Phase II Umbrella Study Directed by Next Generation Sequencing

NCT03574402 | Unknown Phase 2

• 1 other identifier: CTONG1702
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II, umbrella trial study directed by next generation sequencing (NGS) works in Chinese patients with advanced stage NSCLC who never received any anti-tumor treatment. The purpose of this study is to evaluate efficacy of targeted therapies or immunotherapy to NSCLC patients whose tumor harbors a genomic variant known to be a drug target or to predict sensitivity to a drug.

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

NSCLC; advanced stage; high throughput sequencing; targeted therapy; immunotherapy

Outcome Measures

Primary Outcomes (1)

• Response rate (RR)

  RECIST version 1.1

  24 months

Secondary Outcomes (7)

• Progression-free survival (PFS)

  24 months

• Overall survival (OS)

  48 months

• Disease control rate（DCR）

  24 months

• Duration of response (DOR)

  24 months

• Toxicity (number of patients with treatment-related AE as assessed by CTCAE v4.03)

  24 months

Study Arms (18)

Arm1: Avitinib Maleate

EXPERIMENTAL

Patients with EGFR de novo T790m mutation receive Avitinib 300mg orally (PO) twice daily (BID) on day 1-28.

Drug: Avitinib Maleate

Arm2: Chidamide plus Afatinib

EXPERIMENTAL

Patients with EGFR sensitive mutation with BIM deletion polymorphism receive Afatinib plus Chidamide. Chidamide will be administered 30mg orally twice weekly, 28 days as one cycle. Afatinib will be administered 40mg orally once a day, 28 days as one cycle.

Drug: Afatinib; Drug: Chidamide

Arm3: crizotinib

EXPERIMENTAL

Patients with MET 14 exon mutation receive crizotinib 250mg PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Crizotinib

Arm4: X396

EXPERIMENTAL

Patients with MET amplification receive X396 225mg PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: X-396

Arm5: X396

EXPERIMENTAL

Patients with ROS1 fusion receive X396 225mg PO QD on days 1-28. 28 days as one cycle. Courses repeat every 2 cycles in the absence of disease progression or unacceptable toxicity.

Drug: X-396

Arm6: X396

EXPERIMENTAL

Patients with Ntrk1/2/3 fusion receive X396 225mg PO QD on days 1-28. 28 days as one cycle. Courses repeat every 2 cycles in the absence of disease progression or unacceptable toxicity.

Drug: X-396

Arm7: Pyrotinib Maleate

EXPERIMENTAL

Patients with HER2 mutation receive Pyrotinib Maleate 400mg PO QD on days 1-28. 28 days as one cycle. Courses repeat every 2 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Pyrotinib Maleate

Arm8: AZD3759

EXPERIMENTAL

EGFR sensitive mutation with brain/meningeal metastasis receive AZD3759 200mg PO BID on days 1-28. 28 days as one cycle. Courses repeat every 2 cycles in the absence of disease progression or unacceptable toxicity.

Drug: AZD3759

Arm9: Pirotinib

EXPERIMENTAL

Patients with EGFR20ins mutation positive receive Pirotinib. This arm was divided into three groups: Group 1, 60mg PO QD on days 1-28. 28 days as one cycle. Group 2, 40mg PO BID on days 1-28. 28 days as one cycle. Group 3, Dosage was determined according to the number of PR patients in Group 2.

Drug: Pirotinib

Arm10: Nimotuzumab plus gemcitabine and carboplatin

EXPERIMENTAL

Lung squamous cell carcinoma with EGFR amplification. Nimotuzumab 400mg, iv gtt. on day 1,8,15. Gemcitabine 1250mg/m\^2, iv gtt. on day 1,8. Carboplatin AUC5, iv gtt. Q3W on day 1. 21 days as one cycle. Courses repeat every 2 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Nimotuzumab; Drug: Gemcitabine; Drug: Carboplatin

Arm11: Nimotuzumab plus pemetrexed and cisplatin

EXPERIMENTAL

Lung adenocarcinoma with EGFR amplification. Nimotuzumab 400mg, iv gtt. on day 1,8,15. pemetrexed 500mg/m\^2, iv gtt. on day 1. Cisplatin 75mg/m\^2, iv gtt. Q3W on day 1. 21 days as one cycle. Courses repeat every 2 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Nimotuzumab; Drug: Pemetrexed; Drug: Cisplatin

Arm12: Pirotinib

EXPERIMENTAL

Patients with rare EGFR mutation receive Pirotinib. This arm was divided into two groups: Group 1, 40mg PO BID on days 1-28. 28 days as one cycle. Group 2, Dosage was determined according to the number of PR patients in Group 1.

Drug: Pirotinib

Arm13: Avitinib

EXPERIMENTAL

Patients with EGFR sensitive mutation receive Avitinib 300mg PO BID on days 1-28. 28 days as one cycle. Courses repeat every 2 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Avitinib Maleate

Arm14: Sintilimab

EXPERIMENTAL

Patients with PD-L1(TPS)≥50% without EGFR mutation or ALK rearrangement. Sintilimab 200mg iv gtt. Q3W on day1. 21 days as one cycle. Courses repeat every 2 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Sintilimab

Arm15: Sintilimab

EXPERIMENTAL

Patients with TMB≥10 mut/Mb，1%≦PD-L1\<50% without EGFR mutation or ALK rearrangement. Sintilimab 200mg iv gtt. Q3W on day1. 21 days as one cycle. Courses repeat every 2 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Sintilimab

Arm16: Sintilimab

EXPERIMENTAL

Patients with KRAS and TP53 mutation, 1%≦PD-L1\<50%, TMB\<10 mut/Mb without EGFR mutation or ALK rearrangement. Sintilimab 200mg iv gtt. Q3W on day1. 21 days as one cycle. Courses repeat every 2 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Sintilimab

Arm17: Sintilimab plus pemetrexed and cisplatin

EXPERIMENTAL

Patients with PD-L1\<1%, TMB\<10 mut/mb without EGFR mutation, ALK rearrangement, KRAS or TP53 mutation. Sintilimab 200mg iv gtt. Q3W on day1. Pemetrexedb 500mg/m\^2 iv gtt. Q3W on day1. Cisplatin 75mg/m\^2 iv gtt. Q3W on day1. 21 days as one cycle. Courses repeat every 2 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Pemetrexed; Drug: Cisplatin; Drug: Sintilimab

Arm18: Sintilimab plus Gemcitabine and carboplatin

EXPERIMENTAL

Patients with PD-L1\<1%, TMB\<10 mut/mb without EGFR mutation, ALK rearrangement, KRAS or TP53 mutation. Sintilimab 200mg iv gtt. Q3W on day1. Gemcitabine 1g/m\^2 iv gtt. on day1,8. Carboplatin AUC5 iv gtt. Q3W on day1. 21 days as one cycle. Courses repeat every 2 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Sintilimab; Drug: Gemcitabine; Drug: Carboplatin

Interventions

Avitinib Maleate DRUG

300mg orally (PO) twice daily (BID) on day 1-28.

Also known as: AC0010

Arm13: Avitinib; Arm1: Avitinib Maleate

Afatinib DRUG

40mg orally once a day, 28 days as one cycle.

Also known as: Giotrif

Arm2: Chidamide plus Afatinib

Crizotinib DRUG

250mg PO QD on days 1-28. 28 days as one cycle.

Also known as: Xalkori

Arm3: crizotinib

X-396 DRUG

225mg PO QD on days 1-28. 28 days as one cycle.

Also known as: ensartinib

Arm4: X396; Arm5: X396; Arm6: X396

Chidamide DRUG

30mg orally twice weekly, 28 days as one cycle.

Also known as: Epidaza

Arm2: Chidamide plus Afatinib

Pyrotinib Maleate DRUG

400mg PO QD on days 1-28. 28 days as one cycle.

Also known as: SHR1258

Arm7: Pyrotinib Maleate

AZD3759 DRUG

200mg PO BID on days 1-28. 28 days as one cycle.

Arm8: AZD3759

Pirotinib DRUG

60mg PO QD/40mg PO BID on days 1-28. 28 days as one cycle.

Also known as: KBP-5209

Arm12: Pirotinib; Arm9: Pirotinib

Nimotuzumab DRUG

400mg, iv gtt. on day 1,8,15. 21 days as one cycle.

Arm10: Nimotuzumab plus gemcitabine and carboplatin; Arm11: Nimotuzumab plus pemetrexed and cisplatin

Pemetrexed DRUG

500mg/m\^2, iv gtt. Q3W. 21 days as one cycle.

Also known as: LY231514

Arm11: Nimotuzumab plus pemetrexed and cisplatin; Arm17: Sintilimab plus pemetrexed and cisplatin

Cisplatin DRUG

75mg/m\^2, iv gtt. Q3W on day1. 21 days as one cycle.

Also known as: CDDP

Arm11: Nimotuzumab plus pemetrexed and cisplatin; Arm17: Sintilimab plus pemetrexed and cisplatin

Sintilimab DRUG

200mg iv gtt. Q3W on day1. 21 days as one cycle.

Arm14: Sintilimab; Arm15: Sintilimab; Arm16: Sintilimab; Arm17: Sintilimab plus pemetrexed and cisplatin; Arm18: Sintilimab plus Gemcitabine and carboplatin

Gemcitabine DRUG

1g/m\^2 iv gtt. on day1,8. 21 days as one cycle.

Also known as: LY188011

Arm18: Sintilimab plus Gemcitabine and carboplatin

Carboplatin DRUG

AUC5 iv gtt. Q3W on day1. 21 days as one cycle.

Also known as: NSC 241240

Arm10: Nimotuzumab plus gemcitabine and carboplatin; Arm18: Sintilimab plus Gemcitabine and carboplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed, unresectable stage IIIB or stage IV NSCLC
• Patients who have never received any anticancer treatment regimen Note: Patients that have received adjuvant or neoadjuvant chemotherapy and developed metastatic disease after 12 months from the end of that therapy would be eligible for enrollment.
• Measurable disease according to RECIST v.1.1 (Irradiated lesions are not considered measurable unless they have clearly progressed since radiotherapy)
• With or without brain or leptomeningeal metastasis (BM/LM). For patients with symptoms of BM/LM, no need for local therapy should be confirmed by investigator and no dramatic decline of performance status in 2 weeks.
• ECOG performance status ≤ 2
• Expected survival \> 12 weeks
• Patients must be suitable and willing to undergo mandatory tumor biopsy according to treating institution's guidelines and requirements for such procedure if there is no archival biopsy available.
• Provision of signed and dated written informed consent by the patient or legally acceptable representative prior to any study-specific procedures.
• Palliative radiotherapy was allowed before enrollment, and radiotherapy-related toxicity grade should no more than 1 (ctcae4.03).
• No anti-tumor Chinese medicine has been used in the past, or has been used for no more than 3 doses, and stopped for more than 2 weeks before enrollment.
• Absolute neutrophil count (ANC) ≥ 1.5x10\^9/L without the use of growth factor in the past 14 days. Platelets ≥ 90 × 10\^9/L without blood transfusion in the past 14 days. Hemoglobin \> 9g/dL.
• Negative pregnancy test (only for women with pregnancy possibility). No possibility of pregnancy defined as at least one year after menopause, or having undergone surgical sterilization or hysterectomy. All patients (male or female) agreed to take contraceptive measures during the treatment and within 8 weeks after the treatment.

You may not qualify if:

• Active hepatitis (HBsAg positive and HBV copy number in upper limit of normal)
• Previous or current active interstitial lung disease (ILD)
• Patients known to be HIV positive or with other acquired, congenital immunodeficiency diseases, or with a medical history of organ transplantation.
• Major surgery ≤ 2 weeks prior to study entry.
• Any other malignancies within the last 5 years before study enrollment, except for un completely resected basal cell carcinoma, in situ bladder cancer, cervical carcinoma in situ.
• Patients previously treated with the investigational drugs or known to be allergic to ingredients or excipients of the investigational drugs.
• Pregnant or lactating women.
• Patients with swallowing dysfunction, active gastrointestinal disease or other diseases that significantly affect the absorption, distribution, metabolism and excretion of oral drugs. The patients who have had subtotal gastrectomy before. (this standard is applicable to the arms with oral drugs only)
• Body temperature above 38 ℃ in the past week, or there was active infection with clinical significance. Active tuberculosis;
• Evidence of serious or uncontrollable systemic diseases (such as severe mental, neurological, epilepsy or dementia, unstable or uncompensated respiratory, cardiovascular, liver or kidney diseases, uncontrolled hypertension \[higher than CTCAE Level 3 hypertension after drug treatment\]);
• Patients with bleeding tendency or taking anticoagulants ;
• There are significant clinical abnormalities in rhythm, conduction or morphology of resting ECG, such as complete left bundle branch block, heart block above degree II, clinically significant ventricular arrhythmia or atrial fibrillation, unstable angina, congestive heart failure, chronic heart failure with NYHA grade ≥ 2.
• Myocardial infarction, coronary / peripheral artery bypass or cerebrovascular accident occurred within 3 months.
• QTc of 12 lead ECG was ≥ 450 ms in male and ≥ 470 ms in female;
• Diagnosed with another malignant disease in the past five years besides NSCLC.

Sponsors & Collaborators

• Guangdong Association of Clinical Trials: lead
• Chinese Thoracic Oncology Group: collaborator

Study Sites (1)

Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology

Guangzhou, Guangdong, 510080, China

RECRUITING

Related Publications (2)

• Liu SM, Tu HY, Wei XW, Yan HH, Dong XR, Cui JW, Zhou Z, Xu CR, Zheng MY, Li YS, Wang Z, Bai XY, Li AN, Sun YL, Huang J, Lin JX, Ke EE, Xu BF, Lu C, Du Y, Chen Y, Ma R, Wang BH, Cang SD, Wang BC, Chen HJ, Yang JJ, Li Y, Zhou Q, Wu YL. First-line pyrotinib in advanced HER2-mutant non-small-cell lung cancer: a patient-centric phase 2 trial. Nat Med. 2023 Aug;29(8):2079-2086. doi: 10.1038/s41591-023-02461-x. Epub 2023 Jul 24.

  PMID: 37488286 DERIVED

• Liu SM, Yan HH, Wei XW, Lu C, Dong XR, Du Y, Cui JW, Chen Y, Ma R, Wang BH, Zhou Z, Cang SD, Yang JJ, Tu HY, Zhang XC, Zhong WZ, Zhou Q, Wu YL. Biomarker-Driven Studies With Multi-targets and Multi-drugs by Next-Generation Sequencing for Patients With Non-Small-Cell Lung Cancer: An Open-Label, Multi-center, Phase II Adaptive Umbrella Trial and a Real-World Observational Study (CTONG1702&CTONG1705). Clin Lung Cancer. 2022 Nov;23(7):e395-e399. doi: 10.1016/j.cllc.2022.05.009. Epub 2022 May 11.

  PMID: 35659479 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

abivertinib; Afatinib; Crizotinib; ensartinib; N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide; AZD3759; nimotuzumab; Pemetrexed; Cisplatin; sintilimab; Gemcitabine; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Piperidines; Heterocyclic Compounds, 1-Ring; Aminopyridines; Pyridines; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Coordination Complexes

Study Officials

• Yi-Long Wu

  Guangdong Association of Clinical Trials

  STUDY CHAIR

Central Study Contacts

Yi-Long Wu, Professor

CONTACT

862083827812; syylwu@live.cn

Qing Zhou, Dr.

CONTACT

+8613544561166; gzzhouqing@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2018
• First Posted: July 2, 2018
• Study Start: July 9, 2018
• Primary Completion: December 30, 2022
• Study Completion: December 30, 2024
• Last Updated: December 6, 2022

Record last verified: 2022-12

Locations

CN (1)