Estudio KPMNG de Terapia Guiada por Perfiles MOleculares Basada en Alteraciones Genómicas en Tumores Sólidos Avanzados II (KOSMOSII)
Estudio del Grupo de Trabajo en Red de Medicina de Precisión de Corea sobre la Terapia Guiada por Perfiles MOleculares Basada en Alteraciones Genómicas en Tumores Sólidos Avanzados II
A national, prospective, multi-center, open-label, multi-cohort study comprised of a framework to screen patients for actionable targets and evaluation of molecular profiling guided therapy recommended by MTB based on genomic alterations using targeted and/or immunotherapies outside of the approved indications via local clinical practice (Tier 1 & 2) and clinical trials (Tier 3)
Descripción general del estudio
Estado
Condiciones
Descripción detallada
A. The KOSMOS-II study will recruit locally advanced or metastatic solid tumor patients who had disease progression on standard first line anti-cancer treatment and/or has no standard treatment option, in order to prove MTB value to guide treatment within local clinical practice.
B. After site physicians confirm that NGS results of patients are available, they preliminarily decide initial treatment before MTB submission and collect informed consent form, and then patients can register to the KOSMOS-II study. Site physicians upload patients' clinical, pathologic, and genomic data for MTB submission. If site physician cannot determine initial treatment before MTB, site physician can record 'initial treatment cannot be determined' and can register the patient for MTB.
C. MTB records its treatment recommendations within available drugs list based on uploaded data, then site physicians make a final treatment decision, after informing patient about MTB decision and assessment of patients' final health status and preference.
D. Patients who have insufficient genomic information from their NGS results (e.g., lack of variant calling format file or uninterpretable reports) or who are candidates of immunotherapy will submit their tissue and/or blood, for central NGS testing and exploratory biomarker analysis.
E. Recommended treatment option There are three different options including (1) Tier 1: Therapeutic use of investigational products (KOSMOS-II drugs), (2) Tier 2: alternative treatment options, and (3) Tier 3: clinical trials
Tipo de estudio
Inscripción (Actual)
Contactos y Ubicaciones
Ubicaciones de estudio
-
-
-
Bucheon-si, Corea del Sur
- Soonchunhyang University Hospital Bucheon
-
Chungju, Corea del Sur
- Chungbuk National University Hospital
-
Daegu, Corea del Sur
- Keimyung University Dongsan Hospital
-
Daegu, Corea del Sur
- Kyungpook National University Chilgok Hospital
-
Daegu, Corea del Sur
- Yeungnam University Medical Center
-
Daejeon, Corea del Sur
- Chungnam National University Hospital
-
Goyang, Corea del Sur
- National Cancer Center
-
Hwasun, Corea del Sur
- Chonnam National University Hwasun Hospital
-
Incheon, Corea del Sur
- Gachon University Gil Medical Center
-
Incheon, Corea del Sur
- The Catholic University of Korea, Incheon St. Mary's Hospital
-
Jeonju, Corea del Sur
- Jeonbuk National University Hospital
-
Jinju, Corea del Sur
- Gyeongsang National University Hospital
-
Pusan, Corea del Sur
- Dong-A University Hospital
-
Seongnam, Corea del Sur
- Cha University Bundang Medical Center
-
Seongnam, Corea del Sur
- Seoul National University Bundang Hospital
-
Seoul, Corea del Sur
- Asan Medical Center
-
Seoul, Corea del Sur
- Korea University Anam Hospital
-
Seoul, Corea del Sur
- Korea University Guro Hospital
-
Seoul, Corea del Sur
- Samsung Medical Center
-
Seoul, Corea del Sur
- Seoul National University Hospital
-
Seoul, Corea del Sur
- The Catholic University of Korea, Yeouido St. Mary's Hospital
-
Seoul, Corea del Sur
- Gangbuk Samsung Hospital
-
Seoul, Corea del Sur
- Hanyang University Hospital
-
Seoul, Corea del Sur
- Chung-ang University Hospital
-
Seoul, Corea del Sur
- Ewha womans university Mokdong Hospital
-
Seoul, Corea del Sur
- The Catholic University of Korea, Seoul ST. Mary's Hospital
-
Seoul, Corea del Sur
- Yonsei Cancer Hospital
-
Suwon, Corea del Sur
- Ajou University Hospital
-
Suwon, Corea del Sur
- The Catholic University of Korea, ST. Vincent's Hospital
-
Ulsan, Corea del Sur
- Ulsan University Hospital
-
Wŏnju, Corea del Sur
- Wonju Severance Christian Hospital
-
Yangsan, Corea del Sur
- Pusan National University Yangsan Hospital
-
-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Método de muestreo
Población de estudio
Histologically proven locally advanced or metastatic solid tumor patients with disease progression on standard first line anti-cancer treatment and/or has no standard treatment option
Descripción
Inclusion Criteria:
-
19 years of age or older
-
Histologically proven locally advanced or metastatic solid tumors*** who showed disease progression on standard first line anti-cancer treatment and/or has no standard treatment option
*** very rare diseases without standard treatment option which form solid mass, such as Erdheim Chester disease can be enrolled after KOSMOS MTB approval
-
A genomic test results must be available in a MFDS-accredited for laboratories offering service, or in part of clinical trial/study or other commercial labs approved and certified by regulatory bodies compatible with MFDS, such as CLIA. A genomic test can be conducted with tumor tissue as well as plasma circulating tumor DNA.
- Results from genomic profiling tests performed after diagnosis with metastatic/advanced disease to registration are acceptable. NGS results performed within three years prior to registration are preferred. Those patients with NGS results from primary tumor or more than 3 years prior to enrollment can be registered and whether NGS data is acceptable will be subject to MTB decision.
- NGS panels should be i. Tested in a lab that is accredited by one or more quality assurance program (e.g., Korean Institute of Genomic Testing Evaluation, The Korean Society of Pathologists, Korean Society for Laboratory Medicine, Korea Laboratory Accreditation Scheme, etc.) ii. Patients who have insufficient genomic information from their NGS results (e.g., lack of variant calling format file or uninterpretable reports) or who are candidates of immunotherapy will submit their tissue and/or blood, for central NGS testing and exploratory biomarker analysis.
-
Ability to understand and the willingness to sign a written informed consent document
-
Life expectancy of at least 12 weeks
-
Adequate recovery from most recent systemic or local treatment for cancer.
Exclusion Criteria:
- Patients receiving any anti-cancer treatment (local treatment, chemotherapy, immunotherapy, targeted therapy) within 2 weeks prior to the start of study treatment
- Any clinical condition, according to the opinion of site physicians, which makes molecular profiling guided therapy not at the best interest of the participating patient.
- Patients who have ongoing toxicities of ≥ CTCAE 2, other than peripheral neuropathy, related to previous anti-cancer treatment. Patients with ongoing peripheral neuropathy of ≥ CTCAE 3 will be excluded. Laboratory abnormalities ≥ CTCAE 2 considered as not clinically significant by the study physician will be allowed.
- Pregnant or breastfeeding, or intending to become pregnant during the study
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Modelos observacionales: COHORT
- Perspectivas temporales: PROSPECTIVE
Cohortes e Intervenciones
Grupo / Cohorte |
Intervención / Tratamiento |
|---|---|
|
Tier 1. Therapeutic use of investigational products (KOSMOS-II drugs)
If there are no drugs available under current regulation or patients are not feasible to any clinical trials, and If tumors have actionable genetic alterations and approved drug in any indications but tumor type is not indicative, the MTB may recommend one of KOSMOS-II drugs, therapeutic use of investigational products. |
ALK fusion or mutations, Mutations or amplification in any of the following: RET
Otros nombres:
MSI high status by any method Or Any mutation in any of these genes: MLH1 or MSH2 or MSH6 or PMS2 or EPCAM Or Any of the following mutations in POLE: R150X, P286R, P286H, S297F, Y298fs, F367S, V411, L424V, P436R, S459F, R665W, L698fs, R762W, R1519C, R1826W, D316H, D316G, R409W, L474P Or Any of the following mutations in POLD1: P112fs, A930fs, S478N Or Any mutation in the following: POLE not listed above, POLD1 not listed above, POLD2, POLD3, POLD4, POLQ or PRKDC Or Any loss of function mutations in BRCA1, BRCA2, ATM, MSH3, PMS1, MLH3, EXO1, RFC1, RFC2, RFC3, RFC4, RFC5, PCNA, RPA1, PRA2, PRA3, PRA4, or SSBP1 High tumor mutational burden decided by KOSMOS-II MTB (TMB ≥20/Mb in local NGS or if 10-20/Mb, confirmed by central NGS te sting)
Otros nombres:
EGFR Exon 19 deletions in the region E746_E759; Any of the following EGFR mutations: E709A, E709G, E709K, E884K, G719A, G719C, G719S, L858R, L861Q, L833V, S768I
Otros nombres:
ERBB2 amplification, or over-expression; or presence of any of the following ERBB2 mutations: G309A, G309E, S310F, S310Y, R678Q, I655V, D769H, D769Y, L755S, p.L75 5_T759del, I767M, V777L, E321G, R896C; P780ins; delL755-T759 ERBB2 amplification or approved by the KOSMOS Molecular Tumor Board
Otros nombres:
ERBB2 amplification, or over-expression; or presence of any of the following ERBB2 mutations: G309A, G309E, S310F, S310Y, R678Q, I655V, D769H, D769Y,L755S, p.L75 5_T759del, I767M, V777L, E321G, R896C; P780ins; delL755-T759 ERBB2 oncogenic mutations; G152V, X215_splice, D277Y, G292C, N302K, V308M, G309A, S310F, S310Y, S244C, L651V, V659E, G660D, R678Q, V697L, G727A, T733I, L755A, L755P, L755S, D769H, D769Y, A775_G776insSVMA, A775_G776insYVMA (i.e.,Y772_A775dup,M774_A775insAYVME 770delinsEAYVM), G776_V777 > AVCV, G776_V777 > AVGCV, G776_V777 > VCV, G776_V777insVC, G776C, G776delinsLCT, G776L, G776dleinsVC, G776L777_G778insC, V777L, V777M, G778_Y779insGSP, P780_Y781insGSP (i.e.,G778_P780dup), L786V, N813D, R840W, V842I, T862A, R896G, E1021Q or approved by the KOSMOS Molecular Tumor Board
Otros nombres:
BRAF_V600E/D/K/R mutations
Otros nombres:
FH inactivating mutations or approved by the KOSMOS Molecular Tumor Board
Otros nombres:
ROS1 gene fusion using either a fluo rescence in situ hybridization (FISH) or next-generation sequencing (NGS) or approved by the KOSMOS Molecular Tumor Board
Otros nombres:
RET fusion or mutations; CCDC6 RET, RET V804L, RET V804M, RET M918T, KIF5B-RET, RET C634W or approved by the KOSMOS Molecular Tumor Board
Otros nombres:
|
|
Tier 2: Alternative treatments
If there are no KOSMOS-II drugs (Tier 1) or clinical trials (Tier 3) appropriate for patients, the MTB may recommend alternative treatment options (e.g., conventional therapy, radiotherapy, or supportive care). |
|
|
Tier 3: Clinical trial
If patient is eligible for clinical trials matched for actionable genomic alterations found in NGS testing, the MTB will recommend enrollment to clinical trials. |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
To evaluate the feasibility of molecular profiling guided therapies (MGT) based on genomic alterations in patients with advanced solid tumors in terms of the proportion of receipt of the treatment
Periodo de tiempo: 12 months after treatment initiation (estimated average)
|
Percentage of patients who receive molecular profiling guided therapy as recommended by MTB, either in therapeutic use of investigational products (KOSMOS-II drugs), alternative treatment, or clinical trial. |
12 months after treatment initiation (estimated average)
|
|
To evaluate the effectiveness of molecular profiling guided therapies in terms of clinical benefit rate (CR/PR/SD beyond 16 +/- 2 weeks) in Tier 1* population
Periodo de tiempo: Assessed at 16 weeks of treatment
|
Percentage of patients achieving response defined as CR/PR/SD at 16 ± 2 weeks reported by site physician |
Assessed at 16 weeks of treatment
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Objective response rate
Periodo de tiempo: 12 months after treatment initiation (estimated average)
|
The proportion of patients who obtained CR/PR as the best response according to the RECIST 1.1 criteria |
12 months after treatment initiation (estimated average)
|
|
Progression-free survival
Periodo de tiempo: 12 months after treatment initiation (estimated average)
|
Progression-free survival in accordance with local clinical practice |
12 months after treatment initiation (estimated average)
|
|
Treatment duration
Periodo de tiempo: 12 months after treatment initiation (estimated average)
|
The period from the start of treatment to the end of treatment for any reason |
12 months after treatment initiation (estimated average)
|
|
1-year overall survival rate
Periodo de tiempo: 12 months after treatment initiation (estimated average)
|
Proportion of patients alive 1 year after study registration |
12 months after treatment initiation (estimated average)
|
|
To evaluate safety of molecular profiling guided therapies
Periodo de tiempo: 12 months after treatment initiation (estimated average)
|
The incidence of serious adverse events will be calculated among the adverse events in patients with Tier 1 and Tier 3. ( based on NCI-CTCAE v5.0 ) |
12 months after treatment initiation (estimated average)
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Director de estudio: JEEHYUN KIM, Seoul National University Bundang Hospital
Publicaciones y enlaces útiles
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
- Procesos Patológicos
- Neoplasias
- Procesos Neoplásicos
- Condiciones Patológicas, Signos y Síntomas
- Metástasis de neoplasias
- Aminoácidos, péptidos y proteínas
- Proteínas
- Compuestos de azufre
- Químicos orgánicos
- Compuestos heterocíclicos
- Compuestos heterocíclicos, 2 anillos
- Compuestos heterocíclicos, anillo fusionado
- Compuestos policíclicos
- Amidas
- Indoles
- Anticuerpos, monoclonales, humanizados
- Anticuerpos, monoclonal
- Anticuerpos
- Inmunoglobulinas
- Inmunoproteínas
- Proteínas de la sangre
- Globulinas séricas
- Globulinas
- Macrólidos
- Lactonas
- Lactamas, macrocíclicas
- Compuestos macrocíclicos
- Sulfonamidas
- Sulfonas
- Quinazolina
- Maytansine
- Trastuzumab
- Clorhidrato de erlotinib
- Bevacizumab
- Ado-Trastuzumab Emtansina
- Vemurafenib
- pertuzumab
- atezolizumab
- entretinib
- alectinib
- pralsetinib
Otros números de identificación del estudio
- KCSG AL 22-09
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .