Clinical trial NCT00311636: Triptorelin in Preventing Early Menopause in Premenopausal Women Who Are Receiving Chemotherapy for Stage I, Stage II, or Stage III Breast Cancer That Has Been Removed By Surgery
Official title: Prevention of Chemotherapy-induced Menopause by Temporary Ovarian Suppression With Triptorelin Vs. Control in Young Breast Cancer Patients. A Randomized Phase III Multicenter Study [PROMISE]
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Keywords: stage I breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2006-04-06
Enrollment: 280
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: SUPPORTIVE_CARE

Brief summary: RATIONALE: Chemotherapy may cause early menopause in premenopausal women. Triptorelin may prevent this from happening.

PURPOSE: This randomized phase III trial is studying triptorelin to see how well it works in preventing early menopause in premenopausal women who are receiving chemotherapy for stage I, stage II, or stage III breast cancer that has been removed by surgery.

Detailed description: OBJECTIVES:

Primary

* Evaluate the incidence of chemotherapy-induced early menopause in premenopausal women undergoing adjuvant chemotherapy in combination with vs without triptorelin for previously resected stage I-III breast cancer.

Secondary

* Compare the toxicity of adjuvant chemotherapy and triptorelin vs adjuvant chemotherapy alone.

OUTLINE: This is a prospective, open-label, multicenter, randomized study. Patients are randomized to 1 of 2 treatment arms.

* Arm I (adjuvant chemotherapy alone): Patients receive adjuvant chemotherapy alone.
* Arm II (adjuvant chemotherapy and triptorelin): Patients receive adjuvant chemotherapy and triptorelin intramuscularly 1 week before and then every 4 weeks for the duration of chemotherapy. The last dose of triptorelin is given before the last course of chemotherapy.

Patients with hormone-sensitive tumors who resume ovarian function after stopping chemotherapy and triptorelin restart triptorelin until ovarian function is suppressed for 2 years.

Patients undergo menopausal status assessment, using follicle-stimulating hormone, luteinizing hormone, and estradiol as biochemical markers, at baseline and 3, 6, 9, and 12 months after the last course of chemotherapy.

After completion of study treatment, patients are followed at 3, 6, 9, and 12 months.

PROJECTED ACCRUAL: A total of 280 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed breast cancer resected at time of original diagnosis

  * Stage I-III disease
* Candidate for 1 of the following adjuvant chemotherapy regimens:

  * FEC (fluorouracil, epirubicin hydrochloride, and cyclophosphamide) every 21 or 28 days
  * CMF (cyclophosphamide, methotrexate, and fluorouracil) every 28 days
  * A→CMF (doxorubicin hydrochloride followed by CMF)
  * EC→P (epirubicin hydrochloride and cyclophosphamide every 21 days followed by paclitaxel every 21 days)
  * FEC→P (FEC every 21 days followed by paclitaxel every 21 days)
  * EC→D (EC every 21 days followed by docetaxel every 21 days)
  * AC (doxorubicin hydrochloride and cyclophosphamide) every 21 days
  * AC→P (AC every 21 days followed by paclitaxel every 21 days)
  * E→CMF (epirubicin hydrochloride followed by CMF every 28 days)
* No evidence of metastases or localized or distant recurrence

  * Investigation to exclude metastases required for any suspicious manifestation
* Premenopausal, defined as the presence of active menstrual cycles or normal menses within six weeks before initiation of chemotherapy
* Hormone receptor status not specified

PATIENT CHARACTERISTICS:

* Female
* No other malignancy within the past 5 years except basal cell or squamous cell skin cancer or adequately treated in situ carcinoma of the cervix
* No history of noncompliance to medical regimens or patients who are considered potentially unreliable
* Not pregnant or nursing
* Negative pregnancy test

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* No prior chemotherapy and/or radiotherapy for cancer or non-neoplastic disease
* No other concurrent hormonal therapy except for tamoxifen

Primary outcomes:
measure: Chemotherapy-induced early menopause as measured by follicle-stimulating hormone, 17 beta estradiol levels, and menstrual activity resumption at 1 year following the completion of chemotherapy
Secondary outcomes:
measure: Toxicity as measured by Common Toxicity Criteria at each chemotherapy course
Other outcomes:
Locations:
city: Castelfranco - TV
country: Italy
facility: Ospedale Civile
city: Como
country: Italy
facility: Ospedale Sant Anna
city: Cuneo
country: Italy
facility: Ospedale Santa Croce
city: Florence
country: Italy
facility: Azienda Ospedaliera di Firenze
city: Genoa
country: Italy
facility: Istituto Nazionale per la Ricerca sul Cancro
city: Livorno
country: Italy
facility: Presidio Ospedaliero di Livorno
city: Mantova
country: Italy
facility: Carlo Poma Hospital
city: Naples
country: Italy
facility: Federico II University Medical School
city: Naples
country: Italy
facility: Seconda Universita di Napoli
city: Naples
country: Italy
facility: Istituto G. Pascale
city: Perugia
country: Italy
facility: Ospedale Silvestrini
city: Pisa
country: Italy
facility: Ospedale Santa Chiara Pisa
city: Rome
country: Italy
facility: Istituto Regina Elena
city: Sassari
country: Italy
facility: Ospedale Civile ASL 1
city: Sora
country: Italy
facility: Ospedale SS Trinita
city: Treviglio
country: Italy
facility: Ospedale Treviglio Caravaggio
city: Trieste
country: Italy
facility: Ospedale Maggiore dell' Universita
city: Turin
country: Italy
facility: Universita di Torino
Study officials:
affiliation: IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
name: Lucia Del Mastro, MD
role: STUDY_CHAIR
References:
citation: Del Mastro L, Boni L, Michelotti A, Gamucci T, Olmeo N, Gori S, Giordano M, Garrone O, Pronzato P, Bighin C, Levaggi A, Giraudi S, Cresti N, Magnolfi E, Scotto T, Vecchio C, Venturini M. Effect of the gonadotropin-releasing hormone analogue triptorelin on the occurrence of chemotherapy-induced early menopause in premenopausal women with breast cancer: a randomized trial. JAMA. 2011 Jul 20;306(3):269-76. doi: 10.1001/jama.2011.991.
citation: Lambertini M, Boni L, Michelotti A, Gamucci T, Scotto T, Gori S, Giordano M, Garrone O, Levaggi A, Poggio F, Giraudi S, Bighin C, Vecchio C, Sertoli MR, Pronzato P, Del Mastro L; GIM Study Group. Ovarian Suppression With Triptorelin During Adjuvant Breast Cancer Chemotherapy and Long-term Ovarian Function, Pregnancies, and Disease-Free Survival: A Randomized Clinical Trial. JAMA. 2015 Dec 22-29;314(24):2632-40. doi: 10.1001/jama.2015.17291.