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Breast CancerOPTIMALIIaNCT03972696

OPTimizing Irradiation Through Molecular Assesment of Lymph Node After Primary Systemic Treatment

A study testing Irradiation in people with Breast Cancer, run by Grupo de Investigación Clínica en Oncología Radioterapia at 20 sites in Spain.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Breast cancer management integrating surgery, systemic therapy and radiation therapy tends to systemic treatment as the first therapeutic option, continuing afterwards by surgery and radiation therapy with the scope of decreasing the locoregional treatment. 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
32 participants
Where
20 sitesSpain
Study dates
Jan 2017to 30 Apr 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 carcinoma of the breast.
  • Metastatic lymph nodes (N1) at diagnosis, as determined histologically by Fine Needle Aspiration or Core Needle Biopsy.
  • Primary systemic therapy (including antiestrogen or chemotherapy, and targeted therapies).
  • Tumour surgery: tumorectomy, quadrantectomy or mastectomy.
  • OSNA (ND) or - lymph nodes after primary systemic therapy.
  • Age ≥ 18 years old.
  • Karnofsky Index ≥ 70 %.
  • Signed Informed Consent.

Who cannot join

  • Lymphadenectomy.
  • Bilateral breast cancer.
  • Males.
  • Previous thoracic irradiation therapy.
  • Contraindications of radiotherapy (pregnancy, severe collagen diseases).
  • Other neoplasms.
Show all 10Show fewer
  • Severe associated comorbidities that, according to the investigator criteria, may interfere with the study evaluations.
  • Lymp nodes OSNA -(L), +, ++ after primary systemic therapy.
  • Sentinel lymph node biopsy previous to the primary systemic therapy.
  • Mammary internal chain affected.

Trial locations and contacts

20 sites in 1 country.

20 sites in 1 country

Spain20 sites

  • Centro Oncológico de Galicia

    A Coruña

  • Hospital Infanta Cristina

    Badajoz

  • ICO Badalona

    Badalona

  • Hospital Universitario de Cruces

    Barakaldo, Bilbao

  • Hospital Universitario Santa Lucía

    Cartagena

  • Hospital Universitario de Donostia

    Donostia / San Sebastian

  • ICO Girona

    Girona

  • Hospital Universitari Arnau de Vilanova

    Lleida

  • Hospital Clínico San Carlos

    Madrid

  • Hospital Universitario Fundación Jiménez Díaz

    Madrid

  • Hospital Universitario Gregrorio Marañón

    Madrid

  • Hospital Universitario La Paz

    Madrid

  • Hospital Universitario Ramón y Cajal

    Madrid

  • Hospital Universitario Virgen de la Victoria

    Málaga

  • Hospital Universitario Virgen de la Arrixaca

    Murcia

  • Hospital Universitario Sant Joan de Reus

    Reus, Tarragona

  • Hospital Universitario Virgen de la Macarena

    Seville

  • Hospital Universitario Virgen del Rocío

    Seville

  • Hospital General Universitario de Valencia

    Valencia

  • Hospital Universitario de Araba

    Vitoria-Gasteiz, Basque Country

Other trials in Spain

About this study

Breast cancer management integrating surgery, systemic therapy and radiation therapy tends to systemic treatment as the first therapeutic option, continuing afterwards by surgery and radiation therapy with the scope of decreasing the locoregional treatment. This strategy implies doubts about what should be the locoregional treatment, because many patients have remissions and a significant number of them a complete response. The responses are associated with better clinical outcome although there are doubts about they are a surrogate marker of survival.

Nodal irradiation after systemic treatment in patients with breast cancer it is under discussion, particularly in the case of patients with initial clinical involvement experiencing complete remission. For this reason, some groups decide irradiation of all nodal regions and others choose no irradiation of the lymph nodes at all. To clarify this discussion the present study is proposed.

Read more

The "One Step Nucleic Amplification" (OSNA) is a technique developed by Sysmex Corporation that allows a complete analysis of sentinel nodes and provides a quantification of the tumor marker Cytokeratin 19 (CK19) messenger ribonucleic acid (mRNA) in the sentinel node. The result is expressed by the Tumour Load as number of copies per microliter. This technique has shown its diagnostic ability both without primary systemic treatment and after primary systemic treatment, being more reproducible than conventional processes.

In spite of this, fits to mention that the studies of validation used to obtain the European Conformity (CE) mark only included patients without previous systemic treatment to the surgery.

Read the detailed description

Breast cancer management integrating surgery, systemic therapy and radiation therapy tends to systemic treatment as the first therapeutic option, continuing afterwards by surgery and radiation therapy with the scope of decreasing the locoregional treatment. This strategy implies doubts about what should be the locoregional treatment, because many patients have remissions and a significant number of them a complete response. The responses are associated with better clinical outcome although there are doubts about they are a surrogate marker of survival.

According to a previous publication, in which the predictors of locoregional recurrence National Surgical Adjuvant Breast and Bowel Project 18 (NSABP18) and National Surgical Adjuvant Breast and Bowel Project 27 (NSABP27) studies are evaluated, both studies designed for viewing the value of neoadjuvant chemotherapy, good results of locoregional control are described, although in many cases radiotherapy was omitted or lymph node were not irradiated.

Therefore the need to nodal irradiation begins to be questioned, especially when they are negative after primary systemic treatment, regardless of their previous state. However the clinical guidelines recommend radiotherapy planning according to the previous stage. The problem is the local treatment indication is established based on the indications of irradiation without primary systemic therapy, as showed in retrospective studies, without the existence of randomized studies designed to analyze the role of radiotherapy in these circumstances. In the last American Society of Clinical Oncology (ASCO) preliminary results of a meta-analysis including three large studies of primary systemic treatment were presented.

Results show that irradiation improves local control in N1 patients achieving a complete remission, radiotherapy being an independent prognostic factor, in terms of locoregional control; however, they conclude that the optimal selection of patients remains unclear. The controversy remains, because there is no evidence to treat nodes after primary systemic therapy, whether there is a complete remission as if it does not, nor is it known that subgroup of patients may benefit more from local treatments. Long-term studies are needed to analyze this issue, leaving the decision being especially complicated in cases of clinically positive nodes experiencing a complete remission. The problem remains that often is not known exactly has been irradiated since, in many studies, irradiation is indicated at the discretion of the researcher.

Given these doubts, European Society conducted a survey to find out what was the attitude about these patients, and the findings shows that 75% of the centers irradiate in the N1 case. The American Society obtained similar results and in Spain 64% of respondents irradiate the lymph nodes. These three publications conclude that studies are needed to determine the importance of irradiation after primary systemic treatment and while waiting for these results, a consensus muts be reached as stated in ASCO 2015 summary.

The "One Step Nucleic Amplification" (OSNA) is a technique developed by Sysmex Corporation that allows a complete analysis of sentinel nodes and provides a quantification of the tumor marker CK19 mRNA in the sentinel node. The result is expressed by the Tumour Load as number of copies per microliter. This technique has shown its diagnostic ability both without primary systemic treatment and after primary systemic treatment, being more reproducible than conventional processes.

In spite of this, fits to mention that the studies of validation used to obtain the CE mark only included patients without previous systemic treatment to the surgery.

In summary, nodal irradiation after systemic treatment in patients with breast cancer it is under discussion, particularly in the case of patients with initial clinical involvement experiencing complete remission. For this reason, some groups decide irradiation of all nodal regions and others choose no irradiation of the lymph nodes at all. To clarify this discussion the present study is proposed.

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

    BA3S versus BA2 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 NCT03972696
Study groupRoleWhat they receive
BA3SActive comparatorRadiotherapy (RT) will be administered, in the breast or thoracic wall, axillary levels I, II and III, and supraclavicular node areas, with optimization of the technique Intentional irradiation of lymph nodes: Patients 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
BA2ExperimentalRT will be administered, in the breast or thoracic wall and axillary levels I and II, with optimization of the technique Incidental irradiation of lymph nodes: Patients 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. To show the non-inferiority of (BA2) compared to (BA3S), in terms of 5-years diseasefree survival (DFS), including the local, regional and distant disease free survival and excluding second neoplasms

    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 (3)

  1. To compare the 5-years incidence of loco-regional tumor recurrence between BA2 and BA3S.

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

    Measured: 5 Years

  2. To compare the 5-years incidence of distant tumor recurrence between BA2 and BA3S

    Distant recurrence rate occurring during the 5-years follow-up, 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 or internal mammary chain.

    Measured: 5 years

  3. To compare the acute and chronic toxicity of the two treatment modalities.

    Toxicity, recorded using the Terminology Criteria for Adverse Events v4.0 (CTCAE).

    Measured: 5 years

Timeline

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

  1. First posted4 Jun 2019
  2. Study startJan 2017
  3. Primary completion30 Apr 2021
  4. Study completion30 Apr 2021

Why it stopped: The inclusion rate of patients is too slow, so it is not possible to reach the estimated N.

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
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03972696
Sponsor's protocol ID
GIC-RAD-2016-01
Acronym
OPTIMALIIa
Status last verified
Sep 2021
First submitted
31 May 2019
Last updated
1 Nov 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, Bonnefoi H, Cameron D, Gianni L, Valagussa P, Swain SM, Prowell T, Loibl S, Wickerham DL, Bogaerts J, Baselga J, Perou C, Blumenthal G, Blohmer J, Mamounas EP, Bergh J, Semiglazov V, Justice R, Eidtmann H, Paik S, Piccart M, Sridhara R, Fasching PA, Slaets L, Tang S, Gerber B, Geyer CE Jr, Pazdur R, Ditsch N, Rastogi P, Eiermann W, von Minckwitz G. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014 Jul 12;384(9938):164-72. doi: 10.1016/S0140-6736(13)62422-8. Epub 2014 Feb 14.

    PubMed 24529560

  • Mamounas EP, Anderson SJ, Dignam JJ, Bear HD, Julian TB, Geyer CE Jr, Taghian A, Wickerham DL, Wolmark N. Predictors of locoregional recurrence after neoadjuvant chemotherapy: results from combined analysis of National Surgical Adjuvant Breast and Bowel Project B-18 and B-27. J Clin Oncol. 2012 Nov 10;30(32):3960-6. doi: 10.1200/JCO.2011.40.8369. Epub 2012 Oct 1.

    PubMed 23032615

  • Noh JM, Park W, Suh CO, Keum KC, Kim YB, Shin KH, Kim K, Chie EK, Ha SW, Kim SS, Ahn SD, Shin HS, Kim JH, Lee HS, Lee NK, Huh SJ, Choi DH. Is elective nodal irradiation beneficial in patients with pathologically negative lymph nodes after neoadjuvant chemotherapy and breast-conserving surgery for clinical stage II-III breast cancer? A multicentre retrospective study (KROG 12-05). Br J Cancer. 2014 Mar 18;110(6):1420-6. doi: 10.1038/bjc.2014.26. Epub 2014 Jan 30.

    PubMed 24481403

  • Shim SJ, Park W, Huh SJ, Choi DH, Shin KH, Lee NK, Suh CO, Keum KC, Kim YB, Ahn SD, Kim SS, Ha SW, Chie EK, Kim K, Shin HS, Kim JH, Lee HS. The role of postmastectomy radiation therapy after neoadjuvant chemotherapy in clinical stage II-III breast cancer patients with pN0: a multicenter, retrospective study (KROG 12-05). Int J Radiat Oncol Biol Phys. 2014 Jan 1;88(1):65-72. doi: 10.1016/j.ijrobp.2013.09.021. Epub 2013 Oct 22.

    PubMed 24161425

  • Nagar H, Boothe D, Ginter PS, Sison C, Vahdat L, Shin S, Smith M, Chao KS, Nori D, Hayes MK. Disease-free survival according to the use of postmastectomy radiation therapy after neoadjuvant chemotherapy. Clin Breast Cancer. 2015 Apr;15(2):128-34. doi: 10.1016/j.clbc.2014.09.012. Epub 2014 Nov 11.

    PubMed 25459070

  • Bernier J. Post-mastectomy radiotherapy after neodjuvant chemotherapy in breast cancer patients: A review. Crit Rev Oncol Hematol. 2015 Mar;93(3):180-9. doi: 10.1016/j.critrevonc.2014.10.011. Epub 2014 Oct 31.

    PubMed 25465740

  • White J, Mamounas E. Locoregional radiotherapy in patients with breast cancer responding to neoadjuvant chemotherapy: a paradigm for treatment individualization. J Clin Oncol. 2014 Feb 20;32(6):494-5. doi: 10.1200/JCO.2013.53.4974. Epub 2013 Dec 30. No abstract available.

    PubMed 24378411

  • Marks LB, Prosnitz LR. Reducing local therapy in patients responding to preoperative systemic therapy: are we outsmarting ourselves? J Clin Oncol. 2014 Feb 20;32(6):491-3. doi: 10.1200/JCO.2013.51.3523. Epub 2013 Dec 30. No abstract available.

    PubMed 24378409

  • Smith BD. Using chemotherapy response to personalize choices regarding locoregional therapy: a new era in breast cancer treatment? J Clin Oncol. 2012 Nov 10;30(32):3913-5. doi: 10.1200/JCO.2012.44.4539. Epub 2012 Oct 1. No abstract available.

    PubMed 23032624

  • Mamounas EP. Impact of neoadjuvant chemotherapy on locoregional surgical treatment of breast cancer. Ann Surg Oncol. 2015 May;22(5):1425-33. doi: 10.1245/s10434-015-4406-6. Epub 2015 Mar 2.

    PubMed 25727558

  • Rusthoven CG, Rabinovitch RA, Jones BL, Koshy M, Amini A, Yeh N, Jackson MW, Fisher CM. The impact of postmastectomy and regional nodal radiation after neoadjuvant chemotherapy for clinically lymph node-positive breast cancer: a National Cancer Database (NCDB) analysis. Ann Oncol. 2016 May;27(5):818-27. doi: 10.1093/annonc/mdw046. Epub 2016 Feb 9.

    PubMed 26861597

  • Belkacemi Y, Kaidar-Person O, Poortmans P, Ozsahin M, Valli MC, Russell N, Kunkler I, Hermans J, Kuten A, van Tienhoven G, Westenberg H; Breast Working Party of the EORTC Radiation Oncology Group (ROG). Patterns of practice of regional nodal irradiation in breast cancer: results of the European Organization for Research and Treatment of Cancer (EORTC) NOdal Radiotherapy (NORA) survey. Ann Oncol. 2015 Mar;26(3):529-35. doi: 10.1093/annonc/mdu561. Epub 2014 Dec 5.

    PubMed 25480875

  • Haffty BG, McCall LM, Ballman KV, McLaughlin S, Jagsi R, Ollila DW, Hunt KK, Buchholz TA, Boughey JC. Patterns of Local-Regional Management Following Neoadjuvant Chemotherapy in Breast Cancer: Results From ACOSOG Z1071 (Alliance). Int J Radiat Oncol Biol Phys. 2016 Mar 1;94(3):493-502. doi: 10.1016/j.ijrobp.2015.11.005. Epub 2015 Nov 10.

    PubMed 26867878

  • Arenas M, Montero A, de Las Penas MD, Algara M. The position and current status of radiation therapy after primary systemic therapy in breast cancer: a national survey-based expert consensus statement. Clin Transl Oncol. 2016 Jun;18(6):582-91. doi: 10.1007/s12094-015-1401-0. Epub 2015 Sep 14.

    PubMed 26370420

  • Dizon DS, Krilov L, Cohen E, Gangadhar T, Ganz PA, Hensing TA, Hunger S, Krishnamurthi SS, Lassman AB, Markham MJ, Mayer E, Neuss M, Pal SK, Richardson LC, Schilsky R, Schwartz GK, Spriggs DR, Villalona-Calero MA, Villani G, Masters G. Clinical Cancer Advances 2016: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology. J Clin Oncol. 2016 Mar 20;34(9):987-1011. doi: 10.1200/JCO.2015.65.8427. Epub 2016 Feb 4. No abstract available.

    PubMed 26846975

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 20 sites in Spain.

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 8 inclusion and 10 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: stopped early, as of the sponsor's last update on 1 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in Spain. 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 was stopped early (reason given: The inclusion rate of patients is too slow, so it is not possible to reach the estimated N.). Results are not available in the source record.

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?

To show the non-inferiority of (BA2) compared to (BA3S), in terms of 5-years diseasefree survival (DFS), including the local, regional and distant disease free survival and excluding second neoplasms (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 NCT03972696, 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 Nov 2021.

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