Clinical trial NCT05525858: KPMNG Study of MOlecular Profiling Guided Therapy Based on Genomic Alterations in Advanced Solid Tumors II
Official title: KOrean Precision Medicine Networking Group Study of MOlecular Profiling Guided Therapy Based on Genomic Alterations in Advanced Solid Tumors II
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Solid Tumor
Advanced Solid Tumor
Metastatic Cancer
Lead sponsor: Seoul National University Bundang Hospital
Sponsor class: OTHER
Collaborators: name: Korean Cancer Study Group
name: Roche Pharma AG
First posted: 2022-09-02
Enrollment: 1000
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 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

Brief summary: 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)

Detailed description: 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

Eligibility criteria: 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.

  1. 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.
  2. 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

Primary outcomes:
measure: 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
timeFrame: 12 months after treatment initiation (estimated average)
measure: 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
timeFrame: Assessed at 16 weeks of treatment
Secondary outcomes:
measure: Objective response rate
timeFrame: 12 months after treatment initiation (estimated average)
measure: Progression-free survival
timeFrame: 12 months after treatment initiation (estimated average)
measure: Treatment duration
timeFrame: 12 months after treatment initiation (estimated average)
measure: 1-year overall survival rate
timeFrame: 12 months after treatment initiation (estimated average)
measure: To evaluate safety of molecular profiling guided therapies
timeFrame: 12 months after treatment initiation (estimated average)
Other outcomes:
Locations:
city: Bucheon
country: Korea, Republic of
facility: Soonchunhyang University Hospital Bucheon
city: Chungju
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Hospital
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Chilgok Hospital
city: Daegu
country: Korea, Republic of
facility: Yeungnam University Medical Center
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital
city: Goyang
country: Korea, Republic of
facility: National Cancer Center
city: Hwasun
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Incheon
country: Korea, Republic of
facility: The Catholic University of Korea, Incheon St. Mary's Hospital
city: Jeonju
country: Korea, Republic of
facility: Jeonbuk National University Hospital
city: Jinju
country: Korea, Republic of
facility: Gyeongsang National University Hospital
city: Pusan
country: Korea, Republic of
facility: Dong-A University Hospital
city: Seongnam
country: Korea, Republic of
facility: Cha University Bundang Medical Center
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Chung-ang University Hospital
city: Seoul
country: Korea, Republic of
facility: Ewha womans university Mokdong Hospital
city: Seoul
country: Korea, Republic of
facility: Gangbuk Samsung Hospital
city: Seoul
country: Korea, Republic of
facility: Hanyang University Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul ST. Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Yeouido St. Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Yonsei Cancer Hospital
city: Suwon
country: Korea, Republic of
facility: Ajou University Hospital
city: Suwon
country: Korea, Republic of
facility: The Catholic University of Korea, ST. Vincent's Hospital
city: Ulsan
country: Korea, Republic of
facility: Ulsan University Hospital
city: Wŏnju
country: Korea, Republic of
facility: Wonju Severance Christian Hospital
city: Yangsan
country: Korea, Republic of
facility: Pusan National University Yangsan Hospital
Study officials:
affiliation: Seoul National University Bundang Hospital
name: JEEHYUN KIM
role: STUDY_DIRECTOR
References: