A trial comparing the efficacy between the two hormone drugs degarelix and triptorelin in patients having not yet entered the menopause and having not undergone surgery. Additional to each treatment the patients receive letrozole for locally advanced endocrine responsive breast cancer.

• Register: EUCTR
• Last refreshed on: 4 April 2022
• Main ID: EUCTR2012-005326-29-IT
• Date of registration: 23/09/2013
• Prospective Registration: Yes
• Primary sponsor: International Breast Cancer Study Group (IBCSG)
• Public title: A trial comparing the efficacy between the two hormone drugs degarelix and triptorelin in patients having not yet entered the menopause and having not undergone surgery. Additional to each treatment the patients receive letrozole for locally advanced endocrine responsive breast cancer.
• Scientific title: A randomized phase II trial evaluating the endocrine activity and efficacy of neoadjuvant degarelix versus triptorelin in premenopausal patients receiving letrozole for locally advanced endocrine responsive breast cancer - TREND (TRial on the Endocrine activity of Neoadjuvant Degarelix)
• Date of first enrolment: 11/11/2013
• Target sample size: 50
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-005326-29
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Italy

Contacts

• Name: IBCSG Coordinating Center
• Affiliation: International Breast Cancer Study Group (IBCSG)

• Name: IBCSG Coordinating Center
• Affiliation: International Breast Cancer Study Group (IBCSG)

Key inclusion & exclusion criteria

Inclusion criteria:
•Female gender
•Premenopausal status determined locally:
-Estradiol (E2) above 54 pg/mL (or above 198 pmol/l),measured
=14 days prior to randomization
-If estradiol (E2) is =54 pg/mL, but the patient cannot be
regarded as postmenopausal, estradiol testing should be
repeated to confirm eligibility
•Age = 18 years
•Eastern Cooperative Oncology Group Performance Status
(ECOG PS) of 0 or1.
•Histologically confirmed invasive breast cancer:
-Primary tumor greater than 2 cm diameter, measured by clinical
examination and mammography or echography (cT2-4b)
-Any N
-No evidence of metastasis (M0)
•Primary tumor must have ER and PgR >50% of the cells
•Primary tumor must be HER2 negative or not amplified
•Hematopoietic status:
-Absolute neutrophil count = 1.5 × 109/L,
-Platelet count = 100 × 109/L,
-Hemoglobin = 9 g/dL
•Hepatic status:
-Serum total bilirubin = 1.5 × upper limit of normal (ULN). In the
case of known Gilbert’s syndrome, a higher serum total bilirubin
(< 2 × ULN) is allowed
-AST and ALT = 2.5 × ULN
-Alkaline phosphatase = 2.5 × ULN
•Renal status: Creatinine = 1.5 × ULN
•Negative serum pregnancy test, within 2-weeks (preferably 7
days) prior to randomization. Pregnancy test has to be repeated
before treatment start if treatment does not start within 15
days of the previous test.
•The patient must be willing to use effective non-hormonal
contraception (barrier method – condoms, diaphragm – also in
conjunction with spermicidal jelly, or total abstinence) after the
pregnancy test and up to surgery. Oral, injectable, or implant
hormonal contraceptives or medicated IUD are not allowed.
•Prior fertility treatment is allowed but must have been stopped at
least 12 months before randomization
•The patient has completed the baseline patient-reported
symptoms questionnaire
•Written Informed Consent (IC) must be signed and dated by the
patient and the Investigator prior to randomization
•The patient has been informed of and agrees to data transfer
and handling, in accordance with national data protection
guidelines
•The patient accepts blood samples to be taken according to the
schedule in section 4.1 for the determination of the primary
endpoint
•The patient accepts to make tumor (biopsy and surgical
specimen) available for submission for central pathology review
and to conduct translational studies as part of this protocol

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
•Postmenopausal patients.
•Any hormonal treatment (either oral, injectable, implant, or
medicated IUD) in the previous 2 months.
•Presence of HER2/neu overexpression or amplification.
•Received any prior treatment for primary invasive breast cancer.
•Received any GnRH analog or SERM or AI within 12 months prior
to randomization
• Previous (less than 10 years) or current history of malignant
neoplasms, except for curatively treated:
-Basal and squamous cell carcinoma of the skin
-Carcinoma in situ of the cervix
-Carcinoma in situ of the bladder
•Diagnosis of inflammatory breast cancer
•Bilateral invasive breast cancer
•Known history of uncontrolled or symptomatic angina, clinically
significant arrhythmias, congestive heart failure, transmural
myocardial infarction uncontrolled hypertension (= 180/110),
unstable diabetes mellitus, dyspnea at rest, or chronic therapy
with oxygen
•Concurrent disease or condition that would make the subject
inappropriate for study participation or any serious medical
disorder that would interfere with the subject’s safety
•Unresolved or unstable, serious adverse events from prior
administration of another investigational drug
•Active or uncontrolled infection CTCAE v.4 grade 2 or higher
•Dementia, altered mental status, or any psychiatric condition
that would prevent the understanding or rendering of Informed
Consent
•Treatment with an investigational agent must have stopped at
least 30 days before randomization
•Pregnant or lactating women. Lactation has to stop before
randomization.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Premenopausal patients with histologically confirmed locally advanced breast cancer and with primary tumor of ER+/PgR+ and HER2 negative or not amplified.

Intervention(s)

Pharmaceutical Form: Powder for suspension for injection
INN or Proposed INN: TRIPTORELIN ACETATE
CAS Number: 140194-24-7
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 3.75-

Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: LETROZOLE
CAS Number: 112809-51-5
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-

Trade Name: Firmagon
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: DEGARELIX
CAS Number: 214766-78-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 120-

Trade Name: Firmagon
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: DEGARELIX
CAS Number: 214766-78-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 80-

Primary Outcome(s)

Primary end point(s): Time to optimal ovarian function suppression: time from first injection of degarelix or triptorelin to the first assessment of estradiol (E2) level in the range of optimal ovarian function suppression (<10 pg/mL) during the 6 cycles of neoadjuvant treatment. Data for patients who do not reach the targeted E2 level will be censored at the last E2 evaluation date.

Timepoint(s) of evaluation of this end point: E2 levels will be determined at day 1 of the first treatment cycle before the administration of the first dose of degarelix or triptorelin (baseline), and thereafter at 24 and 72 hours, 7 days and 14 days after the first injection, and on day 1 of cycles 2 to 6 before the administration of degarelix or triptorelin.

Secondary Objective: To evaluate:
- Tolerability:
- Changes of Ki-67 proliferation marker
- The Preoperative Endocrine Prognostic Index (PEPI) score
- Best overall (disease) response: defined as best response
recorded from the start of treatment across all time points until
disease progression.
- Node negative disease at surgery.
- Breast-conserving surgery (BCS) rate.
- Patient reported symptoms (PRS) outcomes.

Main Objective: To evaluate the endocrine activity of neoadjuvant letrozole plus either degarelix or triptorelin.

Secondary Outcome(s)

Secondary end point(s): To evaluate:
- Tolerability: adverse events according to CTCAE version 4
- Changes of Ki-67 proliferation marker
- The Preoperative Endocrine Prognostic Index (PEPI) score
- Best overall (disease) response: defined as best response
recorded from the start of treatment across all time points until
disease progression.
- Node negative disease at surgery
- Breast-conserving surgery (BCS) rate.
- Patient reported symptoms (PRS) outcomes.

Timepoint(s) of evaluation of this end point: Tolerability:The frequencies of AEs by type & worst grade experienced while on the neoadjuvant treatments will be summarized & tabulated by treatment arms
-Percentage change in Ki67 expression from pre-treatment to surgery (24 weeks) summarized for each treatment arm
-PEPI scores assessed at the time of surgery (24weeks) for both treatment arms
-Best overall response including complete response,partial response,stable disease&progressive disease is gathered at the end of 3rd (12weeks) & 6th (24weeks)cycle of each treatment arm
-Node negative disease at surgery(after 24weeks) descriptively summarized by treatment arm
-BCS at surgery after 24weeks
-PRS scores measured at baseline, day1 of cycle2 (8weeks) and cycle4 (16weeks) of triptorelin or degarelix administration & prior surgery

Secondary ID(s)

IBCSG_41-13

Source(s) of Monetary Support

Ferring Pharmaceuticals A/S

Ethics review

Status: Approved
Approval date: 11/09/2013
Contact:

Results

• Results available: Yes
• Date Posted: 01/04/2020
• Date Completed: 25/08/2017
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-005326-29/results