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Breast CancerOPTIMALNCT02335957

OPTimizing Irradiation Through Molecular Assessment of Lymph Node (OPTIMAL)

A study testing Irradiation in people with Breast Cancer, run by Grupo de Investigación Clínica en Oncología Radioterapia at 50 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The main purpose of this study is to show the non-inferiority of the incidental irradiation, as compared to intentional irradiation of the axillary nodes, in terms of 5-years disease-free survival (DFS) of early stage breast cancer patients with limited affectation of sentinel node assessed by OSNA (250 to 15,000… Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer
What is being tested?
Irradiation
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
489 participants
Where
50 sitesin 3 countries
Study dates
Apr 2015to Jul 2021
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Infiltrating, ductal carcinoma of the breast.
  • Treated with conservative surgery (tumorectomy or quadrantectomy) without lymphadenectomy.
  • Sentinel lymph node assessed by OSNA, with TTL in the range 250 - 15,000 copies/μL.
  • Age ≥ 18 yrs old.
  • Karnofsky Index ≥ 70 %.
  • Signed Informed Consent.

Who cannot join

  • Other types of breast cancer different from infiltrating ductal carcinoma.
  • Bilateral breast cancer.
  • Males.
  • Mastectomy or axillary homolateral lymph node dissection.
  • Previous thoracic irradiation therapy.
  • Systemic neoadjuvant therapy previous to surgery.
Show all 9Show fewer
  • Contraindications of radiotherapy (pregnancy, severe collagen diseases).
  • Other neoplasms.
  • Severe associated comorbidities that, according to the investigator criteria, may interfere with the study evaluations.

Trial locations and contacts

50 sites in 3 countries.

50 sites in 3 countries

Spain46 sites

  • Centro Onoclógico de Galicia

    A Coruña

  • Complejo Hospitalario Universitario de Albacete

    Albacete

  • Hospital Universitario de la Ribera

    Alzira

  • Hospital Universitario Infanta Cristina

    Badajoz

  • Hospital de Cruces

    Barakaldo, Bilbao

  • Centro Médico Teknon

    Barcelona

  • Clínica Platon

    Barcelona

  • Hospital Clínic de Barcelona

    Barcelona

  • Hospital del Mar

    Barcelona

  • ICO Duran i Reynals

    Barcelona

  • Hospital Universitario de Burgos

    Burgos

  • Hospital Universitario Puerta del Mar

    Cadiz

  • Hospital General Universitario de Santa Lucía

    Cartagena, Murcia

  • Hospital Provincial de Castellón

    Castelló

  • Hospital General Universitario de Ciudad Real

    Ciudad Real

  • Hospital de Donostia

    Donostia / San Sebastian

  • Complejo Hospitalario Universitario de Fuenlabrada

    Fuenlabrada, Madrid

  • Fundación Hospital de Jove

    Gijón, Principality of Asturias

  • Hospital Universitario Virgen de las Nieves

    Granada

  • Hospital Universitario de Gran Canaria Dr. Negrín

    Las Palmas de Gran Canaria, Canary Islands

  • Hospital Universitario de León

    León

  • Hospital Universitari Arnau de Vilanova

    Lleida

  • Hospital Clínico Universitario de San Carlos

    Madrid

  • Hospital Fundación Jiménez Díaz

    Madrid

  • Hospital Ramon y Cajal

    Madrid

  • Hospital Universitario 12 de Octubre

    Madrid

  • Hospital Universitario Gregorio Marañón

    Madrid

  • Hospital Universitario la Paz

    Madrid

  • Hospital Universitario Puerta de Hierro

    Majadahonda, Madrid

  • Hospital General Universitario Virgen de la Arrixaca

    Murcia

  • Complejo Hospitalario de Navarra

    Pamplona, Navarre

  • Hospital Universitari Sant Joan de Reus

    Reus

  • Hospital Universitario de Salamanca

    Salamanca

  • Hospital Clínico Universitario de Santiago

    Santiago de Compostela

  • Hospital Virgen de la Macarena

    Seville

  • Hospital Virgen del Rocío

    Seville

  • Hospital Clinico Universitario de Valencia

    Valencia

  • Hospital General Universitario de Valencia

    Valencia

  • Hospital Universitari i Politecnic la Fe

    Valencia

  • Instituto Valenciano de Oncología (IVO)

    Valencia

  • Hospital Clínico Universitario de Valladolid

    Valladolid

  • Complejo Hospitalario Universitario de Vigo

    Vigo

  • Hospital Universitario de Araba

    Vitoria-Gasteiz

  • Hospital Virgen de la Concha

    Zamora

  • Hospital Clínico Universitario Lozano Blesa

    Zaragoza

  • Hospital Universitario Miguel Servet

    Zaragoza

Other trials in Spain

Portugal3 sites

  • Hospital Espírito Santo

    Evora

  • Centro Hospitalar De São João

    Porto

  • Hospital Distrital de Santarém

    Santarém

Other trials in Portugal

Italy1 site

  • Hospital de Perugia

    Perugia

Other trials in Italy

About this study

The main purpose of this study is to show the non-inferiority of the incidental irradiation, as compared to intentional irradiation of the axillary nodes, in terms of 5-years disease-free survival (DFS) of early stage breast cancer patients with limited affectation of sentinel node assessed by OSNA (250 to 15,000 copies/uL), treated with breast-conservative surgery without axillary lymphadenectomy.

Read the detailed description

Since long, the standard loco-regional treatment of the early-stage breast cancer is breast conservative surgery (tumorectomy) followed by a selective biopsy of the sentinel lymph node and, if positive, lymphadenectomy of axillary levels I and II. Complementary irradiation of the breast and ganglionar areas has shown to reduce disease-specific mortality. Therefore, adjuvant radiotherapy of the whole breast is currently indicated after conservative surgery.

The recommendation to irradiate axillary lymph nodes is clear in patients with more than three affected nodes. The standard volumes to irradiate after lymphadenectomy include supraclavicular and level III axillary regions, while axillary levels I and II, and the internal breast lymph node chain, are reserved for cases of cumbersome axillary affectation, patients who have not undergone lymphadenectomy or it was insufficient, or affectation of the internal breast lymph node chain.

However, when only 1 to 3 nodes are affected, there is no unanimity on the recommendation of radiotherapy, despite some studies have shown that irradiation improves survival. In addition, the National Cancer Institute of Canada trial (NCIC-CTGMA20), high risk patients with negative lymph nodes and patients with positive lymph nodes (most of them with 1 to 3 affected nodes) showed that local irradiation with or without regional lymph node irradiation improved disease-free survival, as well as loco-regional and distant disease control. Moreover, a systematic review including more than 20,000 patients from 45 studies concludes that the irradiation of the breast reduced the loco-regional relapse, even in patients without affected lymph nodes.

One Step Nucleic Acid Amplification (OSNA) is a technique developed by Sysmex Corporation that allows a readily and complete analysis of sentinel lymph nodes during surgery. OSNA provides a quantification of the Cytokeratin 19 (CK19) tumour cell marker in the messenger ribonucleic acid (mRNA) of the sentinel node, the result being expressed as "total tumour load" (TTL), which is a discrete number of copies per microliter. This technique has shown ability to discriminate macrometastasis, micrometastasis or negativity, and to predict affectation of non-sentinel lymph nodes. According to previous results, a TTL < 15,000 is associated with a 85% probability of non-affectation of (non-sentinel) axillar lymph nodes.

The therapeutic value of the axillary lymphadenectomy has been questioned since long, and the recent publication of the Z0011 study proposes solely a selective biopsy of the sentinel lymph node. This has impacted clinical practice guidelines as prestigious as those of the National Comprehensive Cancer Network; however, irradiation is always considered in these cases.

In summary, the amount of nodal volumes to irradiate in early stages of breast cancer is under discussion, particularly in the case of patients not submitted to axillar lymphadenectomy despite affectation of sentinel lymph nodes. In most cases, the irradiation of the breast implies "incidental" irradiation of the axillary level I, and in some cases the level II. For this reason, some groups have decided not to irradiate these axillary regions intentionally, while others advocate irradiating these regions intentionally.

Conditions
Breast Cancer
Being tested
Irradiation
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IrradiationRadiation

    Intentional versus incidental irradiation of lymphatic node areas, administered using a lineal accelerator, after 3D delimitation of the supraclavicular and axillary levels I, II and III. In both treatment arms, further tumoral bed boost will be allowed according to the investigator criteria, whether dose contribution to the nodal areas can be calculated. Due to its nature, interventions cannot be asked.

Study groups in NCT02335957
Study groupRoleWhat they receive
Intentional irradiation of lymph nodesOtherPatients will receive a total dose of 50 Gy in the whole breast and nodal areas(axillary I, II, III, and supraclavicular) with optimization of the technique, in daily fractions of 2 Gy and 5 fractions/week during 5 weeks.
Receives: Radiation: Irradiation
Incidental irradiation of lymph nodesExperimentalPatients will receive a total dose of 50 Gy in the whole breast, but not aimed at nodal areas, with optimization of the technique, in daily fractions of 2 Gy and 5 fractions/week during 5 weeks.
Receives: Radiation: Irradiation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Disease Free Survival

    The primary outcome will be the 5-years DFS. DFS is defined as the time from randomization to any breast cancer-related event, including local, regional or distant recurrence, or death from breast cancer.

    Measured: 5 years

Secondary outcomes (5)

  1. Time to loco-regional recurrence up 5-years

    Loco-regional recurrence during the 5-years follow-up, defined as clinical or image-based detection of tumour in treated breast (local recurrence) or in the ipsilateral axilla or supraclavicular fossa (regional recurrence).

    Measured: 5 years

  2. Time to distant recurrence up 5-years

    Distant recurrence occuring during the 5-years follow-up, defined as defined as clinical or image-based detection of neoplastic affectation of other organs or tissues different from the treated breast, ipsilateral axilla or supraclavicular fossa.

    Measured: 5 years

  3. Number of patients with acute toxicity, defined as any adverse event appearing up to one month after finalization of radiotherapy.

    Acute toxicity, assessed by a selected subset of the Common Terminology Criteria for Adverse Events v4.0 (CTCAE)

    Measured: 7 years

  4. Number of patients with chronic toxicity, defined as any adverse event appearing during follow-up, up to 5 years.

    Chronic toxicity , assessed by a selected subset of the Common Terminology Criteria for Adverse Events v4.0 (CTCAE)

    Measured: 7 years

  5. Total irradiation dose (Gy) received in axillary levels I, II and III, supraclavicular fossa, and internal mammary chain volumes, at the end of radiotherapy.

    Total dose (Gy) received in axillary levels I, II,and II, supraclavicular, and internal mammary chain volumes.

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jan 2015 (estimated)
  2. Study startApr 2015
  3. Primary completionJul 2021
  4. Study completionJul 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
489 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02335957
Sponsor's protocol ID
GIC-RAD-2014-02
Acronym
OPTIMAL
Status last verified
Mar 2022
First submitted
23 Dec 2014
Last updated
1 Apr 2022
Results posted
No
Data monitoring committee
Yes

Publications

  • Kiluk JV, Ly QP, Meade T, Ramos D, Reintgen DS, Dessureault S, Davis M, Shamehdi C, Cox CE. Axillary recurrence rate following negative sentinel node biopsy for invasive breast cancer: long-term follow-up. Ann Surg Oncol. 2011 Dec;18 Suppl 3:S339-42. doi: 10.1245/s10434-009-0704-1. Epub 2009 Sep 24.

    PubMed 19777181

  • Clarke M, Collins R, Darby S, Davies C, Elphinstone P, Evans V, Godwin J, Gray R, Hicks C, James S, MacKinnon E, McGale P, McHugh T, Peto R, Taylor C, Wang Y; Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005 Dec 17;366(9503):2087-106. doi: 10.1016/S0140-6736(05)67887-7.

    PubMed 16360786

  • Early Breast Cancer Trialists' Collaborative Group (EBCTCG); Darby S, McGale P, Correa C, Taylor C, Arriagada R, Clarke M, Cutter D, Davies C, Ewertz M, Godwin J, Gray R, Pierce L, Whelan T, Wang Y, Peto R. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet. 2011 Nov 12;378(9804):1707-16. doi: 10.1016/S0140-6736(11)61629-2. Epub 2011 Oct 19.

    PubMed 22019144

  • Ragaz J, Olivotto IA, Spinelli JJ, Phillips N, Jackson SM, Wilson KS, Knowling MA, Coppin CM, Weir L, Gelmon K, Le N, Durand R, Coldman AJ, Manji M. Locoregional radiation therapy in patients with high-risk breast cancer receiving adjuvant chemotherapy: 20-year results of the British Columbia randomized trial. J Natl Cancer Inst. 2005 Jan 19;97(2):116-26. doi: 10.1093/jnci/djh297.

    PubMed 15657341

  • Overgaard M, Nielsen HM, Overgaard J. Is the benefit of postmastectomy irradiation limited to patients with four or more positive nodes, as recommended in international consensus reports? A subgroup analysis of the DBCG 82 b&c randomized trials. Radiother Oncol. 2007 Mar;82(3):247-53. doi: 10.1016/j.radonc.2007.02.001. Epub 2007 Feb 15.

    PubMed 17306393

  • van Wely BJ, Teerenstra S, Schinagl DA, Aufenacker TJ, de Wilt JH, Strobbe LJ. Systematic review of the effect of external beam radiation therapy to the breast on axillary recurrence after negative sentinel lymph node biopsy. Br J Surg. 2011 Mar;98(3):326-33. doi: 10.1002/bjs.7360. Epub 2010 Nov 30.

    PubMed 21254004

  • Peg V, Espinosa-Bravo M, Vieites B, Vilardell F, Antunez JR, de Salas MS, Delgado-Sanchez JJ, Pinto W, Gozalbo F, Petit A, Sansano I, Del Mar Tellez M, Rubio IT. Intraoperative molecular analysis of total tumor load in sentinel lymph node: a new predictor of axillary status in early breast cancer patients. Breast Cancer Res Treat. 2013 May;139(1):87-93. doi: 10.1007/s10549-013-2524-z. Epub 2013 Apr 11.

    PubMed 23576079

  • Veronesi U, Orecchia R, Zurrida S, Galimberti V, Luini A, Veronesi P, Gatti G, D'Aiuto G, Cataliotti L, Paolucci R, Piccolo P, Massaioli N, Sismondi P, Rulli A, Lo Sardo F, Recalcati A, Terribile D, Acerbi A, Rotmensz N, Maisonneuve P. Avoiding axillary dissection in breast cancer surgery: a randomized trial to assess the role of axillary radiotherapy. Ann Oncol. 2005 Mar;16(3):383-8. doi: 10.1093/annonc/mdi089. Epub 2005 Jan 24.

    PubMed 15668261

  • Martelli G, Boracchi P, De Palo M, Pilotti S, Oriana S, Zucali R, Daidone MG, De Palo G. A randomized trial comparing axillary dissection to no axillary dissection in older patients with T1N0 breast cancer: results after 5 years of follow-up. Ann Surg. 2005 Jul;242(1):1-6; discussion 7-9. doi: 10.1097/01.sla.0000167759.15670.14.

    PubMed 15973094

  • Hwang RF, Gonzalez-Angulo AM, Yi M, Buchholz TA, Meric-Bernstam F, Kuerer HM, Babiera GV, Tereffe W, Liu DD, Hunt KK. Low locoregional failure rates in selected breast cancer patients with tumor-positive sentinel lymph nodes who do not undergo completion axillary dissection. Cancer. 2007 Aug 15;110(4):723-30. doi: 10.1002/cncr.22847.

    PubMed 17587208

  • Bilimoria KY, Bentrem DJ, Hansen NM, Bethke KP, Rademaker AW, Ko CY, Winchester DP, Winchester DJ. Comparison of sentinel lymph node biopsy alone and completion axillary lymph node dissection for node-positive breast cancer. J Clin Oncol. 2009 Jun 20;27(18):2946-53. doi: 10.1200/JCO.2008.19.5750. Epub 2009 Apr 13.

    PubMed 19364968

  • Veronesi U, Viale G, Paganelli G, Zurrida S, Luini A, Galimberti V, Veronesi P, Intra M, Maisonneuve P, Zucca F, Gatti G, Mazzarol G, De Cicco C, Vezzoli D. Sentinel lymph node biopsy in breast cancer: ten-year results of a randomized controlled study. Ann Surg. 2010 Apr;251(4):595-600. doi: 10.1097/SLA.0b013e3181c0e92a.

    PubMed 20195151

  • Caudle AS, Hunt KK, Kuerer HM, Meric-Bernstam F, Lucci A, Bedrosian I, Babiera GV, Hwang RF, Ross MI, Feig BW, Hoffman K, Litton JK, Sahin AA, Yang W, Hortobagyi GN, Buchholz TA, Mittendorf EA. Multidisciplinary considerations in the implementation of the findings from the American College of Surgeons Oncology Group (ACOSOG) Z0011 study: a practice-changing trial. Ann Surg Oncol. 2011 Sep;18(9):2407-12. doi: 10.1245/s10434-011-1593-7. No abstract available.

    PubMed 21327455

  • Giuliano AE, McCall L, Beitsch P, Whitworth PW, Blumencranz P, Leitch AM, Saha S, Hunt KK, Morrow M, Ballman K. Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases: the American College of Surgeons Oncology Group Z0011 randomized trial. Ann Surg. 2010 Sep;252(3):426-32; discussion 432-3. doi: 10.1097/SLA.0b013e3181f08f32.

    PubMed 20739842

  • Giuliano AE, Hunt KK, Ballman KV, Beitsch PD, Whitworth PW, Blumencranz PW, Leitch AM, Saha S, McCall LM, Morrow M. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA. 2011 Feb 9;305(6):569-75. doi: 10.1001/jama.2011.90.

    PubMed 21304082

Questions about this trial

What is this clinical trial studying?

A study testing Irradiation in people with Breast Cancer, run by Grupo de Investigación Clínica en Oncología Radioterapia at 50 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 50 sites in Spain, Portugal, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Disease Free Survival (time frame: 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02335957, which also lists 21 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2022.

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