The Synergism Or Long Duration (SOLD) Study (SOLD)

A Randomized Phase III Study Comparing Trastuzumab Plus Docetaxel (HT) Followed by 5-FU, Epirubicin, and Cyclophosphamide (FEC) to the Same Regimen Followed by Single-agent Trastuzumab as Adjuvant Treatments for Early Breast Cancer

The purpose of the study is to compare disease-free survival (DFS) of women treated with concomitant trastuzumab plus docetaxel followed by FEC to that of the women treated with the same regimen followed by single-agent trastuzumab to complete one year of trastuzumab administration as adjuvant treatments of early HER2-positive breast cancer.

Study Overview

• Status: Completed
• Conditions: Breast Neoplasms
• Intervention / Treatment: Drug: trastuzumab (9 weeks) + docetaxel; Drug: trastuzumab (9 weeks) + docetaxel + CEF + trastuzumab (up to 51 weeks)

• Study Type: Interventional
• Enrollment (Actual): 2168
• Phase: Phase 3

Contacts and Locations

Study Locations

• Finland
  • Helsinki, Finland, 00029 HUS
    • Helsinki University Central Hospital, Department of Oncology

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patient has provided a written informed consent prior to study-specific screening procedures, with the understanding that she has the right to withdraw from the study at any time, without prejudice.
2. Woman > 18 years of age.
3. Histologically confirmed invasive breast cancer.
4. HER2-positive breast cancer (preferably assessed with CISH or FISH; if not available with immunohistochemistry 3+)

5. A high risk of breast cancer recurrence with one of the following:

   • Pathological N0 with the longest invasive tumor diameter >5 mm
   • Histologically confirmed regional node positive disease (pN+; nodal isolated tumor cells/cell clusters < 0.2 mm in diameter (ITP) are not counted as a metastasis)

Exclusion Criteria:

1. Presence of distant metastases.
2. Inflammatory breast cancer.
3. pT1bN0M0 (i.e. the longest tumor diameter 6 to 10 mm, node-negative) and histological grade 1.
4. Clinically significant (i.e. active) cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmia not well controlled with medication) or myocardial infarction within the last 12 months.
5. Left ventricular ejection fraction less than 50% (or under the institutional normal reference range) assessed by echocardiography or isotope cardiography.
6. ER, PgR and HER-2 status (via in situ hybridization or immunohistochemistry) not determined.
7. Primary systemic cancer therapy (neoadjuvant chemotherapy or endocrine therapy) has been administered prior to breast surgery.
8. The WHO performance status > 1.
9. Pregnant or lactating women.
10. Women of childbearing potential unless using a reliable and appropriate contraceptive method. Women must have been amenorrheic for at least 12 months prior to study entry to be considered postmenopausal and to have no childbearing potential. Women of childbearing potential (menstruating within 12 months of study entry), or with no hysterectomy and age < 55, must have a negative pregnancy test at baseline.
11. More than 12 weeks between breast surgery and date of randomization.
12. Organ allografts with immunosuppressive therapy required.
13. Major surgery (except breast surgery) within 4 weeks prior to study treatment start, or lack of complete recovery from the effects of major surgery.
14. Participation in any investigational drug study within 4 weeks preceding treatment start.
15. Patients with a history of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant precluding study participation.
16. History of another malignancy within the last five years except cured basal cell carcinoma of skin or carcinoma in situ of the uterine cervix.

17. One or more of the following:

    • Blood hemoglobin < 10.0 g/dL, neutrophils < 1.5 x 109/L, platelet count < 120 x 109/L
    • Serum/plasma creatinine > 1.5 x Upper Limit of Normal (ULN)
    • Serum/plasma bilirubin > ULN
    • Serum/plasma ALT and/or AST > 1.5 x ULN
    • Serum/plasma alkaline phosphatase > 2.5 x ULN
18. Serious uncontrolled infection or other serious uncontrolled concomitant disease.
19. Unwilling or unable to comply with the protocol for the duration of the study.
20. History of hypersensitivity to the investigational products or to drugs with similar chemical structures.
21. Pre-existing motor or sensory neurotoxicity of a severity ≥ grade 2 by CTCAE version 3, unless related to mechanical etiology.

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
Active Comparator: A; Weekly or 3-weekly trastuzumab plus 3-weekly docetaxel (3 cycles) (HT) -> 3-weekly FE75C (3 cycles) (HT x3 -> FE75C x3)	Drug: trastuzumab (9 weeks) + docetaxel; Patients diagnosed with early breast cancer with a high risk of disease recurrence will be randomly allocated to one of the following 2 arms in a 1:1 ratio: A. Weekly or 3-weekly trastuzumab plus 3-weekly docetaxel (3 cycles) (HT) -> 3-weekly FE75C (3 cycles) (HT x3 ->FE75C x3) B. Weekly or 3-weekly trastuzumab plus 3-weekly docetaxel (3 cycles) (HT) -> 3-weekly FE75C (3 cycles) -> trastuzumab to complete 1 year (14 3-weekly infusions) (HT x3 ->FE75C x3 -> H3wkly x14)
Active Comparator: B; Weekly or 3-weekly trastuzumab plus 3-weekly docetaxel (3 cycles) (HT) -> 3-weekly FE75C (3 cycles) -> trastuzumab to complete 1 year (14 3-weekly infusions) (HT x3 ->FE75C x3 -> H3wkly x14)	Drug: trastuzumab (9 weeks) + docetaxel + CEF + trastuzumab (up to 51 weeks); Weekly or 3-weekly trastuzumab plus 3-weekly docetaxel (3 cycles) (HT) -> 3-weekly FE75C (3 cycles) -> trastuzumab to complete 1 year (14 3-weekly infusions) (HT x3 ->FE75C x3 -> H3wkly x14)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Disease-free survival (DFS)	3-10years

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival, distant disease-free survival, cardiac event-free disease-free survival, left ventricle ejection fractions, adverse events, quality of life	3-10years

Collaborators and Investigators

• Sponsor: Finnish Breast Cancer Group

Publications and helpful links

General Publications

• Joensuu H, Fraser J, Wildiers H, Huovinen R, Auvinen P, Utriainen M, Nyandoto P, Villman KK, Halonen P, Granstam-Bjorneklett H, Lundgren L, Sailas L, Turpeenniemi-Hujanen T, Tanner M, Yachnin J, Ritchie D, Johansson O, Huttunen T, Neven P, Canney P, Harvey VJ, Kellokumpu-Lehtinen PL, Lindman H. Effect of Adjuvant Trastuzumab for a Duration of 9 Weeks vs 1 Year With Concomitant Chemotherapy for Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: The SOLD Randomized Clinical Trial. JAMA Oncol. 2018 Sep 1;4(9):1199-1206. doi: 10.1001/jamaoncol.2018.1380.

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: January 3, 2008
• First Submitted That Met QC Criteria: January 14, 2008
• First Posted (Estimate): January 15, 2008

Study Record Updates

• Last Update Posted (Estimate): March 6, 2015
• Last Update Submitted That Met QC Criteria: March 5, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: breast cancer; adjuvant therapy; chemotherapy; trastuzumab
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Immunological; Docetaxel; Trastuzumab
• Other Study ID Numbers: Protocol number FBCSG-01-2007; EudraCT number 2007-002016-26