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Paclitaxel and Radiation Therapy in Treating Patients Undergoing Surgery for Stage II or Stage III Breast Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Bapsi Chak, MD, Vanderbilt-Ingram Cancer Center
ClinicalTrials.gov Identifier:
NCT00647218
First received: March 28, 2008
Last updated: October 3, 2012
Last verified: October 2012
  Purpose

RATIONALE: Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving paclitaxel and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This clinical trial is studying how well giving paclitaxel together with radiation therapy works in treating patients undergoing surgery for stage II or stage III breast cancer.


Condition Intervention
Breast Cancer
Drug: Post-operative adjuvant therapy
Drug: neoadjuvant therapy
Procedure: therapeutic surgical procedure
Radiation: Radiation therapy with concurrent Paclitaxel
Drug: Hormonal Therapy

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of Neoadjuvant Paclitaxel and Concurrent Radiation With Correlative Molecular Studies in Stage II/III Breast Cancer

Resource links provided by NLM:


Further study details as provided by Vanderbilt-Ingram Cancer Center:

Primary Outcome Measures:
  • Pathologic Complete Response Rate [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxicity paclitaxel and radiation [ Time Frame: at 18 weeks ] [ Designated as safety issue: Yes ]
  • Correlation of tumor response with local recurrence-free survival, distant disease-free survival, and overall survival [ Time Frame: at time of disease progression or death by any cause ] [ Designated as safety issue: No ]
  • Protein expression profiles as measured by mass spectrometry before and after treatment with paclitaxel [ Time Frame: Baseline and 18 weeks ] [ Designated as safety issue: No ]

Enrollment: 38
Study Start Date: February 2000
Study Completion Date: November 2004
Primary Completion Date: November 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Experimental Drug: Post-operative adjuvant therapy
Adriamycin 60 mg/m2 IV over 20 minutes and Cytoxan 600 mg/m2 IV over 1 hour will be given every three weeks for 4 cycles.
Other Name: None noted
Drug: neoadjuvant therapy
Paclitaxel 175 mg/m2 IV every 3 weeks x 3 cycles
Other Name: None noted
Procedure: therapeutic surgical procedure
Modified radical mastectomy or segmental mastectomy plus axillary dissection 6-8 weeks following completion of chemotherapy/Radiotherapy.
Other Name: None noted
Radiation: Radiation therapy with concurrent Paclitaxel
Radiation to breast 4680 cGy/26 fractions with concurrent Paclitaxel 30 mg/m2, twice per week
Other Name: None noted
Drug: Hormonal Therapy
After completion of postoperative adjuvant Adriamycin and Cytoxan, hormonal therapy should be given at the discretion of the treating physician for all post-menopausal ER and/or PR positive patients. It is also recommended for pre-menopausal patients who are ER and/or PR positive.

Detailed Description:

OBJECTIVES:

Primary

  • Evaluate the efficacy of paclitaxel and concurrent radiotherapy (as measured by pathologic response rates) in patients with stage II or III breast cancer.

Secondary

  • Evaluate the toxicities of this treatment regimen.
  • Correlate paclitaxel-induced tumor response with local recurrence-free survival, distant disease-free survival, and overall survival.
  • Evaluate protein expression profiles by mass spectrometry in biopsy material and blood specimens collected before and after treatment with paclitaxel.

OUTLINE:

  • Neoadjuvant chemotherapy: Patients receive paclitaxel IV over 3 hours on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity.
  • Chemoradiotherapy: Beginning 3-4 weeks after completion of neoadjuvant chemotherapy, patients receive paclitaxel IV over 1 hour twice weekly and undergo radiotherapy once daily, 5 days a week, for 6½ weeks.
  • Surgery: At 6-8 weeks after completion of chemoradiotherapy, patients undergo surgical resection (e.g., modified radical mastectomy or lumpectomy and axillary node dissection).
  • Adjuvant chemotherapy: Beginning 4-6 weeks after surgery, patients receive doxorubicin hydrochloride IV over 20 minutes and cyclophosphamide IV over 1 hour on day 1. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.
  • Hormonal therapy: After completion of adjuvant chemotherapy, patients with estrogen receptor- and/or progesterone receptor-positive tumor receive hormonal therapy at the discretion of the treating physician.

Patients undergo blood and tissue sample collection periodically to analyze changes in cell cycle by flow cytometry; antibody assays; kinase assays for cyclin B1/CDC2; genetic assays for p53, p21, and other molecular markers; and protein expression assays by mass spectrometry.

After completion of study therapy, patients are followed periodically.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically or cytologically documented invasive carcinoma of the breast*

    • Tumor ≥ 2 cm in greatest dimension (e.g., T2-4) and any nodal status (e.g., N0-3), including locally advanced disease, as defined by the following criteria:

      • Primary tumor ≥ 5 cm
      • Tumor of any size with direct extension to the chest wall or skin
      • Inflammatory breast cancer (T4d)
      • Metastasis to ipsilateral internal mammary node
      • Ipsilateral lymph nodes that are clinically fixed to each other or to other structures (N2) NOTE: *Diagnosis may be made by core or tru-cut biopsies
  • Measurable or evaluable tumor

    • Measurable disease is defined as any mass that can be reproducibly measured in two perpendicular dimensions
    • Evaluable disease is defined as any lesion visible by mammogram or palpable by physical exam that does not fit the above criteria of measurability
  • Planning to undergo breast conservation surgery
  • Willing to undergo AND is a candidate for radiotherapy, in the judgement of the treating radiation oncologist
  • No evidence of distant metastatic disease (e.g., lung, liver, bone, brain)
  • Hormone receptor status not specified

PATIENT CHARACTERISTICS:

  • Menopausal status not specified
  • ECOG performance status 0-1
  • WBC ≥ 3,000/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Creatinine ≤ 1.5 times upper limit of normal (ULN)
  • Bilirubin ≤ 1.5 times ULN
  • Left ventricular ejection fraction ≥ 45%
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No other malignancies within the past 5 years, except curatively treated nonmelanomatous skin cancer or carcinoma in situ of the cervix
  • No history of hypersensitivity reaction to products containing polysorbate 80 (Tween 80)
  • No serious medical illness that, in the judgment of the treating physician, places the patient at risk
  • No peripheral neuropathy ≥ grade 2

PRIOR CONCURRENT THERAPY:

  • Prior tamoxifen as chemoprevention allowed
  • No prior radiotherapy to the ipsilateral breast

    • Prior radiotherapy to the contralateral breast is allowed
  • No prior chemotherapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00647218

Locations
United States, Tennessee
Williamson Medical Center
Frankling, Tennessee, United States, 37067
Jackson-Madison Hospital
Jackson, Tennessee, United States, 38301
Boston Baskin Cancer Center
Memphis, Tennessee, United States, 38104
Methodist Lebonheur Healthcare
Memphis, Tennessee, United States, 38104
Meharry Medical College
Nashville, Tennessee, United States, 37208
Vanderbilt-Ingram Cancer Cetner
Nashville, Tennessee, United States
Sponsors and Collaborators
Vanderbilt-Ingram Cancer Center
Investigators
Study Chair: A. Bapsi Chakravarthy, MD Vanderbilt-Ingram Cancer Center
  More Information

No publications provided

Responsible Party: Bapsi Chak, MD, Associate Professor; Radiation Oncologist, Vanderbilt-Ingram Cancer Center
ClinicalTrials.gov Identifier: NCT00647218     History of Changes
Other Study ID Numbers: VCC BRE 9936, P30CA068485, VU-VICC-BRE-9936
Study First Received: March 28, 2008
Last Updated: October 3, 2012
Health Authority: United States: Federal Government

Keywords provided by Vanderbilt-Ingram Cancer Center:
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Paclitaxel
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on November 20, 2014