MicroRNA Profiles in Triple Negative Breast Cancer

NCT04771871 | Recruiting Phase 2 DMC

• 1 other identifier: UI-ROD-OCTU02
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 4

Brief Summary

Triple negative breast cancer (TNBC) is an aggressive disease with higher proportion of Blacks affected and in younger age groups. There is no targeted therapy unlike other types of breast cancer such as hormone positive and Human Epidermal Growth factor 2 (HER2) positive subtypes. Chemotherapy is therefore the main choice of systemic treatment with rapid development of resistance in most cases. At present, there is no blood test to monitor treatment response and disease relapse. This one-stage phase II study with a single arm design will determine the response rate of standard chemotherapy using Epirubicin (60mg/m2), Cyclophosphamide (600mg/m2) , Paclitaxel (120mg/m2) and Carboplatin (6AUC) in TNBC patients. We will measure the blood level of microRNA molecules and circulating tumor DNA during and after treatment to test if changes can be used to indicate drug failure in these patients. Disease status and tumor response will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) guidelines while toxicity will be assessed using CTCAE v5). The trial will be conducted as per the International Council on Harmonisation Good Clinical Practice (ICH GCP) Guidelines E6 (R1) and other applicable guidelines

Conditions

Triple Negative Breast Cancer

Keywords

Breast cancer; neoadjuvant treatment; microRNA; circulating tumor cells

Outcome Measures

Primary Outcomes (2)

• Number of participants achieving pathological complete response (pCR) at surgery following neoadjuvant treatment with epirubicin + cyclophosphamide every three weeks for four cycles followed by paclitaxel + carboplatin every three weeks for four cycles

  Percentage of participants achieving pathological complete response (pCR) at surgery

  4 - 6 months from commencement of chemotherapy. (Surgery will be performed within 4-6 weeks after completion of chemotherapy

• Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0

  Percentage of participants experiencing grades 3 and 4 hematological, gastro-intestinal, neurological and cardiovascular toxicities.

  From the date of commencement of chemotherapy till date of first documentation of adverse event up to 60 months or withdrawal or death from any cause or which ever occurs first.

Secondary Outcomes (2)

• Number of Participants without disease for 2 , 5 and 10 years respectively

  From date of first dose of study drug treatment up to a maximum of 120 months years.

• Change in quality of life (QoL) score of patients from baseline using the EORTC quality of life questionnaire during chemotherapy and at study completion

  From date of commencement of study medications up to 60 months

Other Outcomes (1)

• The serum levels of circulating microRNAs during chemotherapy in TNBC. To explore mechanisms of resistance to chemotherapy in Nigerian women with TNBC

  From date of commencement of chemotherapy up to 24 weeks

Study Arms (1)

Epirubicin-Cyclophosphamide plus Paclitaxel- Carboplatin

EXPERIMENTAL

Epirubicin 60mg/m2 with cyclophosphamide 600/m2 every three weeks for four courses followed by paclitaxel 120mg/m2 and carboplatin 6 AUC every three weeks for four courses

Drug: Epirubicin; Drug: Cyclophosphamide; Drug: Paclitaxel; Drug: Carboplatin

Interventions

Epirubicin DRUG

Epirubicin is an antitumor antibiotics with good activity on breast cancer. It has less cardiotoxic effect than doxorubicin

Also known as: Pharmorubicin, Taxol, Paraplatin, Cytoxan

Epirubicin-Cyclophosphamide plus Paclitaxel- Carboplatin

Cyclophosphamide DRUG

Cyclophosphamide is a cytoxic drug indicated for the treatment of many malignancies including breast cancer

Also known as: Cytoxan

Epirubicin-Cyclophosphamide plus Paclitaxel- Carboplatin

Paclitaxel DRUG

Paclitaxel is a taxane chemotherapy agent indicated for the treatment of many cancers including breast cancer. It can be used alone or in combination with other drugs

Also known as: Taxol

Epirubicin-Cyclophosphamide plus Paclitaxel- Carboplatin

Carboplatin DRUG

Carboplatin is a platinum compound indicated for the treatment of many types of malignancies including breast cancer

Also known as: Carboplat, Paraplatin

Epirubicin-Cyclophosphamide plus Paclitaxel- Carboplatin

Eligibility Criteria

• Age: 18 Years - 70 Years
• Gender Eligibility Details: Bilogical females will be used. This is because female breast are larger with measurable tumor sizes. In addition, microRNA expression will be more uniform in females for this study
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women ages of 18 to 70 years old
• Women who give informed consent for the study
• Biopsy-accessible breast tumor of significant size for core needle biopsy/ultrasound measurable (≥ 2cm)
• Patients with histologically confirmed carcinoma of the female breast with triple negative status by immuno-histochemistry (IHC)
• Clinical stages IIA -IIIC (AJCC 2009)
• Chemotherapy-naïve patients (for this malignancy)
• Performance status: Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Non-pregnant and not nursing. Women of childbearing potential must take the pregnancy test and must commit to receive Leuteinizing Hormone Realising Hormone (LHRH) agonist Zoladex (goserelin) for two years starting from the commencement of the study medications
• Required Initial Laboratory Data. Adequate hematologic, renal and hepatic function, as defined by each of the following:
• \. Granulocyte ≥ 1,500/μL 2. Platelet count ≥ 100,000/μL 3. Absolute neutrophil count (ANC) ≥ l500/μL 4. Hemoglobin ≥ 10g/dL 5. Bilirubin ≤ 1.5 x upper limit of normal 6. SGOT and SGPT \< 2.5 x upper limit of normal 7. Creatinine within institutional normal limits or glomerular filtration rate ≥ 30 mL/min/1.73 m2 by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) (CKD EPI) equation (see http://mdrd.com/ for calculator) 10. Echocardiogram (ECHO): Baseline left ventricular ejection fraction of ≥ 55%

You may not qualify if:

• Pregnant or lactating women. Women of childbearing potential not using a reliable and appropriate contraceptive method. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential.
• Patients with distant metastasis (brain and/or visceral metastasis)
• Serious, uncontrolled, concurrent infection(s).
• Treatment for other carcinomas within the last 5 years, except non-melanoma skin cancer and treated cervical carcinoma in-situ (CCIS)
• Participation in any investigational drug study within 4 weeks preceding the start of study treatment
• Other serious uncontrolled medical conditions that the investigator feels might compromise study participation including but not limited to chronic or active infection, HIV-positive patient, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled Diabetes mellitus, or psychiatric illness/social situations that would limit compliance with study requirements.

Sponsors & Collaborators

• University College Hospital, Ibadan: lead
• Lagos State University: collaborator
• Obafemi Awolowo University Teaching Hospital: collaborator
• University of Chicago: collaborator
• University of Lagos, Nigeria: collaborator
• University of Ibadan: collaborator

Study Sites (4)

Obafemi Awolowo University Teaching Hospital

Ile-Ife, Oshun, Nigeria

NOT YET RECRUITING

University College Hospital

Ibadan, Oyo State, 200221, Nigeria

RECRUITING

Lagos State University Teaching Hospital

Lagos, Nigeria

NOT YET RECRUITING

Lagos University Teaching Hospital

Lagos, Nigeria

NOT YET RECRUITING

Related Publications (4)

• Adalsteinsson VA, Ha G, Freeman SS, Choudhury AD, Stover DG, Parsons HA, Gydush G, Reed SC, Rotem D, Rhoades J, Loginov D, Livitz D, Rosebrock D, Leshchiner I, Kim J, Stewart C, Rosenberg M, Francis JM, Zhang CZ, Cohen O, Oh C, Ding H, Polak P, Lloyd M, Mahmud S, Helvie K, Merrill MS, Santiago RA, O'Connor EP, Jeong SH, Leeson R, Barry RM, Kramkowski JF, Zhang Z, Polacek L, Lohr JG, Schleicher M, Lipscomb E, Saltzman A, Oliver NM, Marini L, Waks AG, Harshman LC, Tolaney SM, Van Allen EM, Winer EP, Lin NU, Nakabayashi M, Taplin ME, Johannessen CM, Garraway LA, Golub TR, Boehm JS, Wagle N, Getz G, Love JC, Meyerson M. Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors. Nat Commun. 2017 Nov 6;8(1):1324. doi: 10.1038/s41467-017-00965-y.

  PMID: 29109393 BACKGROUND

• Aebi S, Davidson T, Gruber G, Cardoso F; ESMO Guidelines Working Group. Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2011 Sep;22 Suppl 6:vi12-24. doi: 10.1093/annonc/mdr371. No abstract available.

  PMID: 21908498 BACKGROUND

• Kaufmann M, von Minckwitz G, Mamounas EP, Cameron D, Carey LA, Cristofanilli M, Denkert C, Eiermann W, Gnant M, Harris JR, Karn T, Liedtke C, Mauri D, Rouzier R, Ruckhaeberle E, Semiglazov V, Symmans WF, Tutt A, Pusztai L. Recommendations from an international consensus conference on the current status and future of neoadjuvant systemic therapy in primary breast cancer. Ann Surg Oncol. 2012 May;19(5):1508-16. doi: 10.1245/s10434-011-2108-2. Epub 2011 Dec 23.

  PMID: 22193884 BACKGROUND

• Mauri D, Pavlidis N, Ioannidis JP. Neoadjuvant versus adjuvant systemic treatment in breast cancer: a meta-analysis. J Natl Cancer Inst. 2005 Feb 2;97(3):188-94. doi: 10.1093/jnci/dji021.

  PMID: 15687361 BACKGROUND

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Breast Neoplasms; Neoplastic Cells, Circulating

Interventions

Epirubicin; Paclitaxel; Carboplatin; Cyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplasm Metastasis; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Coordination Complexes; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Study Officials

• Olufunmilayo I. Olopade

  University of Chicago

  STUDY CHAIR

• Atara Ntekim

  University of Ibadan

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tonyin Aniagwu

CONTACT

234-8033535370; taniagwu@yahoo.com

Abiodun Oni

CONTACT

2348023941587; abiodunoni41@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Study Principal Investigator

Model Details: This is a one-stage phase II study with a single arm design. All patients will receive 4 cycles of epirubicin + cyclophosphamide followed by paclitaxel +carboplatin for four cycles in the neo-adjuvant setting. Those with clinical response (assessed via breast ultrasound), will undergo surgery. After surgery, all patients who achieve pCR will undergo radiotherapy. Patients with pathological incomplete response or stable disease may have additional chemotherapy at the discretion of the managing physician.

Study Record Dates

• First Submitted: February 14, 2021
• First Posted: February 25, 2021
• Study Start: November 29, 2021
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): August 1, 2030
• Last Updated: May 7, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Immediately following publication. No end date
• Access Criteria: As per publishing Journal's policy

Locations

NG (4)