Genomics Guided Targeted Post-neoadjuvant Therapy in Patients With Early Breast Cancer (COGNITION-GUIDE)
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|ClinicalTrials.gov Identifier: NCT05332561|
Recruitment Status : Not yet recruiting
First Posted : April 18, 2022
Last Update Posted : September 14, 2022
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.
|Condition or disease||Intervention/treatment||Phase|
|Early-stage Breast Cancer||Drug: Atezolizumab 1200 mg in 20 ML Injection Drug: Inavolisib Drug: Ipatasertib Drug: Olaparib Drug: Sacituzumab govitecan Drug: Trastuzumab/pertuzumab||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||240 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Umbrella|
|Masking:||None (Open Label)|
|Official Title:||Genomics Guided Targeted Post-neoadjuvant Therapy in Patients With Early Breast Cancer - a Multicenter, Open-label, Umbrella Phase-II Study - COGNITION-GUIDE|
|Estimated Study Start Date :||December 2022|
|Estimated Primary Completion Date :||April 2029|
|Estimated Study Completion Date :||December 2029|
Experimental: Arm 1 Atezolizumab (Immune Evasion)
Atezolizumab Dosage: 1200 mg, intravenous, on d1, q21d
Drug: Atezolizumab 1200 mg in 20 ML Injection
Other Name: Tecentriq
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
Other Name: Lynparza
Experimental: Arm 5 Sacituzumab Govitecan (TROP-2)
Sacituzumab Govitecan Dosage: 10 mg/kg BW, intravenous, on d1 and d8, q21d
Drug: Sacituzumab govitecan
Other Name: Trodelvy
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
Other Name: Phesgo
No Intervention: Arm 7 Observation
- 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 ]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)
- Invasive Disease-free Survival (IDFS) as defined by Hudis et al [ Time Frame: Four years after surgery ]in each study arm separately
- Distant Disease-free Survival (DDFS) as defined by Hudis et al [ Time Frame: Four years after surgery ]in each study arm separately and overall
- Overall Survival [ Time Frame: When the last patient has completed four years after surgery ]in each study arm separately and overall
- Incidence of Treatment-Emergent Adverse Events (safety and tolerability) [ Time Frame: Through treatment period of the study, an average of 1 year ]in each study arm separately and overall
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05332561
|Contact: Andreas Schneeweiss, Prof. Dr.||+49(0)622156 ext email@example.com|
|Contact: Richard Schlenk, Prof. Dr.||firstname.lastname@example.org|
|National Center for Tumor Diseases|
|Heidelberg, Baden-Wuerttemberg, Germany, 69120|
|Contact: Andreas Schneeweiss, Prof. Dr. email@example.com|
|Principal Investigator:||Andreas Schneeweiss, Prof. Dr.||National Center for Tumor Diseases (NCT)|