Genomics guided targeted post-neoadjuvant therapy in patients with early breast cancer – a multicenter, open-label, umbrella phase-II study (COGNITION-GUIDE)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Deutsches Krebsforschungszentrum Stiftung Des Oeffentlichen Rechts

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

23 Jun 2023 → ongoing

Decision date (initial)

2024-10-09

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-514022-23-00

EudraCT number

2020-002606-22

ClinicalTrials.gov

NCT05332561

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety, Others

To improve clinical outcome in early high-risk breast cancer by biomarker-guided postneoadjuvant therapy (systemic treatment in the adjuvant setting following neoadjuvant therapy, surgery and post-neoadjuvant standard therapy)

Secondary objectives 5

1. To assess Invasive Disease-free Survival (IDFS) as defined by Hudis et al*,1 four years after surgery in each study arm separately
2. To assess Distant Disease-free Survival (DDFS) as defined by Hudis et al four years after surgery
3. To assess overall survival (OS)
4. To assess Safety and tolerability of biomarker-guided post-neoadjuvant treatment in each study arm separately and overall
5. To evaluate feasibility of biomarker-guided post-neoadjuvant treatment

Conditions and MedDRA coding

Early breast cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Provision of written informed consent
2. Female and male patients with non-metastatic early (stage I-III) breast cancer aged ≥ 18 years
3. Conducted neoadjuvant chemotherapy and surgery as well as conducted standard postneoadjuvant treatment +/- radiotherapy (standard according to German guidelines except Abemaciclib and Olaparib)*
4. For patients with initially triple negative (TNBC) or HER2-positive breast cancer: Non-pCR defined as other than ypT0/is ypN0
5. For patients with initially hormone receptor positive and HER2-negative breast cancer: NonpCR and CPS-EG score • ≥ 3 and ypN0, or • ≥ 2 and ypN+
6. ECOG Performance Status ≤ 1
7. Acute effects of any prior therapy resolved to baseline severity or National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0) Grade ≤ 1 except for adverse effects not constituting a safety risk by investigator judgement
8. Postmenopausal or evidence of non-childbearing status. For women of childbearing potential negative urine pregnancy test at post-operative screening and baseline as well as highly effective forms of contraception have to be in place thereafter
9. Female patients of childbearing potential and male patients with partners of childbearing potential who are sexually active must agree to the use of two forms of contraception in combination (male condom and one highly effective method). These should be started immediately after signing the informed consent form and continued throughout the period of study treatment plus a substance-depending time period (see respective sub-protocol) for female patients and a substance-depending time period for male patients. Details on contraception and pregnancy testing for male and female patients (and if indicated their partners) under IMP treatment are described within the respective sub-protocol
10. Ability of patient to understand and comply with the protocol for the duration of the study, including treatment and scheduled visits and examinations
11. Adequate bone marrow, renal, and hepatic function defined by laboratory tests

Exclusion criteria 21

1. Other malignancy within the last 5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), Stage 1 grade 1 endometrial carcinoma, or other solid tumours including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for ≥ 5 year
2. Concurrent severe, uncontrolled systemic disease that would place patient at undue risk or interfere with planned treatment
3. Concurrent participation or previous treatment within 30 days in another interventional clinical trial
4. Persistent toxicity (≥ Grade 2 according to NCI CTCAE v5.0 caused by previous cancer therapy, excluding alopecia
5. Clinical signs of active infection (> Grade 2 according NCI CTCAE v5.0)
6. History of or newly diagnosed human immunodeficiency virus (HIV) infection and immunocompromised patients
7. Active Hepatitis A virus infection
8. Active hepatitis B virus (HBV) infection, defined as having a positive hepatitis B surface antigen (HBsAg) test. Patients with a past or resolved HBV infection, defined as having a negative HBsAg test and a positive total hepatitis B core antibody (HBcAb) test at screening , are eligible for the study if active HBV infection is ruled out on the basis of HBV DNA viral load per local guidelines
9. Active hepatitis C virus (HCV) infection, defined as having a positive HCV antibody test at screening confirmed by a polymerase chain reaction (PCR) positive for HCV RNA
10. Dementia or significant impairment of cognitive state
11. Epilepsy requiring pharmacologic treatment
12. Pregnancy and breast feeding
13. Inability to take oral medication and gastrointestinal disorders likely to interfere with absorption of study medication
14. Major surgery (any invasive operative procedure in which a more extensive resection is performed, e.g. a body cavity is entered, organs are removed, or normal anatomy is altered) within four weeks before screening and baseline excluding breast-tumor resection after neoadjuvant chemotherapy. Patients must have recovered from any effects of any major surgery
15. Systemic chemotherapy or radiotherapy within four weeks or a longer period depending on the characteristics of the agents used
16. Heart failure classified as New York Heart Association (NYHA) II/III/IV
17. Severe obstructive or restrictive ventilation disorder
18. Patients with clinically active tuberculosis
19. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug
20. Is taking or requiring the continued use of any of the prohibited concomitant medications listed in the respective subprotocols at baseline
21. Patients considered a poor medical risk due to a serious, uncontrolled medical disorder or non-malignant systemic disease. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, unstable spinal cord compression or, superior vena cava syndrome

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. IDFS* of patients four years after surgery overall (*IDFS: time from surgery to whatever comes first a) ipsilateral invasive breast tumor recurrence, b) local/regional invasive breast cancer recurrence, c) distant recurrence, d) death attributable to any cause incl. breast cancer, e) contralateral invasive breast cancer or f) Second primary non-breast invasive cancer)

Secondary endpoints 4

1. overall survival (OS)
2. IDFS in each study arm separately
3. time from surgery to whatever comes first a) distant recurrence, b) death attributable to any cause incl. breast cancer or c) second primary non-breast invasive cancer
4. Safety including incidence of adverse events

Investigational products

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

Test 10

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Deutsches Krebsforschungszentrum Stiftung Des Oeffentlichen Rechts

Sponsor organisation

Deutsches Krebsforschungszentrum Stiftung Des Oeffentlichen Rechts

Address

Im Neuenheimer Feld 280, Neuenheim Neuenheim

City

Heidelberg

Postcode

69120

Country

Germany

Scientific contact point

Organisation

Deutsches Krebsforschungszentrum Stiftung Des Oeffentlichen Rechts

Contact name

Prof. Dr. Andreas Schneeweiss

Public contact point

Organisation

Deutsches Krebsforschungszentrum Stiftung Des Oeffentlichen Rechts

Contact name

Luise Strassl

Locations

1 EU/EEA country · 10 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 22 files

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

Application history

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