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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00022516




Registration number
NCT00022516
Ethics application status
Date submitted
10/08/2001
Date registered
27/01/2003
Date last updated
16/09/2016

Titles & IDs
Public title
Low-dose Oral Cyclophosphamide and Methotrexate Maintenance for Hormone Receptor-negative Early Breast Cancer
Scientific title
Low-dose Cytotoxics as "Anti-angiogenesis Treatment" Following Adjuvant Induction Chemotherapy for Patients With ER-negative and PgR-negative Breast Cancer
Secondary ID [1] 0 0
IBCSG-22-00
Secondary ID [2] 0 0
CDR0000068827
Universal Trial Number (UTN)
Trial acronym
22-00
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Methotrexate

No intervention: No-CM - No further chemotherapy following standard adjuvant chemotherapy.

Experimental: CM-Maintenance - 12-month CM-maintenance regimen (C, cyclophosphamide 50 mg/day orally continuously and M, methotrexate 2.5 mg twice/day orally days 1 and 2 of every week for 1 year)


Treatment: Drugs: Cyclophosphamide
50 mg/day orally continuously for 1 year

Treatment: Drugs: Methotrexate
2.5 mg twice/day orally days 1 and 2 of every week for 1 year
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Disease-free Survival
Timepoint [1] 0 0
5-year estimates, reported at a median follow-up of 6.9 years
Secondary outcome [1] 0 0
Overall Survival
Timepoint [1] 0 0
5-year estimates, reported at a median follow-up of 6.9 years
Secondary outcome [2] 0 0
Distant Recurrence-free Interval
Timepoint [2] 0 0
5-year estimates, reported at a median follow-up of 6.9 years
Secondary outcome [3] 0 0
Breast Cancer-free Interval
Timepoint [3] 0 0
5-year estimates, reported at a median follow-up of 6.9 years

Eligibility
Key inclusion criteria
DISEASE CHARACTERISTICS:

* Histologically confirmed stage I, II, or III breast cancer

* T1-3, N0-2, M0

* Patients with sentinel node biopsy positive disease must have undergone axillary dissection
* Tumor must be confined to the breast without detected metastases elsewhere
* T4 disease with minimal dermal invasion allowed
* No T4 disease with ulceration of skin, infiltration of skin (except pathologically minimal dermal involvement), peau d'orange, or inflammatory breast cancer
* No bilateral breast cancer (except in situ carcinoma) or suspicious mass in opposite breast that has not been proven benign
* No distant metastases

* No skeletal pain of unknown cause, elevated alkaline phosphatase, or bone scan showing hot spots that cannot be ruled out as metastases by x-ray, MRI, and/or CT
* Must have undergone prior total mastectomy OR breast-conserving procedure (e.g., lumpectomy, quadrantectomy, or partial mastectomy with negative margins) with radiotherapy planned

* Patients must begin or have begun an approved induction chemotherapy regimen within 8 weeks after definitive surgery
* Negative surgical margins
* Axillary clearance with at least 6 lymph nodes examined OR negative sentinel node biopsy
* Known HER2 status by immunohistochemistry or fluorescence in situ hybridization
* Hormone receptor status:

* Estrogen and progesterone receptor negative

* Less than 10% positive tumor cells by immunohistochemistry

PATIENT CHARACTERISTICS:

Age:

* Not specified

Sex:

* Not specified

Menopausal status:

* Premenopausal, defined as less than 6 months since last menstrual period (LMP) AND no prior bilateral ovariectomy AND not on estrogen replacement (OR under age 50) OR
* Postmenopausal, defined as prior bilateral ovariectomy OR more than 12 months since LMP without prior hysterectomy (OR age 50 and over)

Performance status:

* Not specified

Life expectancy:

* Not specified

Hematopoietic:

* WBC greater than 3,000/mm3
* Platelet count greater than 100,000/mm3

Hepatic:

* See Disease Characteristics
* Bilirubin less than 2.0 mg/dL
* ALT less than 1.5 times upper limit of normal OR AST less than 60 IU/L

Renal:

* Creatinine less than 1.2 mg/dL

Other:

* Not pregnant or lactating within the past 6 months
* Fertile patients must use effective barrier contraception
* No other prior or concurrent malignancy except adequately treated basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or contralateral or ipsilateral in situ breast carcinoma
* No psychiatric or addictive disorders that would preclude study
* No non-malignant systemic disease that would preclude study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Prior trastuzumab (Herceptin) allowed

Chemotherapy:

* See Disease Characteristics
* No prior adjuvant or neoadjuvant chemotherapy for breast cancer

Endocrine therapy:

* No prior endocrine therapy for breast cancer or prevention
* No prior tamoxifen or raloxifene for breast cancer

Radiotherapy:

* No prior radiotherapy for breast cancer except primary irradiation

Surgery:

* See Disease Characteristics

Other:

* No prior preventative therapy for breast cancer
Minimum age
18 Years
Maximum age
120 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/11/2000
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/08/2016
Sample size
Target
Accrual to date
Final
1086
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Tweed Heads Hospital - Tweed Heads
Recruitment hospital [2] 0 0
Queen Elizabeth Hospital - Adelaide
Recruitment hospital [3] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [4] 0 0
Maroondah Hospital - East Ringwood
Recruitment hospital [5] 0 0
Murray Valley Private Hospital and Cancer Treatment Centre - Wodonga
Recruitment hospital [6] 0 0
Christchurch Hospital - Christchurch
Recruitment postcode(s) [1] 0 0
2485 - Tweed Heads
Recruitment postcode(s) [2] 0 0
5011 - Adelaide
Recruitment postcode(s) [3] 0 0
3128 - Box Hill
Recruitment postcode(s) [4] 0 0
3135 - East Ringwood
Recruitment postcode(s) [5] 0 0
3690 - Wodonga
Recruitment postcode(s) [6] 0 0
1 - Christchurch
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Liege
Country [2] 0 0
Brazil
State/province [2] 0 0
Rio Grande do Sul
Country [3] 0 0
Chile
State/province [3] 0 0
Santiago
Country [4] 0 0
Chile
State/province [4] 0 0
Valparaiso
Country [5] 0 0
Hungary
State/province [5] 0 0
Budapest
Country [6] 0 0
Italy
State/province [6] 0 0
Bergamo
Country [7] 0 0
Italy
State/province [7] 0 0
Biella
Country [8] 0 0
Italy
State/province [8] 0 0
Carpi
Country [9] 0 0
Italy
State/province [9] 0 0
Lecco
Country [10] 0 0
Italy
State/province [10] 0 0
Milano
Country [11] 0 0
Italy
State/province [11] 0 0
Milan
Country [12] 0 0
Italy
State/province [12] 0 0
Padova
Country [13] 0 0
Italy
State/province [13] 0 0
Rimini
Country [14] 0 0
Italy
State/province [14] 0 0
Rome
Country [15] 0 0
Italy
State/province [15] 0 0
Udine
Country [16] 0 0
Nigeria
State/province [16] 0 0
Ibadan
Country [17] 0 0
Peru
State/province [17] 0 0
Lima
Country [18] 0 0
Romania
State/province [18] 0 0
Cluj-Napoca
Country [19] 0 0
South Africa
State/province [19] 0 0
Johannesburg
Country [20] 0 0
Switzerland
State/province [20] 0 0
Aarau
Country [21] 0 0
Switzerland
State/province [21] 0 0
Bellinzona
Country [22] 0 0
Switzerland
State/province [22] 0 0
Bern
Country [23] 0 0
Switzerland
State/province [23] 0 0
Chur
Country [24] 0 0
Switzerland
State/province [24] 0 0
Rheinfelden
Country [25] 0 0
Switzerland
State/province [25] 0 0
St. Gallen
Country [26] 0 0
Switzerland
State/province [26] 0 0
Thun
Country [27] 0 0
Switzerland
State/province [27] 0 0
Zurich

Funding & Sponsors
Primary sponsor type
Other
Name
ETOP IBCSG Partners Foundation
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This randomized, phase III trial was designed to test the efficacy of a low-dose chemotherapy-maintenance regimen, hypothesized to have anti-angiogenic activity, administered following standard chemotherapy in patients with early breast cancer whose tumors are hormone receptor negative.
Trial website
https://clinicaltrials.gov/study/NCT00022516
Trial related presentations / publications
Colleoni M, Gray KP, Gelber S, Lang I, Thurlimann B, Gianni L, Abdi EA, Gomez HL, Linderholm BK, Puglisi F, Tondini C, Kralidis E, Eniu A, Cagossi K, Rauch D, Chirgwin J, Gelber RD, Regan MM, Coates AS, Price KN, Viale G, Goldhirsch A. Low-Dose Oral Cyclophosphamide and Methotrexate Maintenance for Hormone Receptor-Negative Early Breast Cancer: International Breast Cancer Study Group Trial 22-00. J Clin Oncol. 2016 Oct 1;34(28):3400-8. doi: 10.1200/JCO.2015.65.6595. Epub 2016 Jun 20.
Pruneri G, Gray KP, Vingiani A, Viale G, Curigliano G, Criscitiello C, Lang I, Ruhstaller T, Gianni L, Goldhirsch A, Kammler R, Price KN, Cancello G, Munzone E, Gelber RD, Regan MM, Colleoni M. Tumor-infiltrating lymphocytes (TILs) are a powerful prognostic marker in patients with triple-negative breast cancer enrolled in the IBCSG phase III randomized clinical trial 22-00. Breast Cancer Res Treat. 2016 Jul;158(2):323-31. doi: 10.1007/s10549-016-3863-3. Epub 2016 Jul 2.
Public notes

Contacts
Principal investigator
Name 0 0
Marco Colleoni, MD
Address 0 0
European Institute of Oncology
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00022516