MicroRNA Profiles in Triple Negative Breast Cancer

NCT ID: NCT04771871

Last Updated: 2022-02-18

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-29
• Study Completion Date: 2023-08-31

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

Detailed Description

Triple negative subtype of breast cancer (TNBC), accounts for about 55% of all breast cancer among indigenous blacks, such as Nigerians, and younger women are more susceptible Patients with TNBC generally experience a more aggressive clinical course with faster disease progression and poorer overall survival. There is no targeted treatment available beyond conventional cytotoxic chemotherapy . Unfortunately, standard chemotherapy is only effective in about 40% of patients with pathological complete response (pCR) achieved only in 20%-30% . Local relapse occurs early. Therefore, chemo-resistance is the main cause of chemotherapeutic failure and leads to suboptimal response rates . There are no biomarkers of response for close monitoring of TNBC patients to identify chemotherapy failure early. This one-stage phase II study with a single arm is designed to assess the response rate and toxicity of Epirubicin-Cyclophosphamide with Paclitaxel-Carboplatin (ECPC) and examine the potential of using circulating microRNa and circulating tumor cells as a surrogate marker of chemotherapy resistance in Nigerian women with triple negative breast cancer. A total of 42 patients will be enrolled into the trial. Each participant will receive Epirubicin (60mg/m2), Cyclophosphamide (600mg/m2) , Paclitaxel (120mg/m2) and Carboplatin (6AUC) . Blood microRNA and circulating tumor DNA will be determined before and after therapy. Tumor response will be measured by breast ultrasound and described using RECIST criteria while toxicity will be graded using CTCAE criteria. Quality of life (QoL) of participants while on chemotherapy will also be assessed using EORTC quality of life questionnaire - (General and Breast cancer specific).

Conditions

Triple Negative Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Epirubicin-Cyclophosphamide plus Paclitaxel- Carboplatin

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

Group Type: EXPERIMENTAL

Epirubicin

Intervention Type: DRUG

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

Cyclophosphamide

Intervention Type: DRUG

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

Paclitaxel

Intervention Type: 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

Carboplatin

Intervention Type: DRUG

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

Interventions

Epirubicin

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

Intervention Type: DRUG

Cyclophosphamide

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

Intervention Type: DRUG

Paclitaxel

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

Intervention Type: DRUG

Carboplatin

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

Intervention Type: DRUG

Other Intervention Names

Pharmorubicin; Taxol; Paraplatin; Cytoxan; Cytoxan; Taxol; Carboplat; Paraplatin

Eligibility Criteria

Inclusion Criteria

1. Women ages of 18 to 70 years old

2. Women who give informed consent for the study

3. Biopsy-accessible breast tumor of significant size for core needle biopsy/ultrasound measurable (≥ 2cm)

4. Patients with histologically confirmed carcinoma of the female breast with triple negative status by immuno-histochemistry (IHC)

5. Clinical stages IIA -IIIC (AJCC 2009)

6. Chemotherapy-naïve patients (for this malignancy)

7. Performance status: Eastern Cooperative Oncology Group (ECOG) performance status 0-1

8. 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

9. Required Initial Laboratory Data. Adequate hematologic, renal and hepatic function, as defined by each of the following:

1. 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%

Exclusion Criteria

1. 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.

2. Patients with distant metastasis (brain and/or visceral metastasis)

3. Serious, uncontrolled, concurrent infection(s).

4. Treatment for other carcinomas within the last 5 years, except non-melanoma skin cancer and treated cervical carcinoma in-situ (CCIS)

5. Participation in any investigational drug study within 4 weeks preceding the start of study treatment

6. 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Lagos State University

OTHER

Sponsor Role: collaborator

Obafemi Awolowo University Teaching Hospital

OTHER

Sponsor Role: collaborator

University of Chicago

OTHER

Sponsor Role: collaborator

University of Lagos, Nigeria

OTHER

Sponsor Role: collaborator

University of Ibadan

OTHER

Sponsor Role: collaborator

University College Hospital, Ibadan

OTHER

Sponsor Role: lead

Responsible Party

Atara Ntekim

Study Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Olufunmilayo I. Olopade

Role: STUDY_CHAIR

University of Chicago

Atara Ntekim

Role: PRINCIPAL_INVESTIGATOR

University of Ibadan

Locations

Obafemi Awolowo University Teaching Hospital

Ile-Ife, Oshun, Nigeria

Site Status: NOT_YET_RECRUITING

University College Hospital

Ibadan, Oyo State, Nigeria

Site Status: RECRUITING

Lagos State University Teaching Hospital

Lagos, , Nigeria

Site Status: NOT_YET_RECRUITING

Lagos University Teaching Hospital

Lagos, , Nigeria

Site Status: NOT_YET_RECRUITING

Countries

Nigeria

Central Contacts

Tonyin Aniagwu

Role: CONTACT

taniagwu@yahoo.com

234-8033535370

Abiodun Oni

Role: CONTACT

abiodunoni41@gmail.com

2348023941587

Facility Contacts

Ifeoluwa Olagunju

Role: primary

ifeoluwaolagunju4@gmail.com

2347053670305

Tonyin Aniagwu, RN MPH

Role: primary

taniagwu@yahoo.com

234-8033535370

Abiodun Oni, BSc

Role: backup

abiodunoni41@gmail.com

2348023941587

Stella O Odedina, PhD

Role: primary

stellakinleye@yahoo.com

2348035762998

Ibidunni Akerele

Role: primary

ibidunniakerele7@gmail.com

2347063727006

References

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.

Reference Type: BACKGROUND

PMID: 29109393 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21908498 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22193884 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15687361 (View on PubMed)

Other Identifiers

UI-ROD-OCTU02

Identifier Type: -

Identifier Source: org_study_id