TRial on the Endocrine Activity of Neoadjuvant Degarelix

NCT02005887 | Completed Phase 2 Results DMC

• 2 other identifiers: IBCSG 41-132012-005326-29
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 7

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.

Conditions

Breast Cancer Invasive Nos

Keywords

Premenopausal patients; ER-positive; PgR+ (>50%); HER2-negative or not amplified

Outcome Measures

Primary Outcomes (1)

• Time to Optimal Ovarian Function Suppression

  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.

  up to 24 weeks

Secondary Outcomes (6)

• Ki67 Proliferation Marker Changes

  Before day1 of cycle 1 and surgery

• Preoperative Endocrine Prognostic Index (PEPI) Score

  After 24 weeks or the time of surgery

• Best Overall (Disease) Response

  From day 1 of cycle 1 across all time points until disease progression

• Percentage of Patients With Node-negative Disease at Surgery

  During surgery, an average of 2 hours

• Percentage of Patients Who Underwent Breast-Conserving Surgery (BCS)

  During surgery, an average of 2 hours

Study Arms (2)

triptorelin + letrozole

EXPERIMENTAL

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; Drug: letrozole

degarelix + letrozole

EXPERIMENTAL

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; Drug: letrozole

Interventions

triptorelin DRUG

Triptorelin 3.75 mg injected into the muscle on day 1 every 28 days for 6 cycles (1 cycle= 28 days)

Also known as: decapeptyl

triptorelin + letrozole

degarelix DRUG

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)

Also known as: firmagon

degarelix + letrozole

letrozole DRUG

Letrozole 2.5 mg orally every day for 6 cycles

Also known as: femara

degarelix + letrozole; triptorelin + letrozole

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• ETOP IBCSG Partners Foundation: lead

Study Sites (7)

Azienda Ospedaliero-Universitaria Policlinico S. Orsola-Malpighi di Bologna

Bologna, 40138, Italy

Location

Ospedali Galliera

Genova, 16128, Italy

Location

Istituto Europeo di Oncologia, IEO

Milan, 20141, Italy

Location

Salvatore Maugeri Fondation

Pavia, 27100, Italy

Location

Istituto Toscana Tumori

Prato, 59100, Italy

Location

Ospedale degli Infermi

Rimini, 47037, Italy

Location

A.O "Ospedale di Circolo e Fondazione" Macchi

Varese, 2100, Italy

Location

Related Publications (5)

• Kaufmann M, von Minckwitz G, Mamounas EP, Cameron D, Carey LA, Cristofanilli M, Denkert C, Eiermann W, Gnant M, Harris JR, Karn T, Liedtke C, Mauri D, Rouzier R, Ruckhaeberle E, Semiglazov V, Symmans WF, Tutt A, Pusztai L. Recommendations from an international consensus conference on the current status and future of neoadjuvant systemic therapy in primary breast cancer. Ann Surg Oncol. 2012 May;19(5):1508-16. doi: 10.1245/s10434-011-2108-2. Epub 2011 Dec 23.

  PMID: 22193884 BACKGROUND

• Fisher B, Bryant J, Wolmark N, Mamounas E, Brown A, Fisher ER, Wickerham DL, Begovic M, DeCillis A, Robidoux A, Margolese RG, Cruz AB Jr, Hoehn JL, Lees AW, Dimitrov NV, Bear HD. Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol. 1998 Aug;16(8):2672-85. doi: 10.1200/JCO.1998.16.8.2672.

  PMID: 9704717 BACKGROUND

• Guarneri V, Broglio K, Kau SW, Cristofanilli M, Buzdar AU, Valero V, Buchholz T, Meric F, Middleton L, Hortobagyi GN, Gonzalez-Angulo AM. Prognostic value of pathologic complete response after primary chemotherapy in relation to hormone receptor status and other factors. J Clin Oncol. 2006 Mar 1;24(7):1037-44. doi: 10.1200/JCO.2005.02.6914.

  PMID: 16505422 BACKGROUND

• Kuerer HM, Newman LA, Smith TL, Ames FC, Hunt KK, Dhingra K, Theriault RL, Singh G, Binkley SM, Sneige N, Buchholz TA, Ross MI, McNeese MD, Buzdar AU, Hortobagyi GN, Singletary SE. Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy. J Clin Oncol. 1999 Feb;17(2):460-9. doi: 10.1200/JCO.1999.17.2.460.

  PMID: 10080586 BACKGROUND

• Dellapasqua S, Gray KP, Munzone E, Rubino D, Gianni L, Johansson H, Viale G, Ribi K, Bernhard J, Kammler R, Maibach R, Rabaglio-Poretti M, Ruepp B, Di Leo A, Coates AS, Gelber RD, Regan MM, Goldhirsch A, Colleoni M; International Breast Cancer Study Group. Neoadjuvant Degarelix Versus Triptorelin in Premenopausal Patients Who Receive Letrozole for Locally Advanced Endocrine-Responsive Breast Cancer: A Randomized Phase II Trial. J Clin Oncol. 2019 Feb 10;37(5):386-395. doi: 10.1200/JCO.18.00296. Epub 2018 Dec 27.

  PMID: 30589600 DERIVED

MeSH Terms

Interventions

Triptorelin Pamoate; acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide; Letrozole

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Meredith M. Regan
• Organization: International Breast Cancer Study Group

mregan@jimmy.harvard.edu

+1 617-632-3012

Study Officials

• Silvia Dellapasqua, MD

  European Institute of Oncology,Milan,Italy

  STUDY CHAIR

• Marco Colleoni, MD

  European Institute of Oncology, Milan, Italy

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2013
• First Posted: December 9, 2013
• Study Start: February 1, 2014
• Primary Completion: August 25, 2017
• Study Completion: August 25, 2017
• Last Updated: May 29, 2019
• Results First Posted: May 29, 2019

Record last verified: 2019-05

Locations

IT (7)