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Anastrozole or Tamoxifen in Treating Postmenopausal Women With Ductal Carcinoma in Situ Who Are Undergoing Lumpectomy and Radiation Therapy

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ClinicalTrials.gov Identifier: NCT00053898
Recruitment Status : Completed
First Posted : February 6, 2003
Results First Posted : March 12, 2018
Last Update Posted : March 12, 2018
Sponsor:
Collaborators:
National Cancer Institute (NCI)
North Central Cancer Treatment Group
Southwest Oncology Group
American College of Surgeons
Information provided by (Responsible Party):
NSABP Foundation Inc

Brief Summary:

RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Tamoxifen may fight breast cancer by blocking the use of estrogen. Anastrozole may fight breast cancer by decreasing estrogen production. It is not yet known whether anastrozole is more effective than tamoxifen in preventing the recurrence of breast cancer.

PURPOSE: This randomized phase III trial is studying anastrozole to see how well it works compared to tamoxifen in preventing the recurrence of breast cancer in postmenopausal women with ductal carcinoma in situ who are undergoing lumpectomy and radiation therapy.


Condition or disease Intervention/treatment Phase
Breast Cancer Drug: anastrozole Drug: tamoxifen citrate Radiation: Radiation Therapy Phase 3

Detailed Description:

OBJECTIVES:

  • Compare the value of anastrozole vs tamoxifen, in terms of preventing recurrence (i.e., local, regional, and distant recurrences and contralateral breast cancer), after lumpectomy and radiotherapy in postmenopausal women with ductal carcinoma in situ (DCIS).
  • Compare subsequent disease occurrence, in terms of invasive breast cancer (local, regional, distant, or contralateral), ipsilateral and contralateral breast cancer (invasive and DCIS), and non-breast second primary malignancies, in patients treated with these drugs.
  • Compare quality of life and symptoms of patients treated with these drugs.*
  • Compare quality-adjusted survival time of patients treated with these drugs.*
  • Compare the occurrence of osteoporotic fractures in patients treated with these drugs.
  • Compare disease-free and overall survival of patients treated with these drugs. NOTE: *The quality of life study closed to accrual as of 12/28/04.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to age (under 60 vs 60 and over). Patients are randomized to 1 of 2 treatment arms (arm I and arm II closed to accrual as of 6/15/06).

  • Arm I (closed to accrual as of 6/15/06): Patients receive oral tamoxifen and oral placebo once daily for 5 years.
  • Arm II (closed to accrual as of 6/15/06): Patients receive oral anastrozole and oral placebo once daily for 5 years.

Beginning within 8 weeks of randomization, all patients also undergo whole breast radiotherapy, unless the patient is enrolled in protocol NSABP-B-39 and randomized to the partial breast irradiation group.

Patients are followed every 6 months for 5 years, and then annually thereafter.

For patients enrolled in the quality of life study, quality of life is assessed at baseline and then every 6 months for 6 years.*

NOTE: *The quality of life study closed to accrual as of 12/28/04.

PROJECTED ACCRUAL: A total of 3,000 patients (1,500 per treatment arm) will be accrued for this study within 5 years (arm I and arm II closed to accrual as of 6/15/06).


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3104 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Clinical Trial Comparing Anastrozole With Tamoxifen in Postmenopausal Patients With Ductal Carcinoma in Situ (DCIS) Undergoing Lumpectomy With Radiation Therapy
Study Start Date : January 2003
Actual Primary Completion Date : March 2015
Actual Study Completion Date : May 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: Group 1
tamoxifen 20 mg/day and an anastrozole look-alike placebo for 5 years
Drug: tamoxifen citrate
20 mg/day and placebo for 5 years
Radiation: Radiation Therapy
Adjuvant radiation therapy
Experimental: Group 2
anastrozole, 1 mg/day and an tamoxifen look-alike placebo for 5 years
Drug: anastrozole
1 mg/day and placebo for 5 years
Radiation: Radiation Therapy
Adjuvant radiation therapy



Primary Outcome Measures :
  1. Percentage of Patients Free From Breast Cancer [ Time Frame: 10 years ]
    Percentage of patients free from breast cancer event at 10 years where events include local, regional, or distant recurrence or contralateral breast cancer, invasive or DCIS.


Secondary Outcome Measures :
  1. Percentage of Patients Free From Invasive Breast Cancer [ Time Frame: 10 years ]
    Percentage of patients free from an invasive breast cancer event where events include invasive local, regional, or distant recurrence, or contralateral breast cancer, occurring as a first cancer event. Note that this endpoint includes only invasive breast cancers and the primary endpoint includes both invasive and DCIS breast cancers.

  2. Percentage of Patients Free From Ipsilateral Recurrence [ Time Frame: 10 years ]
    Percentage of patients free from a breast cancer recurrence in the ipsilateral breast (invasive and DCIS), occurring as a first cancer event.

  3. Percentage of Patients Free From Contralateral Breast Cancer [ Time Frame: 10 years ]
    Percentage of patients free from a breast cancer recurrence in the contralateral breast (invasive and DCIS), occurring as a first cancer event.

  4. Percentage of Patients Free From Non-breast Secondary Cancer [ Time Frame: 10 years ]
    Percentage of patients free from any non-breast second primary cancer other than squamous or basal cell carcinoma of the skin, carcinoma in situ of the colon, melanoma in situ, or carcinoma in situ of the cervix, occurring as a first cancer event.

  5. Percentage of Patients Free From Osteoporotic Fractures [ Time Frame: 10 years ]
    Percentage of patients free from fractures of the hip, spine, and wrist.

  6. Percentage of Patients Alive and Disease-free [ Time Frame: 10 years ]
    Percentage of patients free from a disease-free survival event where events include any recurrence, second primary cancer, and death from any cause. Lobular carcinoma in situ (LCIS), basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the colon, melanoma in situ, and cervical carcinoma in situ will not be included as recurrences or second primary cancer.

  7. Percentage of Patients Alive (Overall Survival) [ Time Frame: 10 years ]
    Percentage of patients alive.

  8. Quality of Life [ Time Frame: 5 years ]
    The primary outcome of the QOL substudy was the Medical Outcomes Study-Short Form 12 (SF-12) physical health component scale score. The SF-12 physical score was calculated to have a range of 0-100 and was normalized to have a mean of 50 and a standard deviation of 10 in the general population. Higher scores indicate better health.

  9. Quality-adjusted Survival Time [ Time Frame: baseline and every 6 month for 6 years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed ductal carcinoma in situ (DCIS) of the breast

    • Mixed DCIS and lobular carcinoma in situ (LCIS) allowed
  • Must have undergone lumpectomy

    • Margins must be histologically free of disease
    • Re-excision to obtain tumor-free margins allowed
    • No more than 84 days since prior lumpectomy or re-excision
  • More than 1 area of DCIS allowed provided all disease is removed with tumor-free margins

    • Masses or clusters of calcification that are clinically or mammographically suspicious must be biopsied
  • No prior invasive breast cancer or DCIS

    • Patients with a history of LCIS are eligible
  • No prior or concurrent invasive (including microinvasive) breast cancer

    • DCIS "suspicious" for microinvasion allowed
  • No bilateral malignancy

    • No mass or mammographic abnormality suspicious for malignancy in the opposite breast unless not malignant as proven by biopsy
  • No Paget's disease of the nipple
  • No positive ipsilateral axillary or intramammary nodes

    • No palpable nodes in the ipsilateral or contralateral axilla or palpable supraclavicular or infraclavicular nodes unless not involved with tumor as proven by biopsy
  • Hormone receptor status:

    • Estrogen- or progesterone-receptor positive as determined by immunohistochemistry

      • Borderline results are considered positive

PATIENT CHARACTERISTICS:

Age

  • See Menopausal status

Sex:

  • Female

Menopausal status:

  • Postmenopausal as defined by at least 1 of the following:

    • Prior documented bilateral oophorectomy
    • At least 12 months without spontaneous bleeding
    • Age 55 or over with prior hysterectomy without oophorectomy
    • Age 54 or under with prior hysterectomy without oophorectomy with a documented follicle-stimulating hormone level in the postmenopausal range

Performance status

  • Zubrod 0-2

Life expectancy

  • At least 10 years (excluding diagnosis of breast cancer)

Hematopoietic

  • WBC normal

Hepatic

  • AST normal
  • Bilirubin normal
  • Alkaline phosphatase normal
  • No hepatic disease that would preclude administration of study drugs

Renal

  • Creatinine normal
  • No renal disease that would preclude administration of study drugs

Cardiovascular

  • No prior documented cerebral vascular accident or transient ischemic attack
  • No prior deep vein thrombosis
  • No cardiovascular disease that would preclude administration of study drugs
  • No uncontrolled hypertension (i.e., systolic blood pressure at least 180 mm Hg or diastolic blood pressure at least 110 mm Hg based on the average of 2 or more readings at each of 2 or more visits after initial screening)
  • No uncontrolled atrial fibrillation

Pulmonary

  • No pulmonary embolus

Other

  • Not pregnant or nursing
  • Patients with a history of non-breast malignancies are eligible provided they have been disease-free for ≥ 5 years and are deemed by their physician to be at low risk for recurrence
  • No other malignancy within the past 5 years except treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, carcinoma in situ of the colon, or melanoma in situ
  • No psychiatric or addictive disorders that would preclude informed consent
  • No uncontrolled diabetes, defined as hemoglobin A1C greater than 9% (fasting glucose 200 mg/dL)
  • No nonmalignant systemic disease that would preclude administration of study drugs

PRIOR CONCURRENT THERAPY:

Endocrine therapy

  • No prior or concurrent aromatase inhibitors (e.g., exemestane or letrozole) or tamoxifen
  • No concurrent raloxifene or other selective estrogen receptor modulators
  • No concurrent sex hormone therapy (e.g., estrogen or progesterone replacement therapy, oral contraceptives, androgens, luteinizing hormone releasing hormone analogs, prolactin inhibitors, or antiandrogens)

    • Low-dose estrogen vaginal creams or Estring allowed

Radiotherapy

  • Radiotherapy for this cancer initiated before study is allowed

Surgery

  • See Disease Characteristics
  • No prior or concurrent mastectomy for DCIS
  • Prior sentinel node biopsy or axillary node dissection allowed provided nodes are pathologically negative

Other

  • No concurrent warfarin
  • No other systemic therapy for this cancer initiated before study
  • No other concurrent anticancer therapy unless permitted by the protocol investigator
  • No concurrent participation in another clinical trial of therapy for DCIS

    • Concurrent participation in protocol NSABP-B-39 allowed

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00053898


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Sponsors and Collaborators
NSABP Foundation Inc
National Cancer Institute (NCI)
North Central Cancer Treatment Group
Southwest Oncology Group
American College of Surgeons
Investigators
Principal Investigator: Norman Wolmark, MD NSABP Foundation Inc

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: NSABP Foundation Inc
ClinicalTrials.gov Identifier: NCT00053898     History of Changes
Other Study ID Numbers: NSABP B-35
NSABP-B-35
SWOG-NSABP-B-35
NCCTG-NSABP-B-35
ACOSOG-NSABP-B-35
First Posted: February 6, 2003    Key Record Dates
Results First Posted: March 12, 2018
Last Update Posted: March 12, 2018
Last Verified: March 2018

Keywords provided by NSABP Foundation Inc:
breast cancer in situ
ductal breast carcinoma in situ

Additional relevant MeSH terms:
Carcinoma
Carcinoma in Situ
Carcinoma, Ductal
Carcinoma, Intraductal, Noninfiltrating
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Neoplasms, Ductal, Lobular, and Medullary
Breast Carcinoma In Situ
Tamoxifen
Anastrozole
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Bone Density Conservation Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action