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

Sponsor
German Cancer Research Center
Study ID
NCT05332561
Phase
PHASE2
Status
Recruiting
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Conditions

  • Early-stage Breast Cancer

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

Study Details

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.

Key Dates

Start date
Jun 29, 2023
Status verified
Feb 2025
Primary completion
Mar 31, 2030
Completion
Dec 31, 2030

Study Design

Enrollment
240 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Arm 1 Atezolizumab (Immune Evasion)
    Atezolizumab Dosage: 1200 mg, intravenous, on d1, q21d
  • Experimental: Arm 2 Inavolisib (PI3K)
    Inavolisib Dosage: 9 mg, oral, on d1-d28, q28d
  • Experimental: Arm 3 Ipatasertib (AKT)
    Ipatasertib Dosage: 400 mg, oral, on d1-d21, q28d
  • Experimental: Arm 4 Olaparib (PARP, DNA-Repair)
    Olaparib Dosage: 300 mg, oral, bid d1-d28, q28d
  • Experimental: Arm 5 Sacituzumab Govitecan (TROP-2)
    Sacituzumab Govitecan Dosage: 10 mg/kg BW, intravenous, on d1 and d8, q21d
  • Experimental: Arm 6 Trastuzumab/Pertuzumab (ERBBB)
    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
  • No Intervention: Arm 7 Observation
    Observation

Primary Outcome Measure

Invasive Disease-free Survival (IDFS) as defined by Hudis et al in the entire study population four years after surgery [ Time Frame: Four years after surgery ]

Central Contacts

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