Clinical Trials /

Phase II Umbrella Study Directed by Next Generation Sequencing

NCT03574402

Description:

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.

Related Conditions:
  • Lung Adenocarcinoma
  • Non-Small Cell Lung Carcinoma
  • Squamous Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase II Umbrella Study Directed by Next Generation Sequencing
  • Official Title: An Open-label, Multi-center, Phase II Umbrella Study to Assess Efficacy of Targeted Therapy or Immunotherapy Directed by Next Generation Sequencing (NGS) in Chinese Patients With Advanced NSCLC (TRUMP)

Clinical Trial IDs

  • ORG STUDY ID: CTONG1702
  • NCT ID: NCT03574402

Conditions

  • Carcinoma, Non-Small-Cell Lung

Interventions

DrugSynonymsArms
Avitinib MaleateAC0010Arm13: Avitinib
AfatinibGiotrifArm2: Chidamide plus Afatinib
CrizotinibXalkoriArm3: crizotinib
X-396ensartinibArm4: X396
ChidamideEpidazaArm2: Chidamide plus Afatinib
Pyrotinib MaleateSHR1258Arm7: Pyrotinib Maleate
AZD3759Arm8: AZD3759
PirotinibKBP-5209Arm12: Pirotinib
NimotuzumabArm10: Nimotuzumab plus gemcitabine and carboplatin
PemetrexedLY231514Arm11: Nimotuzumab plus pemetrexed and cisplatin
CisplatinCDDPArm11: Nimotuzumab plus pemetrexed and cisplatin
SintilimabArm14: Sintilimab
GemcitabineLY188011Arm18: Sintilimab plus Gemcitabine and carboplatin
GemcitabineLY188011Arm10: Nimotuzumab plus gemcitabine and carboplatin
CarboplatinNSC 241240Arm10: Nimotuzumab plus gemcitabine and carboplatin

Purpose

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.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To evaluate the anti-tumor efficacy of targeted agents or checkpiont inhibitors in
      advanced stage NSCLC with genomic alteration.

      SECONDARY OBJECTIVES:

      I. To evaluate the clinical efficacy of targeted agents or checkpiont inhibitors in advanced
      stage NSCLC with genomic alteration.

      II. To evaluate safty and tolerence of targeted agents or checkpiont inhibitors in advanced
      stage NSCLC with genomic alteration.
    

Trial Arms

NameTypeDescriptionInterventions
Arm1: Avitinib MaleateExperimentalPatients with EGFR de novo T790m mutation receive Avitinib 300mg orally (PO) twice daily (BID) on day 1-28.
  • Avitinib Maleate
Arm2: Chidamide plus AfatinibExperimentalPatients 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.
  • Afatinib
  • Chidamide
Arm3: crizotinibExperimentalPatients 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.
  • Crizotinib
Arm4: X396ExperimentalPatients 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.
  • X-396
Arm5: X396ExperimentalPatients 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.
  • X-396
Arm6: X396ExperimentalPatients 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.
  • X-396
Arm7: Pyrotinib MaleateExperimentalPatients 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.
  • Pyrotinib Maleate
Arm8: AZD3759ExperimentalEGFR 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.
  • AZD3759
Arm9: PirotinibExperimentalPatients 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.
  • Pirotinib
Arm10: Nimotuzumab plus gemcitabine and carboplatinExperimentalLung 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.
  • Nimotuzumab
  • Gemcitabine
  • Carboplatin
Arm11: Nimotuzumab plus pemetrexed and cisplatinExperimentalLung 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.
  • Nimotuzumab
  • Pemetrexed
  • Cisplatin
Arm12: PirotinibExperimentalPatients 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.
  • Pirotinib
Arm13: AvitinibExperimentalPatients 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.
  • Avitinib Maleate
Arm14: SintilimabExperimentalPatients 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.
  • Sintilimab
Arm15: SintilimabExperimentalPatients 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.
  • Sintilimab
Arm16: SintilimabExperimentalPatients 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.
  • Sintilimab
Arm17: Sintilimab plus pemetrexed and cisplatinExperimentalPatients 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.
  • Pemetrexed
  • Cisplatin
  • Sintilimab
Arm18: Sintilimab plus Gemcitabine and carboplatinExperimentalPatients 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.
  • Sintilimab
  • Gemcitabine
  • Carboplatin

Eligibility Criteria

        Inclusion Criteria:

          1. Histologically or cytologically confirmed, unresectable stage IIIB or stage IV NSCLC

          2. 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.

          3. Measurable disease according to RECIST v.1.1 (Irradiated lesions are not considered
             measurable unless they have clearly progressed since radiotherapy)

          4. 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.

          5. ECOG performance status ≤ 2

          6. Expected survival > 12 weeks

          7. 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.

          8. Provision of signed and dated written informed consent by the patient or legally
             acceptable representative prior to any study-specific procedures.

          9. Palliative radiotherapy was allowed before enrollment, and radiotherapy-related
             toxicity grade should no more than 1 (ctcae4.03).

         10. 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.

         11. 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.

         12. 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.

        Exclusion Criteria:

          1. Active hepatitis (HBsAg positive and HBV copy number in upper limit of normal)

          2. Previous or current active interstitial lung disease (ILD)

          3. Patients known to be HIV positive or with other acquired, congenital immunodeficiency
             diseases, or with a medical history of organ transplantation.

          4. Major surgery ≤ 2 weeks prior to study entry.

          5. 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.

          6. Patients previously treated with the investigational drugs or known to be allergic to
             ingredients or excipients of the investigational drugs.

          7. Pregnant or lactating women.

          8. 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)

          9. Body temperature above 38 ℃ in the past week, or there was active infection with
             clinical significance. Active tuberculosis;

         10. 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]);

         11. Patients with bleeding tendency or taking anticoagulants ;

         12. 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.

         13. Myocardial infarction, coronary / peripheral artery bypass or cerebrovascular accident
             occurred within 3 months.

         14. QTc of 12 lead ECG was ≥ 450 ms in male and ≥ 470 ms in female;

         15. Diagnosed with another malignant disease in the past five years besides NSCLC.

         16. More than 30% of the bone marrow had received radiotherapy within 4 weeks before
             treatment.

         17. Any drugs known to extend QT interval were being used within 2 weeks prior to first
             administration.

         18. Strong CYP3A4 inhibitor/inductionor or CYP3A4 substrate were used within 2 weeks,
             including but not limited to azanavir, clarithromycin, inddenavir, itraconazole,
             ketoconazole, nefazodone, nefinavir, ritonavir, xaquinavir, talicamycin, acesodamycin,
             voriconazole, carbamazepine, phenobarbital, phenytoin, rifampin, rifampin, Hypericum
             perforatum, dihydroergotamine, ergotamine, pimozite, astemizole, cisapride and
             terfenadine.

         19. Strong P-gp inhibitor was used within 2 weeks (including but not limited to verapamil,
             cyclosporine A and right verapamil).

         20. Other potential risks that are not suitable for the study.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Response rate (RR)
Time Frame:24 months
Safety Issue:
Description:RECIST version 1.1

Secondary Outcome Measures

Measure:Progression-free survival (PFS)
Time Frame:24 months
Safety Issue:
Description:RECIST version 1.1
Measure:Overall survival (OS)
Time Frame:48 months
Safety Issue:
Description:Overall Survival is defined as the time from first dose to death due to any cause. Through the follow-up within 30 days after study completion or termination of the last subject, death and date of death will be checked for subject alive during treatment period
Measure:Disease control rate(DCR)
Time Frame:24 months
Safety Issue:
Description:RECIST version 1.1
Measure:Duration of response (DOR)
Time Frame:24 months
Safety Issue:
Description:RECIST version 1.1
Measure:Toxicity (number of patients with treatment-related AE as assessed by CTCAE v4.03)
Time Frame:24 months
Safety Issue:
Description:number of patients with treatment-related AE as assessed by CTCAE v4.03
Measure:Health-Related Quality of Life (HRQOL)
Time Frame:24 months
Safety Issue:
Description:EORTC-LC13
Measure:To explore the mechanism of drug resistance in the treatment of specific gene mutation
Time Frame:24 months
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Guangdong Association of Clinical Trials

Trial Keywords

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

Last Updated

February 11, 2020