood and lymphatic system disorders
Anaemia	3/6 (50%)	3
Lymphopenia	1/6 (16.7%)	1
Neutropenia	1/6 (16.7%)	2
Eye disorders
Lacrimation increased	5/6 (83.3%)	5
Gastrointestinal disorders
Aphthous stomatitis	1/6 (16.7%)	1
Constipation	3/6 (50%)	3
Dyspepsia	4/6 (66.7%)	4
Haemorrhoids	1/6 (16.7%)	1
Nausea	5/6 (83.3%)	5
Stomatitis	4/6 (66.7%)	6
Vomiting	1/6 (16.7%)	1
General disorders
Fatigue	4/6 (66.7%)	4
Oedema peripheral	1/6 (16.7%)	1
Pyrexia	1/6 (16.7%)	1
Infections and infestations
Fungal skin infection	1/6 (16.7%)	1
Laryngitis	1/6 (16.7%)	1
Oral candidiasis	2/6 (33.3%)	2
Investigations
Alanine aminotransferase increased	3/6 (50%)	4
Aspartate aminotransferase increased	3/6 (50%)	4
Blood alkaline phosphatase increased	2/6 (33.3%)	2
Blood calcium	1/6 (16.7%)	1
Blood glucose	1/6 (16.7%)	1
Blood sodium increased	1/6 (16.7%)	1
Haemoglobin decreased	1/6 (16.7%)	1
White blood cell count decreased	2/6 (33.3%)	2
Metabolism and nutrition disorders
Decreased appetite	4/6 (66.7%)	4
Hypercalcaemia	2/6 (33.3%)	2
Hyperglycaemia	5/6 (83.3%)	14
Hyperkalaemia	2/6 (33.3%)	2
Hypernatraemia	1/6 (16.7%)	1
Hypoglycaemia	1/6 (16.7%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	2/6 (33.3%)	2
Back pain	1/6 (16.7%)	1
Bone pain	2/6 (33.3%)	2
Myalgia	1/6 (16.7%)	1
Pain in extremity	1/6 (16.7%)	1
Nervous system disorders
Dysgeusia	4/6 (66.7%)	4
Headache	4/6 (66.7%)	4
Hypoaesthesia	1/6 (16.7%)	1
Neurological symptom	1/6 (16.7%)	1
Neuropathy peripheral	1/6 (16.7%)	1
Peripheral sensory neuropathy	1/6 (16.7%)	1
Sinus headache	1/6 (16.7%)	1
Psychiatric disorders
Mood altered	1/6 (16.7%)	1
Renal and urinary disorders
Pollakiuria	1/6 (16.7%)	1
Reproductive system and breast disorders
Amenorrhoea	2/6 (33.3%)	2
Metrorrhagia	1/6 (16.7%)	1
Respiratory, thoracic and mediastinal disorders
Cough	2/6 (33.3%)	2
Dysphonia	1/6 (16.7%)	1
Dyspnoea exertional	1/6 (16.7%)	1
Oropharyngeal pain	2/6 (33.3%)	2
Rhinorrhoea	1/6 (16.7%)	1
Skin and subcutaneous tissue disorders
Alopecia	5/6 (83.3%)	7
Dermatitis allergic	1/6 (16.7%)	1
Erythema	1/6 (16.7%)	1
Heat rash	1/6 (16.7%)	1
Nail disorder	3/6 (50%)	5
Palmar-plantar erythrodysaesthesia syndrome	4/6 (66.7%)	4
Pruritus	1/6 (16.7%)	1
Rash	3/6 (50%)	5
Vascular disorders
Flushing	1/6 (16.7%)	1
Hot flush	4/6 (66.7%)	6

Limitations/Caveats

Due to the study's early termination and inadequate number of patients, no patients were analyzed.

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.