Secondary Adjuvant Long Term Study With Arimidex (SALSA)

A Prospective, Randomized, Open, Multicentre Phase III-study to Assess the Efficacy of Secondary Adjuvant Endocrine Anastrozole Therapy for 2 Further Yrs vs 5 Further Yrs in Patients With HR +ve Breast Cancer After 5-yr Primary Adjuvant Endocrine Therapy

The study assesses the effect of further 2 years vs further 5 years of adjuvant treatment with anastrozole after initial 5 years of adjuvant endocrine therapy.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Anastrozole

Detailed Description

ABCSG 16 S.A.L.S.A is assessing the effect of further 2 years vs further 5 years of adjuvant treatment with anastrozole after initial 5 years of adjuvant endocrine therapy. S.A.L.S.A. is a randomized open multicentered phase III study comparing the efficacy of secondary adjuvant endokrine treatment of Arimidex® (Anastrozol) for 2 or 5 years after primary adjuvant endokrine therapy in patients with hormonreceptor positive mammakarzinom. Patients are examined at screening, after 6 months, then every year until 5 years. The subsequent yearly follow up with mammographie and clinical examination ends 10 years after the screening. S.A.L.S.A. started in February 2004 and has recruited 3484 patients until June 2010 at 78 sites all over Austria.

Primary Endpoint:

1. Proof of the effect of 2 years versus 5 years of Anastrozol after 5 years of adjuvant endocrine therapy on the disease free survival

Secondary endpoint:

1. Proof of the effect of 2 years versus 5 years of Anastrozol after 5 years of adjuvant endocrine therapy on the overall survival
2. Comparison of fracture rate in both therapy groups

3. Comparison of incidence of

   1. a secondary carcinoma except the contralateral mammacarcinoma
   2. contralateral mammacarcinoma in both therapie groups

• Study Type: Interventional
• Enrollment (Actual): 3484
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Amstetten, Austria, 3300
    • Research Site
  • Bad Ischl, Austria, 4820
    • Research Site
  • Baden, Austria, 2500
    • Research Site
  • Bregenz, Austria, 6900
    • Research Site
  • Dornbirn, Austria, 6853
    • Research Site
  • Eisenstadt, Austria, 7000
    • Research Site
  • Feldbach, Austria, 8330
    • Research Site
  • Feldkirch, Austria, 6807
    • Research Site
  • Freistadt, Austria, 4240
    • Research Site
  • Fuerstenfeld, Austria, 8280
    • Research Site
  • Gmunden, Austria, 4810
    • Research Site
  • Graz, Austria, 8036
    • Research Site
  • Guessing, Austria, 7540
    • Research Site
  • Hainburg, Austria, 2410
    • Research Site
  • Hall in Tirol, Austria, 6060
    • Research Site
  • Innsbruck, Austria, 6020
    • Research Site
  • Kirchdorf, Austria, 4560
    • Research Site
  • Klagenfurt, Austria, 9020
    • Research Site
  • Klagenfurt, Austria, 9026
    • Research Site
  • Klagenfurt, Austria, 8020
    • Research Site
  • Krems, Austria, 3500
    • Research Site
  • Kufstein, Austria, 6330
    • Research Site
  • Leoben, Austria, 8700
    • Research Site
  • Lienz, Austria, 9900
    • Research Site
  • Linz, Austria, 4010
    • Research Site
  • Linz, Austria, 4021
    • Research Site
  • Mistelbach, Austria, 2130
    • Research Site
  • Moedling, Austria, 2340
    • Research Site
  • Neunkirchen, Austria, 2620
    • Research Site
  • Oberpullendorf, Austria, 7350
    • Research Site
  • Oberwart, Austria, 7400
    • Research Site
  • Ried im Innkreis, Austria, 4910
    • Research Site
  • Rottenmann, Austria, 8786
    • Research Site
  • Salzburg, Austria, 5020
    • Research Site
  • Scheibbs, Austria, 3270
    • Research Site
  • Schladming, Austria, 8970
    • Research Site
  • Schwarzach, Austria, 5620
    • Research Site
  • St. Poelten, Austria, 3100
    • Research Site
  • St. Veit an der Glan, Austria, 9300
    • Research Site
  • Steyr, Austria, 4400
    • Research Site
  • Vienna, Austria, 1090
    • Research Site
  • Vienna, Austria, 1050
    • Research Site
  • Vienna, Austria, 1070
    • Research Site
  • Vienna, Austria, 1130
    • Research Site
  • Vienna, Austria, 1210
    • Research Site
  • Vienna, Austria, A-1090
    • Research Site
  • Villach, Austria, 9500
    • Research Site
  • Villach, Austria, 9504
    • Research Site
  • Voecklabruck, Austria, 4840
    • Research Site
  • Waidhofen an der Thaya, Austria, 3830
    • Research Site
  • Weiz, Austria, 8160
    • Research Site
  • Wels, Austria, 4600
    • Research Site
  • Wien, Austria, 1130
    • Research Site
  • Wien, Austria, 1090
    • Research Site
  • Wien, Austria, 1220
    • Research Site
  • Wien, Austria, 1140
    • Research Site
  • Wien, Austria, 1021
    • Research Site
  • Wien, Austria, 1160
    • Research Site
  • Wien, Austria, 1180
    • Research Site
  • Wiener Neustadt, Austria, 2700
    • Research Site
  • Wolfsberg, Austria, 9400
    • Research Site
  • Zams, Austria, 6511
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion criteria:

1. Postmenopausal patients with histologically confirmed, local radically treated invasive or minimal-invasiv Mammacarcinom with or without previous chemotherapie and/or radiotherapie.
2. No distant metastasis at randomization
3. No relapse at randomization
4. TNM- classification at time of diagnosis: T1-3, N0 and N+, M0
5. Estrogen- and or progesterone positive before the beginningof primary endocrine therapy
6. Endocrine therapy for 5 years (maximum deviation ±12 months)
7. Therapy break (from the preliminary therapie) maximum 12 months.
8. Informed Consent before the randomisation

Exclusion criteria:

1. Premenopausal patients or patients with non definable menopausal statusat time of randomisation
2. Apparent secondary malignant tumor or status after secondary malignant tumor (Exceptions: simultaniously appearing bilateral breast carcinoma, estrogen- and or progesteronereceptor positive on both sides at the time of diagnosis; in situ carcinomaof the cervix and basal cell carcinoma of the skin)
3. General contraindication respectively hypersensitivity to Anastrozol.
4. In-situ carcinoma of any size with or without Mb. Paget of the Mamilla respectively T4 tumor at the time of first diagnosis.
5. Receptor unknown or negative at time of diagnosis respectively at beginning of primary endocrine therapy
6. Known liver- and/or kidneyinsufficiency
7. Performance Index >2 according to WHO
8. Regular intake of hormon supplement as well as Hormone Replacement Therapy (HRT) more than 6 months since primary surgery of the mamma carcinoma
9. Serious accessory disease, that prevents the adjuvant therapy according to protocol and/or the regular follow-up care.
10. Lacking compliance of the patient
11. Legal incompetence and/or other circumstances, that prevent the patient from understanding the nature, meaning and consequences of the clinical trial
12. Existing psychiatrical diseaseaccording to ICD (especially alcohol addiction) et the time of admission into the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: Anastrozol; 1 mg per day for 2 years	Drug: Anastrozole; 1mg tablet daily; Other Names: Arimidex
Experimental: Arm B: Anastrozol; 1 mg per day for 5 years	Drug: Anastrozole; 1mg tablet daily; Other Names: Arimidex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free Survival After Prolonged Endocrine Treatment	To determine whether 5 years of additional Anastrozole was more effective than 2 years of additional Anastrozole after 5 years of adjuvant endocrine therapy in terms of disease-free survival.	DFS was defined as the time from two years after randomization to the earliest occurrence of loco-regional recurrence, distant recurrence, contralateral new breast cancer, second cancer or death from any cause, assessed up to a maximum of 8.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival After Prolonged Endocrine Treatment	To determine whether 5 years of additional Anastrozole was more effective than 2 years of additional Anastrozole after 5 years of adjuvant endocrine therapy in terms of overall survival.	Overall survival was defined as the time from two years after randomization to death due to any cause, assessed up to a maximum of 8.5 years
Time to First Clinical Fracture	To determine the effect of 2 years versus 5 years of additional Anastrozole after 5 years of adjuvant endocrine therapy on the time to first clinical fracture. Patients without clinical fractures where censored at their last therapy visit (approximately 5 years after randomization).	Time to first clinical fracture was defined as time to first clinical fracture, in the period from 2 years until 5 years after randomization for each patient.
Time to Secondary Carcinoma	To determine whether 5 years of additional Anastrozole was more effective than 2 years of additional Anastrozole after 5 years of adjuvant endocrine therapy in terms of lowering the risk of secondary carcinoma. Subjects without secondary cancer event were censored at the last date when they were known to be secondary cancer free.	Risk of secondary carcinoma was defined as the time from two years after randomization to first occurrence of new secondary cancer without new breast cancer (local or contralateral), assessed up to a maximum of 8.5 years
Time to Contralateral Breast Cancer	To determine whether 5 years of additional Anastrozole was more effective than 2 years of additional Anastrozole after 5 years of adjuvant endocrine therapy in terms of lowering the risk of contralateral breast cancer. Subjects without contralateral breast cancer event were censored at the last date when they were known to be contralateral breast cancer free.	Risk of contralateral breast cancer was defined as the time from two years after randomization to first occurrence of new contralateral breast cancer, assessed up to a maximum of 8.5 years

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: AstraZeneca Austria Medical Director, MD, AstraZeneca

Publications and helpful links

General Publications

• Gnant M, Fitzal F, Rinnerthaler G, Steger GG, Greil-Ressler S, Balic M, Heck D, Jakesz R, Thaler J, Egle D, Manfreda D, Bjelic-Radisic V, Wieder U, Singer CF, Melbinger-Zeinitzer E, Haslbauer F, Sevelda P, Trapl H, Wette V, Wimmer K, Gampenrieder SP, Bartsch R, Kacerovsky-Strobl S, Suppan C, Brunner C, Deutschmann C, Soelkner L, Fesl C, Greil R; Austrian Breast and Colorectal Cancer Study Group. Duration of Adjuvant Aromatase-Inhibitor Therapy in Postmenopausal Breast Cancer. N Engl J Med. 2021 Jul 29;385(5):395-405. doi: 10.1056/NEJMoa2104162.

Helpful Links

• 1033AU/0003 CSP redacted
• 1033AU/0003 SAP redacted

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2004
• Primary Completion (Actual): June 30, 2017
• Study Completion (Actual): June 30, 2017

Study Registration Dates

• First Submitted: February 23, 2006
• First Submitted That Met QC Criteria: February 23, 2006
• First Posted (Estimate): February 24, 2006

Study Record Updates

• Last Update Posted (Actual): October 2, 2019
• Last Update Submitted That Met QC Criteria: October 1, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Hormone receptor positive breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Anastrozole
• Other Study ID Numbers: 1033AU/0003; ABCSG 16; D5392L00016; SALSA