Clinical trial NCT03838588: The Tracking Molecular Evolution for NSCLC (T-MENC) Study
Official title: Tracking Genomic Cancer Evolution in Patients for Stage IB,II and IIIA Non-small Cell Lung Cancer After Radical Resection: The Tracking Molecular Evolution for NSCLC (T-MENC) Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Lung Neoplasms
Lung Cancer
Nonsmall Cell Lung Cancer
Adenocarcinoma of Lung
Lead sponsor: Geneplus-Beijing Co. Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Xuanwu Hospital, Beijing
First posted: 2019-02-12
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Tracking Genomic Cancer Evolution in Patients for Stage IB,II and IIIA Non-small Cell Lung Cancer After Radical Resection.

Brief summary: Tumor genomic clonal evolution assessed with liquid biopsy of stage IB,II and IIIA non-small cell lung cancer patients after getting radical resection. Plasma circulating tumor DNA (ctDNA) analysis detects molecule residual disease and predicts recurrence in patients. The concordance of the relative abundance of mutations in plasma ctDNA with cancer recurrence.

Detailed description: In the study, 200 of stage IB,II and IIIA non-small cell lung cancer patients obtained radical resection will be recruited. All the patients will receive biopsy genotype assay and ctDNA liquid biopsy. The abundance of mutations of ctDNA was tracked at 4 time points, including:

1. st: 10 Days after patients received radical resection.
2. nd: When patients finished the chemotherapy or target drug delivery two cycles.
3. rd: 10 Days after patients finished the chemotherapy or target drug delivery four cycles.
4. th: When tumor recrudescence / 2 years after radical resection.

Tumor genomic clonal evolution was assessed by analyzing the relative abundance of mutations in plasma circulating tumor DNA (ctDNA).

Eligibility criteria: Inclusion Criteria:

1. Provision of informed consent and assigned.
2. Newly diagnosed and histological or cytological confirmed stage IB-IIIA lung adenocarcinoma or non-smoking squamous cell carcinoma patients according to the AJCC staging system.
3. Expected radical resection.
4. Patients expected more than 3 months of survival time.
5. Willingness to comply with required protocols and give permission to use the data for clinical research and products development.

Exclusion Criteria:

1. Patients who want Neo-adjuvant therapy.
2. Patients with T3-4N1 Pancoast tumors (superior sulcal tumors).
3. Multi-station N2 non-small cell lung cancer with lymph node metastasis.
4. Eastern cooperative oncology group (ECOG) performance status \> 2 after postoperative chemotherapy
5. Eastern cooperative oncology group (ECOG) performance status \> 4 after postoperative targeted therapy.
6. Patients must never ever has received for any history of radiotherapy/ chemotherapy/surgery before.
7. Patients have other primary cancers.
8. Known central nervous system metastasis.
9. Patients expected less than 3 months of survival time.
10. Other situations mismatch this program.

Primary outcomes:
measure: Tumor genomic clonal evolution assessed with liquid biopsy of stage IB,II and IIIA non-small cell lung cancer patients after getting radical resection.
timeFrame: From assignment of the first subject to the time point when tumor recrudescence or 2 years after radical resection. The last participant will be recruited before June 30,2021.
measure: The concordance of the plasma ctDNA detection status with Progress Free Survival (PFS) and Overall Survival (OS) after radical resection or/and under adjuvant therapy.
timeFrame: From assignment of the first subject to the time point when tumor recrudescence or 2 years after radical resection. The last participant will be recruited before June 30, 2021.
Secondary outcomes:
measure: Evaluation of ctDNA detecting assay in monitoring recurrence of early stage of lung cancer after radical resection.
timeFrame: From assignment of the first subject to the time point when tumor recrudescence or 2 years after radical resection. The last participant will be recruited before June 30, 2021.
measure: The molecular mechanism between the tumor recurrence and ctDNA mutations
timeFrame: From assignment of the first subject to the time point when tumor recrudescence or 2 years after radical resection. The last participant will be recruited before June 30, 2021.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Hospital
state: Beijing
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: China-Japan Friendship Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Xuanwu Hospital Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Beijing Chest Hospital, Capital Medical University
state: Beijing
city: Shijiazhuang
country: China
facility: Fourth Hospital of Hebei Medical University
state: Hebei
city: Shijiazhuang
country: China
facility: Hebei General Hospital
state: Hebei
city: Tangshan
country: China
facility: Tangshan People's Hospital
state: Hebei
city: Changchun
country: China
facility: The First Bethune Hospital of Jilin University
state: Jilin
Study officials:
affiliation: Xuanwu Hospital, Beijing
name: Yi Zhang, MD
role: STUDY_CHAIR
affiliation: Beijing Hospital
name: Yao guang Sun, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China +86-139 1189 2587 lijie821cn@163.com
name: Jie Li, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The First Hospital of Jilin University
name: Hong Zhang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Tangshan People's Hospital
name: Zhi qiang Wang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijing Chest Hospital, Capital Medical University
name: Ming He, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijing Chest Hospital, Capital Medical University
name: Zi dan Wang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hebei General Hospital
name: Li jun Liu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
name: Kang Shao, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: China-Japan Friendship Hospital
name: Chao yang Liang
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bettegowda C, Sausen M, Leary RJ, Kinde I, Wang Y, Agrawal N, Bartlett BR, Wang H, Luber B, Alani RM, Antonarakis ES, Azad NS, Bardelli A, Brem H, Cameron JL, Lee CC, Fecher LA, Gallia GL, Gibbs P, Le D, Giuntoli RL, Goggins M, Hogarty MD, Holdhoff M, Hong SM, Jiao Y, Juhl HH, Kim JJ, Siravegna G, Laheru DA, Lauricella C, Lim M, Lipson EJ, Marie SK, Netto GJ, Oliner KS, Olivi A, Olsson L, Riggins GJ, Sartore-Bianchi A, Schmidt K, Shih lM, Oba-Shinjo SM, Siena S, Theodorescu D, Tie J, Harkins TT, Veronese S, Wang TL, Weingart JD, Wolfgang CL, Wood LD, Xing D, Hruban RH, Wu J, Allen PJ, Schmidt CM, Choti MA, Velculescu VE, Kinzler KW, Vogelstein B, Papadopoulos N, Diaz LA Jr. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med. 2014 Feb 19;6(224):224ra24. doi: 10.1126/scitranslmed.3007094.
citation: Tie J, Wang Y, Tomasetti C, Li L, Springer S, Kinde I, Silliman N, Tacey M, Wong HL, Christie M, Kosmider S, Skinner I, Wong R, Steel M, Tran B, Desai J, Jones I, Haydon A, Hayes T, Price TJ, Strausberg RL, Diaz LA Jr, Papadopoulos N, Kinzler KW, Vogelstein B, Gibbs P. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer. Sci Transl Med. 2016 Jul 6;8(346):346ra92. doi: 10.1126/scitranslmed.aaf6219.
citation: Abbosh C, Birkbak NJ, Wilson GA, Jamal-Hanjani M, Constantin T, Salari R, Le Quesne J, Moore DA, Veeriah S, Rosenthal R, Marafioti T, Kirkizlar E, Watkins TBK, McGranahan N, Ward S, Martinson L, Riley J, Fraioli F, Al Bakir M, Gronroos E, Zambrana F, Endozo R, Bi WL, Fennessy FM, Sponer N, Johnson D, Laycock J, Shafi S, Czyzewska-Khan J, Rowan A, Chambers T, Matthews N, Turajlic S, Hiley C, Lee SM, Forster MD, Ahmad T, Falzon M, Borg E, Lawrence D, Hayward M, Kolvekar S, Panagiotopoulos N, Janes SM, Thakrar R, Ahmed A, Blackhall F, Summers Y, Hafez D, Naik A, Ganguly A, Kareht S, Shah R, Joseph L, Marie Quinn A, Crosbie PA, Naidu B, Middleton G, Langman G, Trotter S, Nicolson M, Remmen H, Kerr K, Chetty M, Gomersall L, Fennell DA, Nakas A, Rathinam S, Anand G, Khan S, Russell P, Ezhil V, Ismail B, Irvin-Sellers M, Prakash V, Lester JF, Kornaszewska M, Attanoos R, Adams H, Davies H, Oukrif D, Akarca AU, Hartley JA, Lowe HL, Lock S, Iles N, Bell H, Ngai Y, Elgar G, Szallasi Z, Schwarz RF, Herrero J, Stewart A, Quezada SA, Peggs KS, Van Loo P, Dive C, Lin CJ, Rabinowitz M, Aerts HJWL, Hackshaw A, Shaw JA, Zimmermann BG; TRACERx consortium; PEACE consortium; Swanton C. Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution. Nature. 2017 Apr 26;545(7655):446-451. doi: 10.1038/nature22364.
citation: Chaudhuri AA, Chabon JJ, Lovejoy AF, Newman AM, Stehr H, Azad TD, Khodadoust MS, Esfahani MS, Liu CL, Zhou L, Scherer F, Kurtz DM, Say C, Carter JN, Merriott DJ, Dudley JC, Binkley MS, Modlin L, Padda SK, Gensheimer MF, West RB, Shrager JB, Neal JW, Wakelee HA, Loo BW Jr, Alizadeh AA, Diehn M. Early Detection of Molecular Residual Disease in Localized Lung Cancer by Circulating Tumor DNA Profiling. Cancer Discov. 2017 Dec;7(12):1394-1403. doi: 10.1158/2159-8290.CD-17-0716. Epub 2017 Sep 24.