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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:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Not yet 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 MaleateAC0010Arm1: Avitinib Maleate
AfatinibGiotrifArm2: Chidamide plus Afatinib
CrizotinibXalkoriArm3: crizotinib
X-396ensartinibArm4: X396
ChidamideEpidazaArm2: Chidamide plus Afatinib

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

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.

        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.
      
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:Duration of response
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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Guangdong Association of Clinical Trials

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