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MicroRNA Profiles in Triple Negative Breast Cancer (TARMAC)

Primary Purpose

Triple Negative Breast Cancer

Status

Recruiting

Phase

Phase 2

Locations

Nigeria

Study Type

Interventional

Intervention

Epirubicin

Cyclophosphamide

Paclitaxel

Carboplatin

About this trial

This is an interventional treatment trial for Triple Negative Breast Cancer focused on measuring Breast cancer, neoadjuvant treatment, microRNA, circulating tumor cells

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

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:

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:

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.

Sites / Locations

Obafemi Awolowo University Teaching Hospital
University College HospitalRecruiting
Lagos State University Teaching Hospital
Lagos University Teaching Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Epirubicin-Cyclophosphamide plus Paclitaxel- Carboplatin

Arm Description

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

Outcomes

Primary Outcome Measures

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

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.

Secondary Outcome Measures

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

Invasive Disease Free Survival (iDFS )

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

The various domains of QoL over time and the changes from baseline using the validated European Organization for Research and Treatment of Cancer (EORTC)) QoL instrument (global and breast module).

Full Information

NCT ID

NCT04771871

First Posted

February 14, 2021

Last Updated

February 16, 2022

Sponsor

University College Hospital, Ibadan

Collaborators

Lagos State University, Obafemi Awolowo University Teaching Hospital, University of Chicago, University of Lagos, Nigeria, University of Ibadan

1. Study Identification

Unique Protocol Identification Number

NCT04771871

Brief Title

MicroRNA Profiles in Triple Negative Breast Cancer

Acronym

TARMAC

Official Title

Treatment Response and microRNA Profiles in Triple Negative Breast Cancer Patients Receiving Standard Chemotherapy

Study Type

Interventional

2. Study Status

Record Verification Date

February 2022

Overall Recruitment Status

Recruiting

Study Start Date

November 29, 2021 (Actual)

Primary Completion Date

March 2023 (Anticipated)

Study Completion Date

August 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University College Hospital, Ibadan

Collaborators

Lagos State University, Obafemi Awolowo University Teaching Hospital, University of Chicago, University of Lagos, Nigeria, University of Ibadan

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Triple Negative Breast Cancer

Keywords

Breast cancer, neoadjuvant treatment, microRNA, circulating tumor cells

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Model Description

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.

Masking

None (Open Label)

Allocation

N/A

Enrollment

42 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Epirubicin-Cyclophosphamide plus Paclitaxel- Carboplatin

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Epirubicin

Other Intervention Name(s)

Pharmorubicin, Taxol, Paraplatin, Cytoxan

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Other Intervention Name(s)

Cytoxan

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Paclitaxel

Other Intervention Name(s)

Taxol

Intervention Description

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

Intervention Name(s)

Carboplatin

Other Intervention Name(s)

Carboplat, Paraplatin

Intervention Description

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

Primary Outcome Measure Information:

Title

Description

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

Time Frame

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

Title

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

Description

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

Time Frame

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 Outcome Measure Information:

Title

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

Description

Invasive Disease Free Survival (iDFS )

Time Frame

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

Title

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

Description

The various domains of QoL over time and the changes from baseline using the validated European Organization for Research and Treatment of Cancer (EORTC)) QoL instrument (global and breast module).

Time Frame

From date of commencement of study medications up to 60 months

Other Pre-specified Outcome Measures:

Title

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

Description

The fold change in serum levels of miRNA during chemotherapy will be determine in TNBC patients before and during each course of chemotherapy.

Time Frame

From date of commencement of chemotherapy up to 24 weeks

10. Eligibility

Sex

Female

Gender Based

Yes

Gender Eligibility Description

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

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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: 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: 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Tonyin Aniagwu

Phone

234-8033535370

taniagwu@yahoo.com

First Name & Middle Initial & Last Name or Official Title & Degree

Abiodun Oni

Phone

2348023941587

abiodunoni41@gmail.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Olufunmilayo I. Olopade

Organizational Affiliation

University of Chicago

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Atara Ntekim

Organizational Affiliation

University of Ibadan

Official's Role

Principal Investigator

Facility Information:

Facility Name

Obafemi Awolowo University Teaching Hospital

City

Ile-Ife

State/Province

Oshun

Country

Nigeria

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ifeoluwa Olagunju

Phone

2347053670305

ifeoluwaolagunju4@gmail.com

First Name & Middle Initial & Last Name & Degree

Olukayode Arowolo, MD

First Name & Middle Initial & Last Name & Degree

Akinwunmi Komolafe, MD

Facility Name

University College Hospital

City

Ibadan

State/Province

Oyo

ZIP/Postal Code

200221

Country

Nigeria

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Tonyin Aniagwu, RN MPH

Phone

234-8033535370

taniagwu@yahoo.com

First Name & Middle Initial & Last Name & Degree

Abiodun Oni, BSc

Phone

2348023941587

abiodunoni41@gmail.com

First Name & Middle Initial & Last Name & Degree

Atara Ntekim, MD

First Name & Middle Initial & Last Name & Degree

Adenike Adeniji-Sofoluwe, MD

First Name & Middle Initial & Last Name & Degree

Ayorinde Folasire, MD

Facility Name

Lagos State University Teaching Hospital

City

Lagos

Country

Nigeria

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Stella O Odedina, PhD

Phone

2348035762998

stellakinleye@yahoo.com

First Name & Middle Initial & Last Name & Degree

Abiodun Popoola, MD

First Name & Middle Initial & Last Name & Degree

Ayodele Sanni, MD

First Name & Middle Initial & Last Name & Degree

Abiola Ibraheem, MD

Facility Name

Lagos University Teaching Hospital

City

Lagos

Country

Nigeria

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ibidunni Akerele

Phone

2347063727006

ibidunniakerele7@gmail.com

First Name & Middle Initial & Last Name & Degree

Anthonia Sowunmi, MD

First Name & Middle Initial & Last Name & Degree

Thomas Olajide

First Name & Middle Initial & Last Name & Degree

Fatima Abdulkareem

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

All of the individual participant data collected during the trial, after deidentification. The data will be deposited with the journal as supplementary data. Access will be as per journals policy

IPD Sharing Time Frame

Immediately following publication. No end date

IPD Sharing Access Criteria

As per publishing Journal's policy

Citations:

PubMed Identifier

29109393

Citation

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.

Results Reference

background

PubMed Identifier

21908498

Citation

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.

Results Reference

background

PubMed Identifier

22193884

Citation

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.

Results Reference

background

PubMed Identifier

15687361

Citation

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.

Results Reference

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MicroRNA Profiles in Triple Negative Breast Cancer

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