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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Oslo University Hospital HF

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Pathological Conditions, Signs and Symptoms [C23]

Trial duration

10 Sep 2024 → ongoing

Decision date (initial)

2024-09-09

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-515087-31-00

EudraCT number

2013-004418-17

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To determine the genomic (DNA) state and changes over time in the tumors; the genetic characteristics and changes in the tumors will be evaluated by analyses of tumor samples taken before, under (if possible) and after the scheduled treatment period using DNA analyses (including whole genome SNP and methylation analyses or whole genome sequencing).

Secondary objectives 5

1. Analyse the molecular changes in the protein kinase expression as measured by protein tissue arrays, protein arrays and protein kinase activity and mRNA/miRNA expression in the different treatment groups, as measured by RNA microarray analyses or RNA sequencing.
2. Analyse the molecular changes in the metabolome as measured by High resolution MR magnetic angle spinning (HR-MAS) analyses.
3. Analysis of the characteristics of circulating tumor-DNA in plasma samples, circulating tumor cells (CTC) in peripheral blood, at the time points for the tumor sampling with comparison to the tumor analysis and according to the different treatment arms.
4. Analyse the course of fatigue during different treatment regimens and predictors of chronic fatigue after treatment.
5. Adequate liver function

Conditions and MedDRA coding

Breast cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Histologically or cytologically confirmed, HER2-negative, men or women with breast adenocarcinoma with radiologic measureable disease (>20 mm) and Ki67 labeling index ≥ 20% in patients with T2 tumor and ≥ 15% in patients with T3 or T4 tumors.
2. WHO performance status ≤ 2
3. 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)
4. Adequate liver function: Total bilirubin <1.5 x upper limit of normal (ULN) and AST, ALT <2.5 x ULN (in cohort I) and AST, ALT <5 x ULN (in cohort II)
5. Adequate renal function: Serum creatinine ≤1.25 x ULN (and if measured: Creatinine clearance within normal reference values).

Exclusion criteria 3

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 BCC, in situ cervix cancer or breast cancer.
3. Treatment with any other investigational agent, or participation in another clinical intervention trial within 21 days prior to enrolment.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The genomic tumor architecture as described by CAAI, and tumor cell heterogeneity before and after treatment as detected and verified by DNA analysis (SNP analysis/sequencing) and quantified by the six CARMA indices.

Secondary endpoints 5

1. The overall change in the expression (the number and the magnitude of change) of mRNA, and protein in the different treatment groups across timepoints.
2. Changes in the metabolite distribution (individual metabolites and magnitude) as measured by HR-MAS in the different treatment groups.
3. Treatment induced changes and characteristics in circulating tumor DNA and circulating tumor cells in peripheral blood compared to tumor response
4. Difference in levels of fatigue between treatment arms.
5. Host-related, tumor-related and treatment-related factors predicting chronic fatigue

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Oslo University Hospital HF

Sponsor organisation

Oslo University Hospital HF

Address

Taarnbygget, Kirkeveien 166 Kirkeveien 166

City

Oslo

Postcode

0450

Country

Norway

Scientific contact point

Organisation

Oslo University Hospital HF

Contact name

Olav Engebråten

Public contact point

Organisation

Oslo University Hospital HF

Contact name

[email protected]

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications