TEAM II A randomised, multicentre, prospective, phase III trial investigating TEAM IIa: Neoadjuvant hormonal therapy with exemestane for three versus six months. and / or TEAM IIb: The efficacy and safety of the addition of ibandronate to adjuvant hormonal therapy in postmenopausal women with hormone receptor positive early breast cancer.

• Register: Netherlands Trial Register
• Last refreshed on: 28 April 2013
• Main ID: NTR785
• Date of registration: 27/09/2006
• Primary sponsor: TEAM II Study Group
• Public title: TEAM II A randomised, multicentre, prospective, phase III trial investigating TEAM IIa: Neoadjuvant hormonal therapy with exemestane for three versus six months. and / or TEAM IIb: The efficacy and safety of the addition of ibandronate to adjuvant hormonal therapy in postmenopausal women with hormone receptor positive early breast cancer.
• Scientific title: A randomised, multicentre, prospective, phase III trial investigating (a) Neoadjuvant hormonal therapy with exemestane for three versus six months and / or (b) The efficacy and safety of the addition of ibandronate to adjuvant hormonal therapy in postmenopausal women with hormone receptor positive early breast cancer. - TEAM II
• Date of first enrolment: 1/10/2006
• Target sample size: 2478
• Recruitment status: recruiting
• URL: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=785
• Study type: intervention
• Study design: Randomised: Yes; Masking: None; Control: Active; Group: Parallel; Type: -

Countries of recruitment

The Netherlands

Contacts

• Name: C.J.H. Velde, van de

• Name: C.J.H. Velde, van de

Key inclusion & exclusion criteria

Inclusion criteria: TEAM IIa:

1. Female patients with histologically, by core needle biopsy-proven, invasive adenocarcinoma of the breast.

2. Any tumour with a size >= 2 cm (except cT4d = inflammatory breast cancer).

3. Indication to receive adjuvant hormonal therapy according to most recent NABON guideline.

4. ER expression > 50% (PgR either positive or negative).

5. Postmenopausal women; postmenopausal defined as:

5.1 Age >= 50 and amenorrhoea for > 1 year.

5.2 Bilateral surgical oophorectomy and no HRT (any age is acceptable).

5.3 Age < 50 with natural amenorrhoea >1 year at breast cancer diagnosis (and uterus in situ).

5.4 Postmenopausal due to chemotherapy will be excluded.

5.5 In case of doubt about menopausal status, assessment of FSH, LH and estradiol has to be performed to define the menopausal status.

6. WHO performance status 0 or 1.

7. Absence of any psychological-, familial-, sociological- or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

8. Accessible for follow-up for the duration of the trial.

9. Before randomisation, patients must be capable of understanding the trial and give written informed consent according to ICH/GCP and local IRB guidelines.


TEAM IIb:

1. Histological confirmed invasive adenocarcinoma of the breast.

2. Stage I-III breast cancer.

3. Completed adequate surgical treatment.

4. (Neo)adjuvant chemotherapy, radiotherapy and / or trastuzumab are allowed.

5. Indication to receive adjuvant hormonal therapy according to most recent NABON guideline.

6. ER and / or PgR receptor positive (ER expression >= 10% and/or PgR >= 10%).

7. Known HER2 status.

8. Adequate renal- and hepatic function as assessed by laboratory testing within four weeks prior to enrolment.

8.1 Renal function;
Creatinine <= 120 µmol/L.
If limit values, the calculated creatinine clearance should be >= 30 mL/min with the Cockcroft and Gault-formula.

8.2 Hepatic function;
Total bilirubin <= 1.5 UNL

ASAT (SGOT) and ALAT (SGPT) <= 2.5 UNL

Alkaline Phosphatase <= 2.5 UNL

9. Postmenopausal women;postmenopausal defined as:

9.1 Age >= 50 and amenorrhoea for > 1 year.

9.2 Bilateral surgical oophorectomy and no HRT (any age is acceptable).

9.3 Age < 50 with natural amenorrhoea >1 year at breast cancer diagnosis (and uterus in situ).

9.4 Postmenopausal due to chemotherapy will be excluded.

9.5 In case of doubt about the menopausal status, assessment of FSH, LH and estradiol has to be performed to define the menopausal status.

10. WHO performance status 0 or 1.

11. Absence of any psychological-, familial-, sociological- or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

12. Accessible for follow-up for the duration of the trial.

13. Before randomisation, patients must be capable of understanding the trial and give written informed consent according to ICH/GCP, and local IRB guidelines.


Exclusion criteria: TEAM IIa:

1. M1 disease by clinical examination according to the NABON guideline.

2. Multicentric breast cancer (including CIS).

3. Bilateral breast cancer (including CIS).

4. cT4d tumour (inflammatory breast cancer).

5. Hormone replacement therapy during the last 12 months.

6. One of the following diseases:

6.1 Uncontrolled cardiac disease.

6.2 Psychiatric disorders preventing proper informed consent.

6.3 Concomitant malignancies within the last five years, except for adequately treated carcinoma in situ of the uterine cervix or basal squamous cell carcinoma of the skin.

6.4 Prior invasive breast cancer or CIS within the last 15 years.

6.5 Other serious illnesses that may interfere with subject compliance, adequate informed consent or determination of causality of adverse events.

7. Concurrent participation in another clinical study that may interfere with the results of the trial involving investigational agents within thirty days of treatment from this study, unless this is agreed by the Study Coordinators.

8. More than three weeks after date of histological biopsy of primary breast cancer.


TEAM IIb

1. M1 disease by clinical examination according to the NABON guideline.

2. Bilateral invasive breast cancer (including CIS).

3. Patients having shown progressive disease in TEAM IIa (preoperative hormonal treatment with exemestane).

4. One of the following diseases:

4.1 Uncontrolled cardiac disease.

4.2 Psychiatric disorders preventing proper informed consent.

4.3 Patients with untreated oesophagitis, gastric ulcers or IBD.

4.4 Concomitant malignancies within the last five years, except for adequately treated carcinoma in situ of the uterine cervix or basal squamous cell carcinoma of the skin.

4.5 Prior invasive breast cancer and / or CIS within the last 15 years.

4.6 Other serious illnesses that may interfere with subject compliance, adequate informed consent or determination of causality of adverse events.

5. History of disease with influence on bone metabolism, including:

5.1 Pagets disease of the bone.

5.2 Primary hyperparathyroidism (patients cured by surgery may be included if interval >= 1 year).

6. Hormone replacement therapy during the last 12 months.

7. Current active dental problems including dental abscess or infection of the jawbone (maxilla or mandible), or a current or prior diagnosis of osteonecrosis of the jaw requiring maxillo-facial surgery.

8. Recent (within 4 weeks of study entry) or planned dental or jaw surgery (e.g. extraction, implants). Recent dental fillings, teeth scaling and polishing or minor gingival surgery do not exclude the patient.

9. Concurrent participation in another clinical study that may interfere with the results of the trial involving investigational agents within thirty days of treatment from this study, unless this is agreed by the Study Coordinators.

10. More than 5 weeks after final surgery or after end of adjuvant chemotherapy.


Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Breast cancer

Intervention(s)

TEAM IIa:
Patients will be randomised (1:1)between three versus six months of neoadjuvant therapy with exemestane (25 mg once daily). After surgery, patients may be randomised in the adjuvant part of the study (TEAM IIb) if the adjuvant inclusion criteria are met.


TEAM IIb:
Patients will be randomised (1:1) to oral ibandronate (50 mg once daily) for three years added to standard adjuvant systemic treatment or to standard adjuvant systemic therapy only. Hormonal treatment will be according to the most recent NABON guideline. Exemestane will be used as aromatase inhibitor.

Primary Outcome(s)

TEAM IIa:

Objective response rate (immediately prior to surgery) of the primary breast tumour, assessed by palpation, which is preferably performed by the same person.


TEAM IIb:

Three years disease free survival.

Secondary Outcome(s)

TEAM IIa:

1. Objective response rate of the breast tumour by mammography (RECIST).

2. Objective response rate of the breast tumour assessed by ultrasound (RECIST).

3. Objective response rate of the breast tumour assessed by MRI (RECIST).

4. Objective response rate of the regional lymph nodes assessed by ultrasound (RECIST).

5. Pathological complete response rate of primary breast cancer.

6. Pathological complete response rate of eventually positive lymph nodes.

7. Number of patients who required a mastectomy before neoadjuvant therapy and for whom breast conserving surgery became feasible after neoadjuvant therapy (independent of actual surgical treatment received).

8. Number of patients who required a mastectomy before neoadjuvant therapy and who received breast conserving surgery after neoadjuvant therapy.

9. Determination of predictive factors able to predict clinical and pathological response.
10. Collection of tumour samples for translational research to improve diagnostics and treatment of breast cancer.


TEAM IIb:

1. Time to and rate of bone metastases as first occurrence, in patients treated with these regimens.

2. Time to and rate of bone metastases, per se, in patients treated with these regimens.

3. Time to and rate of visceral and other distant metastases in patients treated with these regimens.

4. Time to and rate of local- and locoregional recurrences in patients treated with these regimens.

5. Time to and rate of contralateral breast cancer in patients treated with these regimens.

6. Five years disease free survival.

7. Overall survival (all cause mortality and breast cancer specific mortality) in patients treated with these regimens.

8. Safety and toxicity of ibandronate in patients treated with this bisphosphonate.

9. Specific prognostic indicators for the development of bone metastases and factors that are able to predict specific benefit from ibandronate treatment in these patients using tissue micro-array and other modern techniques.

Secondary ID(s)

BOOG 2006-04

ISRCTN17633610

Source(s) of Monetary Support

Leiden University Medical Center (LUMC)