Genomics Guided Targeted Post-neoadjuvant Therapy in Patients With Early Breast Cancer (COGNITION-GUIDE)

NCT05332561 | Recruiting Phase 2 DMC

• 4 other identifiers: DKFZ-2019-0082020-002606-2201EK2202A2024-514022-23-00
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 9

Brief Summary

In early breast cancer (eBC), pathological complete response (pCR) after neoadjuvant therapy acts as surrogate marker for metastasis and overall survival. Therapy intensification by adding an adjuvant therapy line (post-neoadjuvant treatment) substantially lowers the risk of relapse in high-risk breast cancer patients with residual disease after neoadjuvant treatment (non-pCR). While this approach was exemplified in two phase III trials without biomarker-stratification (CREATE-X, KATHERINE), even higher efficiency might be achieved by individualized genomic-guided post-neoadjuvant therapies. Within the seven-arm umbrella phase-II clinical trial COGNITION-GUIDE, we aim to deliver molecularly-tailored cancer care by implementing an additional response- and genomics-guided post-neoadjuvant therapy after finishing the guideline-compliant post-neoadjuvant treatment in high-risk breast cancer patients with residual cancer burden after neoadjuvant therapy to reduce the substantial risk of local and distant relapse. The trial evaluates not a single drug but rather a general strategy of precision oncology in the curative setting and provides the basis for future confirmatory biomarker-driven trials. Allocation to the therapy-arms is conducted by in depth molecular characterization of tumors within the COGNITION registry program. The study aims to show an overall benefit of the precision medicine approach in high-risk eBC patients and to allow for secondary exploratory evaluation of each study-arm. The primary endpoint of the study is invasive Disease-Free Survival (IDFS) after 4 years measured from surgery to local or distant relapse or death. The sample size of the entire trial is 240 eligible patients.

Conditions

Early-stage Breast Cancer

Keywords

Breast Cancer; Post-neoadjuvant therapy; genomics-guided; molecular diagnostic; targeted therapy; high risk

Outcome Measures

Primary Outcomes (1)

• Invasive Disease-free Survival (IDFS) as defined by Hudis et al in the entire study population four years after surgery

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

  Four years after surgery

Secondary Outcomes (4)

• Invasive Disease-free Survival (IDFS) as defined by Hudis et al

  Four years after surgery

• Distant Disease-free Survival (DDFS) as defined by Hudis et al

  Four years after surgery

• Overall Survival

  When the last patient has completed four years after surgery

• Incidence of Treatment-Emergent Adverse Events (safety and tolerability)

  Through treatment period of the study, an average of 1 year

Study Arms (7)

Arm 1 Atezolizumab (Immune Evasion)

EXPERIMENTAL

Atezolizumab Dosage: 1200 mg, intravenous, on d1, q21d

Drug: Atezolizumab 1200 mg in 20 ML Injection

Arm 2 Inavolisib (PI3K)

EXPERIMENTAL

Inavolisib Dosage: 9 mg, oral, on d1-d28, q28d

Drug: Inavolisib

Arm 3 Ipatasertib (AKT)

EXPERIMENTAL

Ipatasertib Dosage: 400 mg, oral, on d1-d21, q28d

Drug: Ipatasertib

Arm 4 Olaparib (PARP, DNA-Repair)

EXPERIMENTAL

Olaparib Dosage: 300 mg, oral, bid d1-d28, q28d

Drug: Olaparib

Arm 5 Sacituzumab Govitecan (TROP-2)

EXPERIMENTAL

Sacituzumab Govitecan Dosage: 10 mg/kg BW, intravenous, on d1 and d8, q21d

Drug: Sacituzumab govitecan

Arm 6 Trastuzumab/Pertuzumab (ERBBB)

EXPERIMENTAL

Trastuzumab/Pertuzumab Administration: subcutaneous; Initial dose: Trastuzumab 600 mg, Pertuzumab 1200 mg, 30 000 units hyaluronidase; Maintainance dose: Trastuzumab 600 mg, Pertuzumab 600 mg, 20 000 units hyaluronidase; Frequency: on d1, q21d

Drug: Trastuzumab/pertuzumab

Arm 7 Observation

NO INTERVENTION

Observation

Interventions

Atezolizumab 1200 mg in 20 ML Injection DRUG

Arm 1

Also known as: Tecentriq

Arm 1 Atezolizumab (Immune Evasion)

Inavolisib DRUG

Arm 2

Arm 2 Inavolisib (PI3K)

Ipatasertib DRUG

Arm 3

Arm 3 Ipatasertib (AKT)

Olaparib DRUG

Arm 4

Also known as: Lynparza

Arm 4 Olaparib (PARP, DNA-Repair)

Sacituzumab govitecan DRUG

Arm 5

Also known as: Trodelvy

Arm 5 Sacituzumab Govitecan (TROP-2)

Trastuzumab/pertuzumab DRUG

Arm 6

Also known as: Phesgo

Arm 6 Trastuzumab/Pertuzumab (ERBBB)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of written informed consent
• Female and male patients with non-metastatic early (stage I-III) breast cancer aged ≥ 18 years
• Conducted neoadjuvant chemotherapy and surgery as well as conducted standard post-neoadjuvant treatment +/- radiotherapy (standard according to German guidelines except Abemaciclib and Olaparib)
• For patients with initially triple negative (TNBC) or HER2-positive breast cancer:
• Non-pCR defined as other than ypT0/is ypN0
• For patients with initially hormone receptor positive and HER2-negative breast cancer: Non-pCR and CPS-EG score
• ≥ 3 and ypN0, or
• ≥ 2 and ypN+
• ECOG Performance Status ≤ 1
• 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
• 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
• Evidence of childbearing potential is defined as fertile, following menarche and until becoming post-menopausal unless permanently sterile
• Postmenopausal or evidence of non-childbearing status is defined as:
• Amenorrhea for 1 year or more without an alternative medical cause following cessation of exogenous hormonal treatments plus follicle stimulating hormone (FSH) levels in the postmenopausal range in women not using hormonal contraception or hormonal replacement therapy
• Chemotherapy-induced menopause

You may not qualify if:

• 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
• Concurrent severe, uncontrolled systemic disease that would place patient at undue risk or interfere with planned treatment
• Concurrent participation or previous treatment within 30 days in another interventional clinical trial
• Persistent toxicity (≥ Grade 2 according to NCI CTCAE v5.0 caused by previous cancer therapy, excluding alopecia
• Clinical signs of active infection (\> Grade 2 according NCI CTCAE v5.0)
• History of or newly diagnosed human immunodeficiency virus (HIV) infection and immunocompromised patients
• Active Hepatitis A virus infection
• 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
• 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
• Dementia or significant impairment of cognitive state
• Epilepsy requiring pharmacologic treatment
• Pregnancy and breast feeding
• Inability to take oral medication and gastrointestinal disorders likely to interfere with absorption of study medication
• 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
• Systemic chemotherapy or radiotherapy within four weeks or a longer period depending on the characteristics of the agents used

Sponsors & Collaborators

• German Cancer Research Center: lead

Study Sites (9)

National Center for Tumor Diseases

Heidelberg, Baden-Wurttemberg, 69120, Germany

RECRUITING

Universitätsklinikum Tübingen

Tübingen, Baden-Wurttemberg, 72076, Germany

RECRUITING

Universitätsklinikum Augsburg

Augsburg, Bavaria, 86156, Germany

RECRUITING

Universitätsklinikum Erlangen

Erlangen, Bavaria, 91054, Germany

RECRUITING

Universitätsklinikum Ulm

Ulm, Bavaria, 89075, Germany

RECRUITING

Universitätsklinikum Würzburg

Würzburg, Bavaria, 97080, Germany

NOT YET RECRUITING

Universitätsklinikum Carl-Gustav-Carus

Dresden, Saxony, 01397, Germany

RECRUITING

Charité - Universitätsmedizin Berlin

Berlin, Germany

RECRUITING

Universitätsklinikum Essen

Essen, 45147, Germany

NOT YET RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

atezolizumab; Injections; inavolisib; ipatasertib; olaparib; sacituzumab govitecan; Trastuzumab; pertuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Andreas Schneeweiss, Prof. Dr.

  National Center for Tumor Diseases (NCT)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andreas Schneeweiss, Prof. Dr.

CONTACT

+49(0)622156; andreas.schneeweiss@med.uni-heidelberg.de

Richard Schlenk, Prof. Dr.

CONTACT

richard.schlenk@nct-heidelberg.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Umbrella

Study Record Dates

• First Submitted: March 22, 2022
• First Posted: April 18, 2022
• Study Start: June 29, 2023
• Primary Completion (Estimated): March 1, 2030
• Study Completion (Estimated): December 1, 2030
• Last Updated: March 20, 2025

Record last verified: 2025-02

Locations

DE (9)