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| ID | Type | Description | Link |
|---|---|---|---|
| CAN-NCIC-MA14 | |||
| NCI-V96-1060 | |||
| CDR0000065135 | Other Identifier | PDQ |
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RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using tamoxifen with or without octreotide may fight breast cancer by blocking the uptake of estrogen. It is not yet known which treatment regimen is more effective for breast cancer.
PURPOSE: Randomized phase III trial to compare the effectiveness of tamoxifen with or without octreotide in treating postmenopausal women who have stage I, stage II, or stage III breast cancer.
OBJECTIVES: I. Compare event-free, recurrence-free, and overall survival following adjuvant therapy with tamoxifen alone vs. tamoxifen plus octreotide long-acting release formulation in postmenopausal women with stage I/II/III breast cancer. II. Compare the toxicity and quality of life associated with each treatment regimen. III. Compare the effects of each treatment regimen on insulin-like growth factor-I (IGF-I) physiology, and study the relationship between IGF-I physiology and outcome.
OUTLINE: This is a randomized study. Patients are stratified by participating institution, when and whether they receive adjuvant chemotherapy, axillary lymph node status, and hormone receptor status. All patients are randomized within 12 weeks of definitive surgery. Patients receiving adjuvant chemotherapy prior to protocol treatment are randomized within 6 weeks after the last dose of chemotherapy. One group of patients receives daily oral tamoxifen, while a second group receives daily oral tamoxifen plus octreotide (long-acting release formulation) by monthly depot injection. Treatment in both groups continues for 5 years or until disease recurrence or development of a second malignancy. Patients are followed monthly for 4 months, every 4 months for 3 years, and every 6 months thereafter.
PROJECTED ACCRUAL: A total of 850 patients will be entered over 4.2 years in this multicenter study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Octreotide | Active Comparator |
| |
| Tamoxifen | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| octreotide acetate | Drug | Octreotide LAR (SMS 201-995 pa LAR) 90 mg depot injection monthly for 2 years (plus Tamoxifen 20 mg PO daily for 5 years) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Event-free survival | 6 years |
| Measure | Description | Time Frame |
|---|---|---|
| Recurrence-free survival | 6 years | |
| Overall survival | 6 years | |
| Insulin-like growth factor measures |
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DISEASE CHARACTERISTICS: Histologically proven adenocarcinoma of the breast that is potentially curable Prior treatment with one of the following therapies required: Segmental mastectomy (lumpectomy) followed by radiotherapy Chest wall irradiation allowed only in patients with T4 dermal involvement on pathologic diagnosis Further excision or boost radiotherapy to the tumor bed recommended if microscopic disease found at mastectomy margins Total mastectomy Chest wall irradiation required if microscopic disease found at mastectomy margins Clinical stage T1-3a N0-2 M0 disease prior to surgery The following T4 features exclude: Chest wall extension Edema (including peau d'orange) Skin ulceration Satellite skin nodules confined to same breast Inflammatory carcinoma Pathologic stage T1-4 NX-2 M0 disease following surgery Eligible T4 tumors are those with dermal involvement on pathology assessment only Pathologic assessment of axillary lymph nodes required May be omitted in patients with clinical N0 status provided other entry criteria are met No bilateral breast cancer without complete resection of both sides Hormone receptor status: Estrogen and progesterone receptor status determined from primary tumor when possible by quantitative biochemical methods or immunohistochemistry Results recorded as positive or negative if immunohistochemistry used Unknown status does not exclude provided other entry criteria are met
PATIENT CHARACTERISTICS: Age: Postmenopausal Sex: Women only Menopausal status: Postmenopausal by one or more of the following: Amenorrhea lasting more than 1 year in women under 50 years of age with no prior hysterectomy No menses for 6 months prior to breast surgery in women 50 years of age and over with no prior hysterectomy Documented oophorectomy prior to breast cancer diagnosis Luteinizing hormone and follicle-stimulating hormone values diagnostic of postmenopausal status by local laboratory criteria Women 50 years of age and over with prior hysterectomy Performance status: ECOG 0-2 Life expectancy: At least 5 years Hematopoietic: WBC at least 3,000/mm3 Platelet count at least 100,000/mm3 Hepatic: (unless metastatic disease ruled out by radiologic exam) AST or ALT less than twice normal Alkaline phosphatase less than twice normal Renal: Not specified Other: No symptomatic gallbladder disease or cholecystitis No intercurrent illness that reduces life expectancy to less than 5 years No other major medical or psychiatric illness that precludes study treatment or follow-up No second malignancy within 5 years except: Adequately treated basal cell skin carcinoma Adequately treated cancer of the cervix, endometrium, colon, or thyroid Able and willing to complete quality-of-life questionnaires in English or French Illiteracy, loss of sight, or other inability to complete questionnaires does not exclude Accessible for treatment and follow-up
PRIOR CONCURRENT THERAPY: Biologic therapy: No prior biologic therapy Chemotherapy: Prior or concurrent adjuvant chemotherapy allowed at investigator's discretion Recommended regimens: CMF (cyclophosphamide/methotrexate/fluorouracil) CEF (cyclophosphamide/etoposide/fluorouracil) AC (doxorubicin/cyclophosphamide) Choice of adjuvant chemotherapy regimen defined prior to randomization if given concurrently with protocol therapy Endocrine therapy: No estrogen, progestins, or androgen therapy for a period of more than 30 days following pathologic diagnosis of breast cancer Prior tamoxifen allowed All hormonal therapy discontinued prior to randomization Radiotherapy: See Disease Characteristics Surgery: See Disease Characteristics
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| Name | Affiliation | Role |
|---|---|---|
| Michael N. Pollak, MD | Jewish General Hospital | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Duluth Clinic | Duluth | Minnesota | 55805 | United States | ||
| St. Mary's/Duluth Clinic Health System |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| Result | Ali SM, Chapman JW, Demers L, et al.: Effect of adjuvant chemotherapy on bone resorption marker beta C-telopeptide (B-CTX) in postmenopausal women. [Abstract] J Clin Oncol 27 (Suppl 15): A-594, 2009. | ||
| Result | Piura E, Chapman JW, Lipton A, et al.: Serum 1-OH vitamin D (D) and prognosis of postmenopausal breast cancer (BC) patients: NCIC-CTG MA14 trial. [Abstract] J Clin Oncol 27 (Suppl 15): A-534, 2009. | ||
| Result | Pollak MN, Chapman JW, Pritchard KI, et al.: NCIC-CTG MA14 trial: tamoxifen (tam) vs. tam + octreotide (oct) for adjuvant treatment of stage I or II postmenopausal breast cancer. [Abstract] J Clin Oncol 26 (Suppl 15): A-532, 2008. | ||
| Result | Pollak MN, Chapman JW, Shepherd L, et al.: Insulin resistance, estimated by serum C-peptide level, is associated with reduced event-free survival for postmenopausal women in NCIC CTG MA.14 adjuvant breast cancer trial. [Abstract] J Clin Oncol 24 (Suppl 18): A-524, 2006. | ||
| Result | Pollak M, Pritchard K, Whelan T, et al.: The NCIC CTG MA.14 experience with the gallbladder toxicity of octreotide pamoate (oncolar) in a postmenopausal patient population undergoing adjuvant treatment for stage 1-3 breast cancer. Eur J Cancer 38(suppl 3): s2-s179, 2002. | ||
| 26728744 |
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| tamoxifen citrate | Drug | 20 mg PO for 5 years |
|
| 6 years |
| Quality of Life | 6 years |
| Duluth |
| Minnesota |
| 55805 |
| United States |
| British Columbia Cancer Agency - Fraser Valley Cancer Centre | Surrey | British Columbia | V3V 1Z2 | Canada |
| BC Cancer Agency | Vancouver | British Columbia | V5Z 4E6 | Canada |
| British Columbia Cancer Agency - Vancouver Island Cancer Centre | Victoria | British Columbia | V8R 1J8 | Canada |
| CancerCare Manitoba | Winnipeg | Manitoba | R3E 0V9 | Canada |
| Nova Scotia Cancer Centre | Halifax | Nova Scotia | B3H 1V7 | Canada |
| Royal Victoria Hospital, Barrie | Barrie | Ontario | L4M 6M2 | Canada |
| Northeastern Ontario Regional Cancer Centre, Sudbury | Greater Sudbury | Ontario | P3E 5J1 | Canada |
| Cancer Care Ontario-Hamilton Regional Cancer Centre | Hamilton | Ontario | L8V 5C2 | Canada |
| Kingston Regional Cancer Centre | Kingston | Ontario | K7L 5P9 | Canada |
| Cancer Care Ontario-London Regional Cancer Centre | London | Ontario | N6A 4L6 | Canada |
| Trillium Health Centre | Mississauga | Ontario | L5B 1B8 | Canada |
| Credit Valley Hospital | Mississauga | Ontario | L5M 2N1 | Canada |
| North York General Hospital, Ontario | North York | Ontario | M2E 1K1 | Canada |
| Lakeridge Health Oshawa | Oshawa | Ontario | L1G 2B9 | Canada |
| Ottawa Regional Cancer Center - General Division | Ottawa | Ontario | K1H 8L6 | Canada |
| Ottawa Regional Cancer Centre - Civic Campus | Ottawa | Ontario | K1Y 4K7 | Canada |
| Algoma District Medical Group | Sault Ste. Marie | Ontario | P6B 1Y5 | Canada |
| Hotel Dieu Hospital - St. Catharines | St. Catharines | Ontario | L2R 5K3 | Canada |
| Northwestern Ontario Regional Cancer Centre, Thunder Bay | Thunder Bay | Ontario | P7A 7T1 | Canada |
| Toronto East General Hospital | Toronto | Ontario | M4C 3E7 | Canada |
| Toronto Sunnybrook Regional Cancer Centre | Toronto | Ontario | M4N 3M5 | Canada |
| St. Michael's Hospital - Toronto | Toronto | Ontario | M5B 1W8 | Canada |
| Mount Sinai Hospital - Toronto | Toronto | Ontario | M5G 1X5 | Canada |
| Toronto General Hospital | Toronto | Ontario | M5G 2C4 | Canada |
| Princess Margaret Hospital | Toronto | Ontario | M5G 2M9 | Canada |
| Women's College Campus, Sunnybrook and Women's College Health Science Center | Toronto | Ontario | M5S 1B6 | Canada |
| Saint Joseph's Health Centre - Toronto | Toronto | Ontario | M6R 1B5 | Canada |
| Humber River Regional Hospital | Weston | Ontario | M9N 1N8 | Canada |
| Cancer Care Ontario - Windsor Regional Cancer Centre | Windsor | Ontario | N8W 2X3 | Canada |
| Queen Elizabeth Hospital, PEI | Charlottetown | Prince Edward Island | C1A 8T5 | Canada |
| Centre Universitaire de Sante de l'Estrie - Site Fleurimont | Fleurimont | Quebec | J1H 5N4 | Canada |
| Centre Hospitalier de l'Universite de Montreal | Montreal | Quebec | H2L-4M1 | Canada |
| McGill University Department of Oncology | Montreal | Quebec | H2W 1S6 | Canada |
| Centre Hospitalier de l'Universite' de Montreal | Montreal | Quebec | H2W 1T8 | Canada |
| Hotel Dieu de Montreal | Montreal | Quebec | H2W 1T8 | Canada |
| Hopital du Saint-Sacrament, Quebec | Québec | Quebec | G1S 4L8 | Canada |
| L'Hopital Laval | Ste-Foy | Quebec | G1V 4G5 | Canada |
| Allan Blair Cancer Centre | Regina | Saskatchewan | S4T 7T1 | Canada |
| Derived |
| Sgroi DC, Chapman JA, Badovinac-Crnjevic T, Zarella E, Binns S, Zhang Y, Schnabel CA, Erlander MG, Pritchard KI, Han L, Shepherd LE, Goss PE, Pollak M. Assessment of the prognostic and predictive utility of the Breast Cancer Index (BCI): an NCIC CTG MA.14 study. Breast Cancer Res. 2016 Jan 4;18(1):1. doi: 10.1186/s13058-015-0660-6. |
| 26276354 | Derived | Chapman JA, Costantino JP, Dong B, Margolese RG, Pritchard KI, Shepherd LE, Gelmon KA, Wolmark N, Pollak MN. Octreotide LAR and tamoxifen versus tamoxifen in phase III randomize early breast cancer trials: NCIC CTG MA.14 and NSABP B-29. Breast Cancer Res Treat. 2015 Sep;153(2):353-60. doi: 10.1007/s10549-015-3547-4. Epub 2015 Aug 15. |
| 24451146 | Derived | Bramwell VH, Tuck AB, Chapman JA, Anborgh PH, Postenka CO, Al-Katib W, Shepherd LE, Han L, Wilson CF, Pritchard KI, Pollak MN, Chambers AF. Assessment of osteopontin in early breast cancer: correlative study in a randomised clinical trial. Breast Cancer Res. 2014 Jan 22;16(1):R8. doi: 10.1186/bcr3600. |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| D015282 | Octreotide |
| D013629 | Tamoxifen |
| ID | Term |
|---|---|
| D010456 | Peptides, Cyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D013267 | Stilbenes |
| D001597 | Benzylidene Compounds |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
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