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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02308085




Registration number
NCT02308085
Ethics application status
Date submitted
21/11/2014
Date registered
4/12/2014
Date last updated
19/03/2020

Titles & IDs
Public title
Pregnancy Outcome and Safety of Interrupting Therapy for Women With Endocrine Responsive Breast Cancer
Scientific title
A Study Evaluating the Pregnancy Outcomes and Safety of Interrupting Endocrine Therapy for Young Women With Endocrine Responsive Breast Cancer Who Desire Pregnancy
Secondary ID [1] 0 0
Alliance A221405
Secondary ID [2] 0 0
IBCSG 48-14 / BIG 8-13
Universal Trial Number (UTN)
Trial acronym
POSITIVE
Linked study record

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Endocrine therapy interruption

Experimental: Endocrine therapy interruption - Endocrine therapy interruption after having completed between = 18 months and = 30 months.


Other interventions: Endocrine therapy interruption
3 months wash-out between treatment interruption and pregnancy attempt. Up to 2 years interruption to allow pregnancy, delivery, breastfeeding or failure to conceive.
Endocrine therapy resumption. Completion of full duration of endocrine therapy according to individual risk, institutional policy or patient's preference.

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Breast Cancer free interval (BCFI) - Kaplan-Meier Analysis
Timepoint [1] 0 0
From enrollment until the first invasive BC event, assessed up to 14 years
Secondary outcome [1] 0 0
Information on Menstruation recovery and pattern - Menstrual diary
Timepoint [1] 0 0
Up to 24 months after enrollment
Secondary outcome [2] 0 0
Pregnancy rate (determined by pregnancy test) - Pregnancy test
Timepoint [2] 0 0
Up to 24 months after enrollment
Secondary outcome [3] 0 0
Pregnancy outcome - Labor and delivery Information, full term pregnancy, caesarean section, abortion, miscarriage, ectopic, stillbirth rates.
Timepoint [3] 0 0
Up to 33 months after enrollment
Secondary outcome [4] 0 0
Offspring outcome - Collect information on preterm birth, low birth weight, births defects rates.
Timepoint [4] 0 0
Up to 33 months after enrollment
Secondary outcome [5] 0 0
Breastfeeding pattern - Analysis of pattern e.g Duration, use of ipsilateral breast if previous breast conservation, side exclusivity
Timepoint [5] 0 0
Up to 36 months after enrollment
Secondary outcome [6] 0 0
Use of assisted reproductive Technology (ART) - ART use will be tabulated
Timepoint [6] 0 0
Up to 24 months after enrollment
Secondary outcome [7] 0 0
Distant recurrence-free interval (DRFI) - Kaplan-Meier Analysis
Timepoint [7] 0 0
Time from enrollment in the study to the first breast cancer recurrence in a distant site, assessed up to 14 years

Eligibility
Key inclusion criteria
- Age = 18 and = 42 years at enrollment.

- Has received adjuvant endocrine therapy (SERM alone, GnRH analogue plus SERM or AI)
for =18 months but =30 months for early breast cancer.

Note: Patients who have received neo/adjuvant endocrine treatment within a clinical trial
and patients who have received pharmaco-prevention are eligible.

- The adjuvant endocrine therapy must have stopped within 1 month prior to enrollment.

- Patient wishes to become pregnant. Note: Patients who have undergone
oocyte/embryo/ovarian tissue cryopreservation at breast cancer diagnosis and/or have a
previous history of assisted reproductive technology (ART) are eligible.

- Breast cancer for which patient is receiving endocrine therapy must have been
histologically-proven stage I-III, endocrine-responsive (i.e., estrogen and/or
progesterone receptor positive, according to local definition of positive, determined
using immunohistochemistry (IHC)), and treated with curative intent.

Note:

- Patients with synchronous bilateral invasive breast cancer (diagnosed histologically
within 2 months) are eligible.

- Patient with invasive breast cancer or synchronous bilateral invasive breast cancer
(diagnosed histologically within 2 months) during pregnancy are eligible.

- Patients with BRCA1/2 mutations are eligible.

- Patients could have received neo/adjuvant chemotherapy, or other systemic therapy
(e.g., neo/adjuvant HER2-targeted therapy) according to institutional policy and
patient's desire.

- Patient must be premenopausal at breast cancer diagnosis, as determined locally and
documented in patient record.

- Patient must be without clinical evidence of loco-regional and distant disease, as
evaluated according to institutional assessment standards and documented in the
patient record.

- Written informed consent (IC) for trial participation must be signed and dated by the
patient and the investigator prior to enrollment.

- Written consent to biological material submission, indicating the patient has been
informed of and agrees to tissue and blood material use, transfer and handling, must
be signed and dated by the patient and the investigator prior to any procedures
specific for this trial.

- The patient has been informed of and agrees to data transfer and handling, in
accordance with national data protection guidelines.

- Patient must be accessible for follow-up.
Minimum age
18 Years
Maximum age
42 Years
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
- Post-menopausal patients at BC diagnosis, as determined locally.

- History of hysterectomy, bilateral oophorectomy or ovarian irradiation.

- Patients with current local, loco-regional relapse and/or distant metastatic breast
cancer.

- Patients with a history of prior (ipsi- and/or contralateral) invasive BC.

- Patients with previous or concomitant non-breast invasive malignancy.

- Exceptions are limited exclusively to patients with the following previous
malignancies, if adequately treated: basal or squamous cell carcinoma of the skin, in
situ non-breast carcinoma, contra- or ipsilateral in situ breast carcinoma, stage Ia
carcinoma of the cervix.

- Concurrent disease or condition that would make the patient inappropriate for study
participation or any serious medical disorder that would interfere with the patient's
safety.

- Patients with a history of noncompliance to medical treatments and/or considered
potentially unreliable.

- Patients with psychiatric, addictive, or any disorder that would prevent compliance
with protocol requirements.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
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
Single group
Other design features
Phase
Not Applicable
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
St John of God Subiaco Hospital - Perth
Recruitment postcode(s) [1] 0 0
6008 - Perth
Recruitment outside Australia
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Zurich
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Switzerland
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Zürich

Funding & Sponsors
Primary sponsor type
Other
Name
International Breast Cancer Study Group
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Alliance for Clinical Trials in Oncology
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Canadian Cancer Trials Group
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Breast International Group
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The best available evidence suggests that pregnancy after breast cancer does not increase a
woman's risk of developing a recurrence from her breast cancer. In particular, the most
recent data suggest that this is the case also in women with a hormone receptor-positive
breast cancer. There is also no indication of increased risk for delivery complications or
for the newborn. The aim of the study is to investigate if temporary interruption of
endocrine therapy, with the goal to permit pregnancy, is associated with a higher risk of
breast cancer recurrence.The study aims also to evaluate different specific indicators
related to fertility, pregnancy and breast cancer biology in young women. A
psycho-oncological companion study on fertility concerns, psychological well-being and
decisional conflicts will be conducted in interested Centers.
Trial website
https://clinicaltrials.gov/show/NCT02308085
Trial related presentations / publications
Brinton LA, Sherman ME, Carreon JD, Anderson WF. Recent trends in breast cancer among younger women in the United States. J Natl Cancer Inst. 2008 Nov 19;100(22):1643-8. doi: 10.1093/jnci/djn344. Epub 2008 Nov 11.
Leclère B, Molinié F, Trétarre B, Stracci F, Daubisse-Marliac L, Colonna M; GRELL Working Group. Trends in incidence of breast cancer among women under 40 in seven European countries: a GRELL cooperative study. Cancer Epidemiol. 2013 Oct;37(5):544-9. doi: 10.1016/j.canep.2013.05.001. Epub 2013 Jun 12. Erratum in: Cancer Epidemiol. 2014 Feb;38(1):106. GRELL Working Group [added]; multiple investigator names added.
Bentzon N, Düring M, Rasmussen BB, Mouridsen H, Kroman N. Prognostic effect of estrogen receptor status across age in primary breast cancer. Int J Cancer. 2008 Mar 1;122(5):1089-94.
Anders CK, Hsu DS, Broadwater G, Acharya CR, Foekens JA, Zhang Y, Wang Y, Marcom PK, Marks JR, Febbo PG, Nevins JR, Potti A, Blackwell KL. Young age at diagnosis correlates with worse prognosis and defines a subset of breast cancers with shared patterns of gene expression. J Clin Oncol. 2008 Jul 10;26(20):3324-30. doi: 10.1200/JCO.2007.14.2471. Erratum in: J Clin Oncol. 2011 Sep 20;29(27):3721.
Public notes

Contacts
Principal investigator
Name 0 0
Olivia Pagani, MD
Address 0 0
Oncology Institue of Southern Switzerland (IOSI)
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
Other publications