Clinical trial NCT00331097: ELDA: Elderly Breast Cancer - Docetaxel in Adjuvant Treatment
Official title: Adjuvant Chemotherapy in Elderly Patients With Breast Cancer: Weekly Docetaxel vs. CMF
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Keywords: elderly
adjuvant therapy
intermediate risk
high risk
Lead sponsor: National Cancer Institute, Naples
Sponsor class: OTHER
First posted: 2006-05-29
Enrollment: 300
Sex: FEMALE
Minimum age (years): 65
Maximum age (years): 80
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare disease free survival of elderly breast cancer patients treated with standard adjuvant chemotherapy (CMF) versus experimental adjuvant chemotherapy (weekly docetaxel).

Detailed description: Adjuvant combination chemotherapy, given after breast cancer surgery, has been established as the standard approach to reduce the risk of breast cancer recurrence in those patients at intermediate or high risk for recurrence. However, since elderly patients have been underrepresented in past clinical trials, the optimal adjuvant therapy for elderly patients at risk for recurrence has not yet been defined.

Docetaxel is one of the most active drugs for patients with metastatic breast cancer and several trials are evaluating its efficacy in the adjuvant setting. Administration of docetaxel on a weekly schedule is effective and well tolerated in women with metastatic breast cancer.

In this study, patients from ages 65 to 80 will be randomized to one of two treatment strategies:

* standard adjuvant chemotherapy with CMF (cyclophosphamide, methotrexate, and 5-fluorouracil given intravenously on days 1 and 8 of each cycle)
* experimental adjuvant chemotherapy with weekly docetaxel (given intravenously on days 1,8, and 15 of each cycle)

In both treatment strategies:

* 4 cycles of chemotherapy will administered for patients at least 10% positive for ER or PgR, and 6 cycles will administered for patients expressing \< 10% ER or PgR
* patients with any positive expression of ER or PgR will receive adjuvant hormonal therapy with tamoxifen (20mg/day for 5 years) after concluding chemotherapy
* adjuvant radiation therapy will be given to patients who are candidates at the conclusion of chemotherapy and within 6 months of surgery.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed invasive unilateral breast cancer
* Age \> 65 and \< 80 years
* Intermediate-high risk of recurrence according to St. Gallen criteria: ER negative and PgR negative, or axillary lymph node metastasis, or tumor size \> 2 cm, or tumor grade 2 or 3 (intermediate or high)

Exclusion Criteria:

* Performance status \>1
* Distant metastasis
* Concomitant malignancy or malignancy within previous 5 years (except basal cell or spinocellular skin cancer and in situ cervical cancer if they have been adequately treated
* Previous breast cancer treatment
* Neutrophils \< 2000/mm3 or platelets \< 100000/mm3 or haemoglobin \< 10 g/dl
* Creatinine \> 1.25 the upper normal limit
* GOT and-or GPT and/or bilirubin \> 1.25 the upper normal limit
* Concomitant conditions that contraindicate the use of the drugs in the protocol
* Incapacity or refusal to provide informed consent

Primary outcomes:
measure: disease free survival
timeFrame: at 5 years
Secondary outcomes:
measure: toxicity
timeFrame: weekly
measure: compliance
timeFrame: every 3 weeks
measure: quality of life
timeFrame: baseline and every 3 weeks during therapy
measure: overall survival
timeFrame: at 5 years
Other outcomes:
Locations:
city: Monteforte Irpino
country: Italy
facility: Azienda Sanitaria S. Giuseppe Moscati
state: AV
city: Benevento
country: Italy
facility: Azienda Ospedaliera G. Rummo
state: BN
city: Sant'Andrea delle Frate
country: Italy
facility: Policlinico Monteluce
state: PG
city: Napoli
country: Italy
facility: Azienda Ospedaliera Cardarelli
city: Napoli
country: Italy
facility: Istituto Nazionale dei Tumori, Divisione di Oncologia Medica C
city: Napoli
country: Italy
facility: Università Federico II, Cattedra di Oncologia Medica
city: Treviglio
country: Italy
facility: Az. Osp. Treviglio - Caravaggio
city: Vallo della Lucania
country: Italy
facility: Ospedale S. Luca ASL SA 3
Study officials:
affiliation: NCI Naples, Division of Medical Oncology C
name: Andrea De Matteis, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: NCI Naples, Division of Surgical Oncology A
name: Giuseppe D'Aiuto, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: NCI Naples, Clinical Trials Unit
name: Francesco Perrone, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nuzzo F, Morabito A, De Maio E, Di Rella F, Gravina A, Labonia V, Landi G, Pacilio C, Piccirillo MC, Rossi E, D'Aiuto G, Thomas R, Gori S, Colozza M, De Placido S, Lauria R, Signoriello G, Gallo C, Perrone F, de Matteis A. Weekly docetaxel versus CMF as adjuvant chemotherapy for elderly breast cancer patients: safety data from the multicentre phase 3 randomised ELDA trial. Crit Rev Oncol Hematol. 2008 May;66(2):171-80. doi: 10.1016/j.critrevonc.2007.10.006. Epub 2007 Dec 21.
citation: Perrone F, Nuzzo F, Di Rella F, Gravina A, Iodice G, Labonia V, Landi G, Pacilio C, Rossi E, De Laurentiis M, D'Aiuto M, Botti G, Forestieri V, Lauria R, De Placido S, Tinessa V, Daniele B, Gori S, Colantuoni G, Barni S, Riccardi F, De Maio E, Montanino A, Morabito A, Daniele G, Di Maio M, Piccirillo MC, Signoriello S, Gallo C, de Matteis A. Weekly docetaxel versus CMF as adjuvant chemotherapy for older women with early breast cancer: final results of the randomized phase III ELDA trial. Ann Oncol. 2015 Apr;26(4):675-682. doi: 10.1093/annonc/mdu564. Epub 2014 Dec 8.
citation: Di Maio M, Gallo C, Leighl NB, Piccirillo MC, Daniele G, Nuzzo F, Gridelli C, Gebbia V, Ciardiello F, De Placido S, Ceribelli A, Favaretto AG, de Matteis A, Feld R, Butts C, Bryce J, Signoriello S, Morabito A, Rocco G, Perrone F. Symptomatic toxicities experienced during anticancer treatment: agreement between patient and physician reporting in three randomized trials. J Clin Oncol. 2015 Mar 10;33(8):910-5. doi: 10.1200/JCO.2014.57.9334. Epub 2015 Jan 26.