Safe De-escalation of Chemotherapy for Stage 1 Breast Cancer

NCT05058183 | Recruiting

• 1 other identifier: CCR5348
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 2

Brief Summary

The aim of this study is to assess the rates of circulating tumour DNA (ctDNA) in patients treated with surgery for stage 1 breast cancer that is HER2 positive or triple negative. The study will involve collecting blood samples from patients before and after surgery, if patients are enrolled after surgery, blood samples will be collected after the procedure. On the follow-up visit, the results obtained from the blood tests will serve as a diagnostic method to discern adverse outcomes in the groups of patients with positive and negative ctDNA detection. Also, the results obtained will aid physicians in determining treatment courses for patients, in order to reduce the intensity of adjuvant chemotherapy. By identifying the patients with residual disease with ctDNA analysis, it is possible that this will improve disease prognosis.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Incidence of patients with ctDNA detection treated with surgery for stage 1 breast cancer

  Blood samples will be analysed for the presence of circulating tumour DNA using the standard clinical Signatera assay.

  2 to 4 weeks post surgery.

Secondary Outcomes (5)

• Relapse free survival

  Through study completion, minimum 5 years unless early study termination.

• Proportion of physicians who change treatment advice

  Up to 6 weeks post surgery.

• Distant recurrence free survival

  Through study completion, minimum 5 years unless early study termination.

• Invasive disease free survival

  Through study completion, minimum 5 years unless early study termination.

• Overall survival

  Through study completion, minimum 5 years unless early study termination.

Study Arms (1)

All participants

EXPERIMENTAL

All participants

Diagnostic Test: ctDNA

Interventions

ctDNA DIAGNOSTIC_TEST

Patients with stage 1 HER2 positive and triple negative breast cancer will receive ctDNA test after surgery. Treating clinicians will receive results and may change treatment plans in event of negative test.

All participants

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years or older.
• Patients with histologically confirmed breast cancer that is either
• A) HER2 positive as defined by 2018 ASCO-CAP guidelines determined by local testing B) Triple negative defined as ER negative (ER staining in \<1% tumour cells or ER Allred score \<3/8) and PR negative (PR staining in \<10% tumour cells or PR Allred score \<6/8) and HER2 negative by 2018 ASCO-CAP guidelines determined by local testing. Patients without PR testing results may enrol on the basis of ER and HER2 results.
• Note that patients negative for ER and PR may enrol whilst awaiting HER2 testing results
• Stage 1 cancer excluding pT1aN0 cancer, defined as
• A) Patients prior to surgery with primary tumour size on imaging 6-20mm and a normal axilla ultrasound or a biopsy negative axilla
• Patients who enrol prior to surgery will only continue further testing in the trial if their pathological staging fits the after surgery criteria.
• B) Patients after surgery with either
• Primary tumour size pT1b or pT1c (6-20mm) and pN0 or pN1mi (micrometastasis).
• Primary tumour size pT1a (1-5mm) and pN1mi
• Note that patients consenting after surgery may not enrol with pT1aN0 stage disease
• Patients should consent prior to surgery (preferred) or within 2 weeks of surgery. Patients who consent after surgery may extend consent to 4 weeks after surgery, although this will delay the receipt of ctDNA results.
• Planned and fit enough to receive full standard post-operative chemotherapy, with HER2 targeting as appropriate.
• Ability to give informed consent and comply with study procedures including blood tests and follow-up for five years.

You may not qualify if:

• Distant metastatic disease.
• Multifocal invasive cancer
• Diagnosis of alternative cancer within the last 5 years other than resected non-melanoma skin cancer or cervical intraepithelial neoplasia.
• Any prior treatment (including neo-adjuvant chemotherapy) for the current breast cancer with the exception of surgical resection for patients enrolling after surgery.
• Known HIV or hepatitis B or hepatitis C infection.

Sponsors & Collaborators

• Royal Marsden NHS Foundation Trust: lead
• Massachusetts General Hospital: collaborator
• Natera, Inc.: collaborator

Study Sites (2)

The Royal Marsden NHS Foundation Trust, Chelsea

London, SW3 6JJ, United Kingdom

RECRUITING

The Royal Marsden NHS Foundation Trust, Sutton

Sutton, SM5 5PT, United Kingdom

RECRUITING

Related Publications (13)

• Abbosh C, Birkbak NJ, Wilson GA, Jamal-Hanjani M, Constantin T, Salari R, Le Quesne J, Moore DA, Veeriah S, Rosenthal R, Marafioti T, Kirkizlar E, Watkins TBK, McGranahan N, Ward S, Martinson L, Riley J, Fraioli F, Al Bakir M, Gronroos E, Zambrana F, Endozo R, Bi WL, Fennessy FM, Sponer N, Johnson D, Laycock J, Shafi S, Czyzewska-Khan J, Rowan A, Chambers T, Matthews N, Turajlic S, Hiley C, Lee SM, Forster MD, Ahmad T, Falzon M, Borg E, Lawrence D, Hayward M, Kolvekar S, Panagiotopoulos N, Janes SM, Thakrar R, Ahmed A, Blackhall F, Summers Y, Hafez D, Naik A, Ganguly A, Kareht S, Shah R, Joseph L, Marie Quinn A, Crosbie PA, Naidu B, Middleton G, Langman G, Trotter S, Nicolson M, Remmen H, Kerr K, Chetty M, Gomersall L, Fennell DA, Nakas A, Rathinam S, Anand G, Khan S, Russell P, Ezhil V, Ismail B, Irvin-Sellers M, Prakash V, Lester JF, Kornaszewska M, Attanoos R, Adams H, Davies H, Oukrif D, Akarca AU, Hartley JA, Lowe HL, Lock S, Iles N, Bell H, Ngai Y, Elgar G, Szallasi Z, Schwarz RF, Herrero J, Stewart A, Quezada SA, Peggs KS, Van Loo P, Dive C, Lin CJ, Rabinowitz M, Aerts HJWL, Hackshaw A, Shaw JA, Zimmermann BG; TRACERx consortium; PEACE consortium; Swanton C. Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution. Nature. 2017 Apr 26;545(7655):446-451. doi: 10.1038/nature22364.

  PMID: 28445469 BACKGROUND

• Coombes RC, Page K, Salari R, Hastings RK, Armstrong A, Ahmed S, Ali S, Cleator S, Kenny L, Stebbing J, Rutherford M, Sethi H, Boydell A, Swenerton R, Fernandez-Garcia D, Gleason KLT, Goddard K, Guttery DS, Assaf ZJ, Wu HT, Natarajan P, Moore DA, Primrose L, Dashner S, Tin AS, Balcioglu M, Srinivasan R, Shchegrova SV, Olson A, Hafez D, Billings P, Aleshin A, Rehman F, Toghill BJ, Hills A, Louie MC, Lin CJ, Zimmermann BG, Shaw JA. Personalized Detection of Circulating Tumor DNA Antedates Breast Cancer Metastatic Recurrence. Clin Cancer Res. 2019 Jul 15;25(14):4255-4263. doi: 10.1158/1078-0432.CCR-18-3663. Epub 2019 Apr 16.

  PMID: 30992300 BACKGROUND

• Early Breast Cancer Trialists' Collaborative Group (EBCTCG); Peto R, Davies C, Godwin J, Gray R, Pan HC, Clarke M, Cutter D, Darby S, McGale P, Taylor C, Wang YC, Bergh J, Di Leo A, Albain K, Swain S, Piccart M, Pritchard K. Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet. 2012 Feb 4;379(9814):432-44. doi: 10.1016/S0140-6736(11)61625-5. Epub 2011 Dec 5.

  PMID: 22152853 BACKGROUND

• Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005 May 14-20;365(9472):1687-717. doi: 10.1016/S0140-6736(05)66544-0.

  PMID: 15894097 BACKGROUND

• Garcia-Murillas I, Chopra N, Comino-Mendez I, Beaney M, Tovey H, Cutts RJ, Swift C, Kriplani D, Afentakis M, Hrebien S, Walsh-Crestani G, Barry P, Johnston SRD, Ring A, Bliss J, Russell S, Evans A, Skene A, Wheatley D, Dowsett M, Smith IE, Turner NC. Assessment of Molecular Relapse Detection in Early-Stage Breast Cancer. JAMA Oncol. 2019 Oct 1;5(10):1473-1478. doi: 10.1001/jamaoncol.2019.1838.

  PMID: 31369045 BACKGROUND

• Garcia-Murillas I, Schiavon G, Weigelt B, Ng C, Hrebien S, Cutts RJ, Cheang M, Osin P, Nerurkar A, Kozarewa I, Garrido JA, Dowsett M, Reis-Filho JS, Smith IE, Turner NC. Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer. Sci Transl Med. 2015 Aug 26;7(302):302ra133. doi: 10.1126/scitranslmed.aab0021.

  PMID: 26311728 BACKGROUND

• Jones S, Holmes FA, O'Shaughnessy J, Blum JL, Vukelja SJ, McIntyre KJ, Pippen JE, Bordelon JH, Kirby RL, Sandbach J, Hyman WJ, Richards DA, Mennel RG, Boehm KA, Meyer WG, Asmar L, Mackey D, Riedel S, Muss H, Savin MA. Docetaxel With Cyclophosphamide Is Associated With an Overall Survival Benefit Compared With Doxorubicin and Cyclophosphamide: 7-Year Follow-Up of US Oncology Research Trial 9735. J Clin Oncol. 2009 Mar 10;27(8):1177-83. doi: 10.1200/JCO.2008.18.4028. Epub 2009 Feb 9.

  PMID: 19204201 BACKGROUND

• Loibl S, O'Shaughnessy J, Untch M, Sikov WM, Rugo HS, McKee MD, Huober J, Golshan M, von Minckwitz G, Maag D, Sullivan D, Wolmark N, McIntyre K, Ponce Lorenzo JJ, Metzger Filho O, Rastogi P, Symmans WF, Liu X, Geyer CE Jr. Addition of the PARP inhibitor veliparib plus carboplatin or carboplatin alone to standard neoadjuvant chemotherapy in triple-negative breast cancer (BrighTNess): a randomised, phase 3 trial. Lancet Oncol. 2018 Apr;19(4):497-509. doi: 10.1016/S1470-2045(18)30111-6. Epub 2018 Feb 28.

  PMID: 29501363 BACKGROUND

• Reinert T, Henriksen TV, Christensen E, Sharma S, Salari R, Sethi H, Knudsen M, Nordentoft I, Wu HT, Tin AS, Heilskov Rasmussen M, Vang S, Shchegrova S, Frydendahl Boll Johansen A, Srinivasan R, Assaf Z, Balcioglu M, Olson A, Dashner S, Hafez D, Navarro S, Goel S, Rabinowitz M, Billings P, Sigurjonsson S, Dyrskjot L, Swenerton R, Aleshin A, Laurberg S, Husted Madsen A, Kannerup AS, Stribolt K, Palmelund Krag S, Iversen LH, Gotschalck Sunesen K, Lin CJ, Zimmermann BG, Lindbjerg Andersen C. Analysis of Plasma Cell-Free DNA by Ultradeep Sequencing in Patients With Stages I to III Colorectal Cancer. JAMA Oncol. 2019 Aug 1;5(8):1124-1131. doi: 10.1001/jamaoncol.2019.0528.

  PMID: 31070691 BACKGROUND

• Tie J, Wang Y, Tomasetti C, Li L, Springer S, Kinde I, Silliman N, Tacey M, Wong HL, Christie M, Kosmider S, Skinner I, Wong R, Steel M, Tran B, Desai J, Jones I, Haydon A, Hayes T, Price TJ, Strausberg RL, Diaz LA Jr, Papadopoulos N, Kinzler KW, Vogelstein B, Gibbs P. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer. Sci Transl Med. 2016 Jul 6;8(346):346ra92. doi: 10.1126/scitranslmed.aaf6219.

  PMID: 27384348 BACKGROUND

• Tolaney SM, Barry WT, Dang CT, Yardley DA, Moy B, Marcom PK, Albain KS, Rugo HS, Ellis M, Shapira I, Wolff AC, Carey LA, Overmoyer BA, Partridge AH, Guo H, Hudis CA, Krop IE, Burstein HJ, Winer EP. Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer. N Engl J Med. 2015 Jan 8;372(2):134-41. doi: 10.1056/NEJMoa1406281.

  PMID: 25564897 BACKGROUND

• Tolaney SM, Guo H, Pernas S, Barry WT, Dillon DA, Ritterhouse L, Schneider BP, Shen F, Fuhrman K, Baltay M, Dang CT, Yardley DA, Moy B, Marcom PK, Albain KS, Rugo HS, Ellis MJ, Shapira I, Wolff AC, Carey LA, Overmoyer B, Partridge AH, Hudis CA, Krop IE, Burstein HJ, Winer EP. Seven-Year Follow-Up Analysis of Adjuvant Paclitaxel and Trastuzumab Trial for Node-Negative, Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer. J Clin Oncol. 2019 Aug 1;37(22):1868-1875. doi: 10.1200/JCO.19.00066. Epub 2019 Apr 2.

  PMID: 30939096 BACKGROUND

• von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. doi: 10.1056/NEJMoa1703643. Epub 2017 Jun 5.

  PMID: 28581356 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Nicholas Turner

  Royal Marsden NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Project Manager

CONTACT

020 7808 2887; SAFE-DE@rmh.nhs.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study is looking into the ctDNA diagnostic test, this is given after breast cancer surgery to see whether patient is clear from cancer

Study Record Dates

• First Submitted: August 19, 2021
• First Posted: September 27, 2021
• Study Start: June 5, 2023
• Primary Completion: December 5, 2025
• Study Completion (Estimated): December 5, 2028
• Last Updated: June 22, 2023

Record last verified: 2023-06

Locations

GB (2)