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TRial on the Endocrine Activity of Neoadjuvant Degarelix (TREND)

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ClinicalTrials.gov Identifier: NCT02005887
Recruitment Status : Completed
First Posted : December 9, 2013
Results First Posted : May 29, 2019
Last Update Posted : May 29, 2019
Sponsor:
Information provided by (Responsible Party):
International Breast Cancer Study Group

Brief Summary:
The purpose of the this study is to investigate the anti-tumor activity and tolerability of the study medications Degarelix and Triptorelin in premenopausal women receiving preoperative treatment with Letrozole.

Condition or disease Intervention/treatment Phase
Breast Cancer Invasive Nos Drug: triptorelin Drug: degarelix Drug: letrozole Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 51 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase II Trial Evaluating the Endocrine Activity and Efficacy of Neoadjuvant Degarelix Versus Triptorelin in Premenopausal Patients Receiving Letrozole for Primary Endocrine Responsive Breast Cancer
Actual Study Start Date : February 2014
Actual Primary Completion Date : August 25, 2017
Actual Study Completion Date : August 25, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: triptorelin + letrozole
Arm A: Triptorelin 3.75 mg i.m. on day 1 every 28 days for 6 cycles + letrozole 2.5 mg/day orally for 6 cycles
Drug: triptorelin
Triptorelin 3.75 mg injected into the muscle on day 1 every 28 days for 6 cycles (1 cycle= 28 days)
Other Name: decapeptyl

Drug: letrozole
Letrozole 2.5 mg orally every day for 6 cycles
Other Name: femara

Experimental: degarelix + letrozole
Arm B: Degarelix 240 mg s.c. on day 1 of cycle 1, followed by 80 mg s.c. on day 1 of cycles 2 to 6 + letrozole 2.5 mg every day orally for 6 cycles
Drug: degarelix
Degarelix 240 mg injected under the skin given as two injections of 120 mg on the first day of treatment, followed by injection of 80 mg on day 1 of cycles 2 to 6 (1 cycle=28 days)
Other Name: firmagon

Drug: letrozole
Letrozole 2.5 mg orally every day for 6 cycles
Other Name: femara




Primary Outcome Measures :
  1. Time to Optimal Ovarian Function Suppression [ Time Frame: up to 24 weeks ]
    Time from the first injection of degarelix or triptorelin to the first assessment of centrally assessed 17-β-estradiol (E2) level in the range of optimal ovarian function suppression (≤2.72 pg/mL or ≤10 pmol/L) during the 6 cycles of neoadjuvant treatments.


Secondary Outcome Measures :
  1. Ki67 Proliferation Marker Changes [ Time Frame: Before day1 of cycle 1 and surgery ]
    The percent change in Ki67 expression from pre-treatment diagnostic (baseline) biopsy to surgery, calculated as (surgery-baseline)/baseline*100.

  2. Preoperative Endocrine Prognostic Index (PEPI) Score [ Time Frame: After 24 weeks or the time of surgery ]
    Preoperative Endocrine Prognostic Index (PEPI) is the sum of the risk points (tumor size, nodal status, Ki67 level, ER status) with a 0-12 score representing the best prognostic feature (0 being the best score; 12 being the worst score), as previously determined to be associated with recurrence-free survival.

  3. Best Overall (Disease) Response [ Time Frame: From day 1 of cycle 1 across all time points until disease progression ]
    Based on WHO tumor measurement and response criteria [1], measured from the start of treatment across all time points until disease progression or the end of 6 cycles of neoadjuvant therapies, whichever comes first. Response was determined by the IBCSG Head of Medical Affairs. An internal review (IR) form was created to record the final determination on best overall response. Confirmation of partial or complete response by an additional scan was not required in this trial. Best overall response was assessed based on changes in tumor size from baseline to the assessments after 3 and after 6 cycles (denoted as day 1 of cycle 4 and prior to surgery respectively) as measured physically by caliper or ruler and as measured by breast tumor imaging (i.e., bilateral mammography and breast ultrasound).

  4. Percentage of Patients With Node-negative Disease at Surgery [ Time Frame: During surgery, an average of 2 hours ]
    The number of lymph nodes assessed at surgery minus the number of positives nodes identified, equal to zero.

  5. Percentage of Patients Who Underwent Breast-Conserving Surgery (BCS) [ Time Frame: During surgery, an average of 2 hours ]
    Whether or not patient undergoes BCS (per Surgery form).

  6. Patient-reported Symptoms (PRS) Outcomes [ Time Frame: At baseline, day 1 of cycle 2 and cycle 4 and prior to surgery; cycle 4 reported ]
    The patient-reported symptoms (PRS) will be assessed using the Functional Assessment of Cancer Therapy Endocrine Subscale (FACT-ES) comprising 18 items (each has score range from 0 to 4) with a possible minimum total score of 0 and maximum total score of 72 (72 is best). Functional Assessment of Chronic Illness Therapy (FACIT) guidelines will be used for scoring and interpretation of the FACT-ES total score.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Female gender
  • Premenopausal status measured within 14 days Prior to randomization: Estradiol (E2) must be above 54 pg/mL (or above 198 pmol/L
  • Age ≥ 18 years
  • Performance Status - Eastern Cooperative Oncology Group (ECOG) 0-1
  • Histologically confirmed invasive breast cancer: Primary tumor greater than 2 cm Diameter, any nodal stage, no evidence of metastasis (M0)
  • Primary tumor must have ER and PgR >50% of the cells
  • Primary tumor must be HER2-negative (by IHC and/or ISH)
  • 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), 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.
  • The patient must be willing to use effective non-hormonal contraception after the pregnancy test and up to surgery. Oral, injectable, or implant hormonal contraceptives or medicated IUD are not allowed within 2 months prior to randomization and during the trial.
  • 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 for the determination of the primary endpoint.
  • The patient agrees to make tumor available for submission for central pathology review and for translational studies as part of this protocol

Exclusion Criteria:

  • Postmenopausal
  • Any hormonal treatment (e.g., oral, injectable, implant, or medicated IUD) in the previous 2 months
  • Presence of HER2 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
  • A history of malignant neoplasms within the past 10 years, except for curatively treated,Basal and squamous cell carcinoma of the skin, carcinoma in situ of the cervix, carcinoma in situ of the bladder
  • Previous ipsilateral breast cancer (invasive or in situ) at any time
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02005887


Locations
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Italy
Azienda Ospedaliero-Universitaria Policlinico S. Orsola-Malpighi di Bologna
Bologna, Italy, 40138
Ospedali Galliera
Genova, Italy, 16128
Istituto Europeo di Oncologia, IEO
Milano, Italy, 20141
Salvatore Maugeri Fondation
Pavia, Italy, 27100
Istituto Toscana Tumori
Prato, Italy, 59100
Ospedale degli Infermi
Rimini, Italy, 47037
A.O "Ospedale di Circolo e Fondazione" Macchi
Varese, Italy, 2100
Sponsors and Collaborators
International Breast Cancer Study Group
Investigators
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Study Chair: Silvia Dellapasqua, MD European Institute of Oncology,Milan,Italy
Study Chair: Marco Colleoni, MD European Institute of Oncology, Milan, Italy
  Study Documents (Full-Text)

Documents provided by International Breast Cancer Study Group:
Statistical Analysis Plan  [PDF] October 1, 2017
Study Protocol  [PDF] December 20, 2012


Publications:
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Responsible Party: International Breast Cancer Study Group
ClinicalTrials.gov Identifier: NCT02005887     History of Changes
Other Study ID Numbers: IBCSG 41-13
2012-005326-29 ( EudraCT Number )
First Posted: December 9, 2013    Key Record Dates
Results First Posted: May 29, 2019
Last Update Posted: May 29, 2019
Last Verified: May 2019

Keywords provided by International Breast Cancer Study Group:
Premenopausal patients
ER-positive
PgR+ (>50%)
HER2-negative or not amplified

Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Letrozole
Triptorelin Pamoate
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Luteolytic Agents
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Antineoplastic Agents, Hormonal