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Improved Breast Cancer Therapy (I-BCT-1) in the Neoadjuvant and Metastatic Setting

Primary Purpose

Breast Cancer

Status

Active

Phase

Phase 2

Locations

Norway

Study Type

Interventional

Intervention

Carboplatin

Paclitaxel

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring locally advanced breast cancer, metastatic breast cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Written informed consent obtained prior to any study-specific procedure
Female or male age ≥ 18 years
Able to comply with the protocol
Histologically or cytologically confirmed, HER2 (human epidermal growth factor 2) -negative, men or women with breast adenocarcinoma
WHO performance status ≤ 2
Adequate hematological function Absolute neutrophil count (ANC) ≥1.0 x 109/L AND Platelet count ≥100 x 109/L AND Hemoglobin ≥ 10 g/dL (may be transfused to maintain or exceed this level)
Adequate liver function Total bilirubin <1.5 x upper limit of normal (ULN) AND AST (aspartate aminotransferase), ALT (alanine aminotransferase) <2.5 x ULN (in cohort I); AST, ALT <5 x ULN (in cohort II)
Adequate renal function Serum creatinine ≤1.25 x ULN (and if measured: Creatinine clearance within normal reference values)
Women should not be pregnant or breast-feeding. Women with an intact uterus (unless amenorrhoeic for the last 24 months and premenopausal levels of FSH (follicle stimulating hormone), LH (luteinizing hormone) and oestradiol) must have a negative serum pregnancy test within 28 days prior to inclusion into the study.

Exclusion Criteria:

Previous chemotherapy treatment for localized breast cancer less than 24 months before inclusion into study (cohort I) or metastatic breast cancer treated with taxane (cohort II).
Other earlier or concomitant carcinoma less than five years prior to the breast cancer diagnosis, except for basal cell carcinoma, in situ cervix cancer or breast cancer
Clinically significant (i.e. active) cardiovascular disease for example cardiovascular accident (≤6 months before enrolment), myocardial infarction (≤6 months before enrolment), unstable angina, congestive heart failure (CHF) NYHA (New York Heart Association) Class ≥II, serious cardiac arrhythmia requiring medication during the study, which might interfere with regularity of the study treatment, or not controlled by medication
Treatment with any other investigational agent, or participation in another clinical intervention trial within 21 days prior to enrolment
Evidence of any other disease, neurological or metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment-related complications.

Sites / Locations

Oslo University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Control

Additional therapy

Arm Description

Paclitaxel 80 mg/m2 weekly for 12 weeks, thereafter current standard chemotherapy for 12 weeks

Carboplatin AUC 6 (area under curve; mg/ml/min) once every 3 weeks, for 12 weeks. Paclitaxel 80 mg/m2 weekly for 12 weeks, thereafter current standard chemotherapy for 12 weeks

Outcomes

Primary Outcome Measures

Treatment response: Cohort I - pCR (pathologic complete response), Cohort II - CR (complete response), PR (partial response), SD (stable disease), PD (progressive disease)

The primary objective of the study is to determine the molecular (DNA, RNA, protein and metabolic) changes in the tumors with reference to the obtained therapeutic response in the different treatment arms.

Secondary Outcome Measures

Circulating tumor-DNA in plasma

Treatment induced changes and characteristics of circulating tumor DNA compared to tumor response

Fatigue (patient reported by standardized questionnaire)

Course of fatigue and predictors of chronic fatigue in the treatment arms.

Full Information

NCT ID

NCT02546232

First Posted

August 11, 2015

Last Updated

October 3, 2023

Sponsor

Oslo University Hospital

1. Study Identification

Unique Protocol Identification Number

NCT02546232

Brief Title

Improved Breast Cancer Therapy (I-BCT-1) in the Neoadjuvant and Metastatic Setting

Official Title

Improved Breast Cancer Therapy (I-BCT-1) in the Neoadjuvant and Metastatic Setting: A Phase 2 Clinical Trial Protocol Studying Biological Rationale for the Optimal Selection of Treatment Regimens

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

April 1, 2015 (Actual)

Primary Completion Date

December 31, 2021 (Actual)

Study Completion Date

December 31, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Oslo University Hospital

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of the study is to investigate the molecular biology of the tumor in relation to treatment response to chemotherapy, in particular paclitaxel compared to the combination paclitaxel and carboplatin. The study is carried out in two different, separate cohorts: Cohort I: Patients with large primary breast cancer (> 2.0 cm) including locally advanced disease, are treated with weekly paclitaxel for 12 weeks, before continuing on anthracycline containing regimen for another 12 weeks before surgery. Patient are randomized 1:1 to receive carboplatin in addition to paclitaxel for the first 12 weeks of the treatment. Cohort II: Patients with metastatic disease, available for biopsies before and during therapy are included to receive paclitaxel for 24 weeks. Patients are randomized 1:1 to receive paclitaxel alone or paclitaxel in combination with carboplatin.

Detailed Description

High-throughput methods in molecular biology have revealed considerable alterations in the breast cancer genome, transcriptome and proteome with extensive heterogeneity between tumors, potentially explaining the large variation in response to treatment. Classification of breast cancer can be based on such molecular alterations, and have shown to be of clinical relevance. Studies on how genome-wide mRNA (messenger ribonucleic acid) /miRNA (microRNA) expression, copy number alterations (CNAs) and DNA methylation, in addition to the detection of circulating tumor DNA could be used to improve prognostication and aid in therapy decision are highly needed. This project includes a phase II clinical trial where patients will be randomized to treatment with standard anthracycline- and taxane containing chemotherapy with or without the addition of carboplatin. The study aims to include patients in two cohorts as described, with large primary breast cancer (cohort I - 150 patients) and patients with metastatic disease (cohort II - 60 patients). Essential for the study is the mandatory tissue samples for comprehensive molecular analyses to identify markers of response.

6. Conditions and Keywords

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

Breast Cancer

Keywords

locally advanced breast cancer, metastatic breast cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

196 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Control

Arm Type

Active Comparator

Arm Description

Paclitaxel 80 mg/m2 weekly for 12 weeks, thereafter current standard chemotherapy for 12 weeks

Arm Title

Additional therapy

Arm Type

Experimental

Arm Description

Carboplatin AUC 6 (area under curve; mg/ml/min) once every 3 weeks, for 12 weeks. Paclitaxel 80 mg/m2 weekly for 12 weeks, thereafter current standard chemotherapy for 12 weeks

Intervention Type

Drug

Intervention Name(s)

Carboplatin

Intervention Description

Chemotherapy

Intervention Type

Drug

Intervention Name(s)

Paclitaxel

Other Intervention Name(s)

Taxol

Intervention Description

Chemotherapy

Primary Outcome Measure Information:

Title

Treatment response: Cohort I - pCR (pathologic complete response), Cohort II - CR (complete response), PR (partial response), SD (stable disease), PD (progressive disease)

Description

Time Frame

24 weeks

Secondary Outcome Measure Information:

Title

Circulating tumor-DNA in plasma

Description

Treatment induced changes and characteristics of circulating tumor DNA compared to tumor response

Time Frame

24 weeks

Title

Fatigue (patient reported by standardized questionnaire)

Description

Course of fatigue and predictors of chronic fatigue in the treatment arms.

Time Frame

24 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Written informed consent obtained prior to any study-specific procedure Female or male age ≥ 18 years Able to comply with the protocol Histologically or cytologically confirmed, HER2 (human epidermal growth factor 2) -negative, men or women with breast adenocarcinoma WHO performance status ≤ 2 Adequate hematological function Absolute neutrophil count (ANC) ≥1.0 x 109/L AND Platelet count ≥100 x 109/L AND Hemoglobin ≥ 10 g/dL (may be transfused to maintain or exceed this level) Adequate liver function Total bilirubin <1.5 x upper limit of normal (ULN) AND AST (aspartate aminotransferase), ALT (alanine aminotransferase) <2.5 x ULN (in cohort I); AST, ALT <5 x ULN (in cohort II) Adequate renal function Serum creatinine ≤1.25 x ULN (and if measured: Creatinine clearance within normal reference values) Women should not be pregnant or breast-feeding. Women with an intact uterus (unless amenorrhoeic for the last 24 months and premenopausal levels of FSH (follicle stimulating hormone), LH (luteinizing hormone) and oestradiol) must have a negative serum pregnancy test within 28 days prior to inclusion into the study. Exclusion Criteria: Previous chemotherapy treatment for localized breast cancer less than 24 months before inclusion into study (cohort I) or metastatic breast cancer treated with taxane (cohort II). Other earlier or concomitant carcinoma less than five years prior to the breast cancer diagnosis, except for basal cell carcinoma, in situ cervix cancer or breast cancer Clinically significant (i.e. active) cardiovascular disease for example cardiovascular accident (≤6 months before enrolment), myocardial infarction (≤6 months before enrolment), unstable angina, congestive heart failure (CHF) NYHA (New York Heart Association) Class ≥II, serious cardiac arrhythmia requiring medication during the study, which might interfere with regularity of the study treatment, or not controlled by medication Treatment with any other investigational agent, or participation in another clinical intervention trial within 21 days prior to enrolment Evidence of any other disease, neurological or metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment-related complications.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Olav Engebraaten, MD, PhD

Organizational Affiliation

Department of Oncology, Oslo University Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Oslo University Hospital

City

Oslo

Country

Norway

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Improved Breast Cancer Therapy (I-BCT-1) in the Neoadjuvant and Metastatic Setting

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