Clinical Trials /

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

NCT02546232

Description:

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.

Related Conditions:
  • Breast Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: I-BCT-1
  • NCT ID: NCT02546232

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
CarboplatinAdditional therapy
PaclitaxelTaxolAdditional therapy

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
ControlActive ComparatorPaclitaxel 80 mg/m2 weekly for 12 weeks, thereafter current standard chemotherapy for 12 weeks
  • Paclitaxel
Additional therapyExperimentalCarboplatin 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
  • Carboplatin
  • Paclitaxel

Eligibility Criteria

        Inclusion Criteria:

          1. Written informed consent obtained prior to any study-specific procedure

          2. Female or male age ≥ 18 years

          3. Able to comply with the protocol

          4. Histologically or cytologically confirmed, HER2 (human epidermal growth factor 2)
             -negative, men or women with breast adenocarcinoma

          5. WHO performance status ≤ 2

          6. 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)

          7. 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)

          8. Adequate renal function Serum creatinine ≤1.25 x ULN (and if measured: Creatinine
             clearance within normal reference values)

          9. 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:

          1. 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).

          2. 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

          3. 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

          4. Treatment with any other investigational agent, or participation in another clinical
             intervention trial within 21 days prior to enrolment

          5. 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Treatment response: Cohort I - pCR (pathologic complete response), Cohort II - CR (complete response), PR (partial response), SD (stable disease), PD (progressive disease)
Time Frame:24 weeks
Safety Issue:
Description: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

Measure:Circulating tumor-DNA in plasma
Time Frame:24 weeks
Safety Issue:
Description:Treatment induced changes and characteristics of circulating tumor DNA compared to tumor response
Measure:Fatigue (patient reported by standardized questionnaire)
Time Frame:24 weeks
Safety Issue:
Description:Course of fatigue and predictors of chronic fatigue in the treatment arms.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Oslo University Hospital

Trial Keywords

  • locally advanced breast cancer
  • metastatic breast cancer

Last Updated

February 25, 2019