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Breast CancerPhase 3NCT00929591

SWOG-8814 Tamoxifen With or Without Combination Chemotherapy in Postmenopausal Women Who Have Undergone Surgery for Breast Cancer

A Phase 3 study testing cyclophosphamide, doxorubicin hydrochloride and endocrine therapy in people with Breast Cancer, run by SWOG Cancer Research Network.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using tamoxifen may fight breast cancer by blocking the use of estrogen by the tumor cells. Drugs used in chemotherapy, such as doxorubicin, cyclophosphamide, and fluorouracil, work in different ways to stop the growth of tumor cells… Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer
What is being tested?
cyclophosphamide, doxorubicin hydrochloride and endocrine therapy
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,558 participants
Where
No sites listed yet
Study dates
May 1989to Mar 2010
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

DISEASE CHARACTERISTICS: Histologically proven adenocarcinoma of the breast No apocrine, adenoidcystic, or squamous carcinomas or sarcomas Pathologic Stage T1-3a, pathologic N1-2 (clinical N0-1), M0: Rendered free of gross tumor at surgery Primary tumor movable with respect to chest wall Axillary nodes movable with respect to chest wall and each other No preoperative edema of the arm, peau d'orange, skin ulceration, or inflammatory lesions One or more positive lymph nodes required No positive deep mastectomy margins or clinical skin involvement (focal microscopic dermal invasion or focal microscopic dermal lymphatic involvement allowed) No evidence of metastatic disease on pretherapy studies (including chest x-ray, bone scan, and mammogram) No bilateral invasive tumors Patients who had noninvasive ductal carcinoma in situ of the opposite breast and underwent prophylactic contralateral mastectomy are eligible Hormone receptor status: Positive for estrogen and/or progesterone receptors (at least 10 fmol/mg protein or unequivocally positive immunocytochemical assay for one or both) Participation in SWOG-8854 (flow cytometry) recommended

PATIENT CHARACTERISTICS: Age: Any age Sex: Females only Menopausal status: Postmenopausal as defined by 1 or more of the following: Bilateral oophorectomy at least 2 months prior to diagnosis of breast cancer (with or without estrogen therapy following surgery) Prior hysterectomy with at least 1 ovary remaining and either over 60 years old or with a postmenopausal FSH level Natural menopause (last menstrual period at least 1 year prior to registration or 4-12 months prior to registration with a postmenopausal FSH level) Treated with postmenopausal estrogen therapy and either over 55 years old or with a postmenopausal FSH level Performance status: Not specified Hematopoietic: WBC at least 3,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no more than 1.2 x normal Alkaline phosphatase no more than 1.2 x normal SGOT or SGPT no more than 1.2 x normal Renal: Creatinine no more than 2.0 mg/dL Cardiovascular: No uncontrolled hypertension No history of ischemic heart disease or CHF Normal ejection fraction by MUGA (required only if deemed clinically necessary for assessment) Other: No medical condition that would preclude protocol therapy: No severe diabetes No active ulcer disease No significant psychiatric disease No second malignancy within 5 years except: Adequately treated nonmelanomatous skin cancer Curatively treated Stage I cervical carcinoma Pretreatment mammogram and chest x-ray completed no more than 3 months preoperatively; blood/body fluid analyses to determine eligibility completed within 14 days prior to registration; prestudy bone scan completed within 12 weeks prior to registration and/or within 4 weeks prior to surgery

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior chemotherapy Endocrine therapy: No prior hormonal therapy (except for up to 14 days of tamoxifen stopped prior to registration) Prior estrogen- and/or progesterone-containing hormone preparations for nononcologic therapy allowed, but must be discontinued prior to registration Postmenopausal estrogen therapy should be discontinued in all patients at the time of diagnosis of breast cancer Radiotherapy: Postoperative chest wall and/or regional lymph node irradiation allowed for mastectomy patients (at discretion of the physician) either prior to registration or on protocol for any of the following: Tumor greater than 5 cm in diameter 4 or more positive nodes Extranodal extension of tumor into the axillary fat No radiotherapy for any other reason in mastectomy patients Postoperative radiotherapy either prior to registration, during tamoxifen, or after completion of chemotherapy required for lumpectomy patients Radiotherapy must be completed (if it is to be given before chemotherapy) prior to registration No immediate radiotherapy after randomization to chemotherapy Surgery: Radical, modified radical, or breast-sparing surgical procedure with at least a level I and II axillary dissection and analysis of at least 6 nodes required within 12 weeks prior to registration Lumpectomy must include: Total excisional biopsy with rim of normal breast tissue Microscopically negative margins Level I and II axillary dissection Tumor no more than 5 cm in greatest diameter Clinical and mammographic examination demonstrating absence of multicentric lesions Type of surgery, number of nodes examined, number of positive nodes, and size of the primary tumor (size of the largest tumor if more than 1 mass) must be recorded

About this study

Official title: Phase III Comparison of Adjuvant Chemoendocrine Therapy With CAF and Concurrent or Delayed Tamoxifen to Tamoxifen Alone in Postmenopausal Patients With Involved Axillary Lymph Nodes and Positive Receptors

RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using tamoxifen may fight breast cancer by blocking the use of estrogen by the tumor cells. Drugs used in chemotherapy, such as doxorubicin, cyclophosphamide, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving tamoxifen alone is more effective in treating breast cancer than giving tamoxifen together with chemotherapy or after chemotherapy.

PURPOSE: This randomized phase III trial is studying giving tamoxifen with or without combination chemotherapy to compare how well they work in treating postmenopausal women who have undergone surgery for breast cancer.

Read the detailed description

OBJECTIVES: I. Compare disease-free survival and overall survival of postmenopausal women with node-positive, estrogen and/or progesterone receptor-positive adenocarcinoma of the breast randomly assigned to postoperative adjuvant treatment with long-term (5 years) tamoxifen vs. CAF (cyclophosphamide/doxorubicin/fluorouracil) plus concurrent and long-term tamoxifen vs. CAF followed by long-term tamoxifen. II. Compare the relative toxicities of these three regimens.

OUTLINE: Randomized study. All patients are randomized on Arms I, II, and III. Lumpectomy patients must receive radiotherapy on Regimen A. At the discretion of the physician, mastectomy patients may receive radiotherapy on Regimen B for a tumor greater than 5 cm in diameter, 4 or more positive nodes, or extranodal extension of the tumor into the axillary fat. Patients randomized to Arm I who are to receive radiotherapy should begin as soon as feasible postoperatively; these patients may be irradiated while receiving tamoxifen. Patients on Arms II and III who are to receive radiotherapy are treated either postoperatively prior to registration or after completion of and recovery from 6 courses of CAF. Arm I: Antiestrogen Therapy. Tamoxifen, TMX, NSC-180973. Arm II: 3-Drug Combination Chemotherapy followed by Antiestrogen Therapy. CAF: Cyclophosphamide, CTX, NSC-26271; Doxorubicin, DOX, NSC-123127; Fluorouracil, 5-FU, NSC-19893; followed by TMX. Arm III: 3-Drug Combination Chemotherapy plus Concurrent Antiestrogen Therapy. CAF; plus concurrent TMX. Regimen A: Radiotherapy. Irradiation of the breast and underlying chest wall and (optionally) of the supraclavicular area and, if indicated, the axilla, using megavoltage equipment with photon energies of up to 6 MV followed, if indicated, by a tumor bed boost using either electrons or iridium-192 (192-Ir) implants. Regimen B: Radiotherapy. Irradiation of the chest wall using either megavoltage photons via a tangential field or electrons via a direct field plus (optional) photon irradiation of the supraclavicular area and, if indicated, the axilla.

PROJECTED ACCRUAL: 350 patients will be randomized to Arm I and 530 patients each will be randomized to Arms II and III. Accrual should be completed in about 4 years, and 4 additional years will be required for follow-up.

Conditions
Breast Cancer
Being tested
cyclophosphamide, doxorubicin hydrochloride, endocrine therapy, endocrine-modulating drug therapy, fluorouracil
Keywords
stage II breast cancer, stage IIIA breast cancer
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT00929591
Study groupRoleWhat they receive
tamoxifen for five yearsActive comparatortamoxifen for five years
Receives: Drug: endocrine therapy; Drug: tamoxifen citrate; Radiation: brachytherapy; Radiation: low-LET electron therapy; Radiation: low-LET photon therapy; Radiation: radiation therapy
CAF followed by tamoxifen for five yearsExperimentalintermittent CAF X 6 courses followed by tamoxifen for five years
Receives: Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: endocrine therapy; Drug: endocrine-modulating drug therapy; Drug: fluorouracil; Drug: tamoxifen citrate; Radiation: brachytherapy; Radiation: low-LET electron therapy; Radiation: low-LET photon therapy; Radiation: radiation therapy
CAF with concurrent tamoxifen for five yearsExperimentalintermittent CAF X 6 courses with concurrent tamoxifen for five years
Receives: Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: endocrine therapy; Drug: endocrine-modulating drug therapy; Drug: fluorouracil; Drug: tamoxifen citrate; Radiation: brachytherapy; Radiation: low-LET electron therapy; Radiation: low-LET photon therapy; Radiation: radiation therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Disease-free survival

    Measured: eight years

  2. Overall survival

    Measured: eight years

  3. Toxicity/morbidity of treatment

    Measured: during treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Jun 2009 (estimated)
  2. Study startMay 1989
  3. Primary completionAug 2005
  4. Study completionMar 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
1,558 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00929591
Sponsor's protocol ID
CDR0000075692
Other IDs
U10CA032102, SWOG-8814, CAN-NCIC-MA9, CLB-9194, EST-4188, NCCTG-883051, INT-0100
Status last verified
Jan 2013
First submitted
26 Jun 2009
Last updated
24 Jan 2013
Results posted
No
Data monitoring committee
Yes

Publications

  • Hershman DL, Unger JM, Barlow WE, Hutchins LF, Martino S, Osborne CK, Livingston RB, Albain KS. Treatment quality and outcomes of African American versus white breast cancer patients: retrospective analysis of Southwest Oncology studies S8814/S8897. J Clin Oncol. 2009 May 1;27(13):2157-62. doi: 10.1200/JCO.2008.19.1163. Epub 2009 Mar 23.

    PubMed 19307504

  • Hershman D, Unger J, Barlow W, et al.: Treatment quality and outcome of African American vs. European American breast cancer patients: retrospective analysis of Southwest Oncology Group studies S8814/S8897. [Abstract] Breast Cancer Res Treat 100 (Suppl 1): A-3049, S140-1, 2006.

  • Albain KS, Green SR, Lichter AS, Hutchins LF, Wood WC, Henderson IC, Ingle JN, O'Sullivan J, Osborne CK, Martino S. Influence of patient characteristics, socioeconomic factors, geography, and systemic risk on the use of breast-sparing treatment in women enrolled in adjuvant breast cancer studies: an analysis of two intergroup trials. J Clin Oncol. 1996 Nov;14(11):3009-17. doi: 10.1200/JCO.1996.14.11.3009.

    PubMed 8918499

  • Albain K, Barlow W, Shak S, et al.: Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal, node-positive, ER-positive breast cancer (S8814, INT0100). [Abstract] Breast Cancer Res Treat 106 (1): A-10, 2007.

  • Albain K, Barlow W, O'Malley F, et al.: Concurrent (CAFT) versus sequential (CAF-T) chemohormonal therapy (cyclophosphamide, doxorubicin, 5-fluorouracil, tamoxifen) versus T alone for postmenopausal , node-positive, estrogen (ER) and/or progesterone (PgR) receptor-positive breast cancer: mature outcomes and new biologic correlates on phase III intergroup trial 0100 (SWOG-8814). [Abstract] Breast Cancer Res Treat 88 (Suppl 1): A-37, 2004.

  • Albain KS, Green SJ, Ravdin PM, et al.: Adjuvant chemohormonal therapy for primary breast cancer should be sequential instead of concurrent: initial results from intergroup trial 0100 (SWOG-8814). [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-143, 2002.

  • Albain K, Green S, Ravdin P, et al.: Overall survival after cyclophosphamide, adriamycin, 5-Fu, and tamoxifen (CAFT) is superior to T alone in postmenopausal, receptor(+), node(+) breast cancer: new findings from phase III Southwest Oncology Group intergroup trial S8814 (INT-0100). [Abstract] Proceedings of the American Society of Clinical Oncology 20: A-94, 24a, 2001.

  • Ravdin P, Green S, Albain K, et al.: Initial report of the SWOG biological correlative study of c-erB-2 expression as a predictor of outcome in a trial comparing adjuvant CAF T with tamoxifen (T) alone. [Abstract] Proceedings of the American Society of Clinical Oncology 17: A374, 97a, 1998.

  • Albain K, Green S, Osborne K, et al.: Tamoxifen (T) versus cyclophosphamide, adriamycin and 5-FU plus either concurrent or sequential T in postmenopausal, receptor(+), node(+) breast cancer: a Southwest Oncology Group phase III intergroup trial (SWOG-8814, INT-0100). [Abstract] Proceedings of the American Society of Clinical Oncology 16: A-450, 128a, 1997.

  • Pusztai L, Hoag JR, Albain KS, Barlow WE, Stemmer SM, Meisner A, Hortobagyi GN, Shak S, Rae JM, Baehner R, Sharma P, Kalinsky KM. Development and Validation of the RSClinN+ Tool to Predict Prognosis and Chemotherapy Benefit for Hormone Receptor-Positive, Node-Positive Breast Cancer. J Clin Oncol. 2025 Mar 10;43(8):919-928. doi: 10.1200/JCO-24-01507. Epub 2024 Dec 2.

    PubMed 39621968

  • Speers CW, Symmans WF, Barlow WE, Trevarton A, The S, Du L, Rae JM, Shak S, Baehner R, Sharma P, Pusztai L, Hortobagyi GN, Hayes DF, Albain KS, Godwin A, Thompson A. Evaluation of the Sensitivity to Endocrine Therapy Index and 21-Gene Breast Recurrence Score in the SWOG S8814 Trial. J Clin Oncol. 2023 Apr 1;41(10):1841-1848. doi: 10.1200/JCO.22.01499. Epub 2023 Jan 17.

    PubMed 36649570

  • Albain KS, Barlow WE, Ravdin PM, Farrar WB, Burton GV, Ketchel SJ, Cobau CD, Levine EG, Ingle JN, Pritchard KI, Lichter AS, Schneider DJ, Abeloff MD, Henderson IC, Muss HB, Green SJ, Lew D, Livingston RB, Martino S, Osborne CK; Breast Cancer Intergroup of North America. Adjuvant chemotherapy and timing of tamoxifen in postmenopausal patients with endocrine-responsive, node-positive breast cancer: a phase 3, open-label, randomised controlled trial. Lancet. 2009 Dec 19;374(9707):2055-2063. doi: 10.1016/S0140-6736(09)61523-3. Epub 2009 Dec 10.

    PubMed 20004966

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing cyclophosphamide, doxorubicin hydrochloride and endocrine therapy in people with Breast Cancer, run by SWOG Cancer Research Network.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Jan 2013. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Disease-free survival (time frame: eight years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00929591, which also lists 12 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jan 2013.

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