Clinical Trials /

A Study Comparing AC0010 and Chemotherapy in Patients With Advanced NSCLC Who Have Progressed Following Prior EGFR TKI

NCT03058094

Description:

A Phase III, Open-Label, Randomized Multicenter Study to Compare AC0010 and Pemetrexed/Cisplatin in Patients With Advanced NSCLC Who Have Progressed Following Prior EGFR TKI.

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

Withdrawn

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study Comparing AC0010 and Chemotherapy in Patients With Advanced NSCLC Who Have Progressed Following Prior EGFR TKI
  • Official Title: A Phase III, Open-Label, Randomized Multicenter Study to Compare AC0010 and Pemetrexed/Cisplatin in Patients With Advanced NSCLC Who Have Progressed Following Prior EGFR TKI

Clinical Trial IDs

  • ORG STUDY ID: AEGIS2:AC201602AVTN04
  • NCT ID: NCT03058094

Conditions

  • NSCLC

Interventions

DrugSynonymsArms
PemetrexedAlimtaChemotherapy
Cisplatin 75mg/m2cis-platinumChemotherapy
AC0010AC0010MAAC0010

Purpose

A Phase III, Open-Label, Randomized Multicenter Study to Compare AC0010 and Pemetrexed/Cisplatin in Patients With Advanced NSCLC Who Have Progressed Following Prior EGFR TKI.

Detailed Description

      This is a phase III, open label, randomized study assessing AC0010 (300 mg, BID) versus
      pemetrexed/cisplatin (4-6 cycles) in patients with advanced NSCLC, who have progressed
      following prior therapy with EGFR-TKI.

      Patients must provide a biopsy for central confirmation of T790M mutation positive. Eligible
      patients will be randomized (2:1) into AC0010 group or pemetrexed/cisplatin group. Patients
      in chemotherapy group can cross-over to AC0010 treatment when patients experience disease
      progression or intolerability of chemotherapy. The primary objective of the study is to
      compare the PFS of AC0010 and pemetrexed/cisplatin.
    

Trial Arms

NameTypeDescriptionInterventions
AC0010ExperimentalAC0010, 300mg, orally, BID with a 21-day cycle
  • AC0010
ChemotherapyActive Comparatorpemetrexed 500 mg/m2 + cisplatin 75 mg/m2 on day one of 21-day cycle, with total of 4-6 cycles.
  • Pemetrexed
  • Cisplatin 75mg/m2

Eligibility Criteria

        Inclusion Criteria:

          1. Male or female, aged between 18-75 years old.

          2. Histological or cytological confirmed diagnosis of locally or metastatic NSCLC (stage
             IIIB/IV).

          3. Locally advanced or metastatic NSCLC, not amenable to curative surgery or
             radiotherapy.

          4. Radiological proven disease progression while on first generation EGFR TKIs.

          5. At least one measurable disease according to RECIST 1.1.

          6. Confirmation of tumor EGFR sensitive mutation positive in previous tumor samples,
             including G719X, exon 19 deletion, L858R, L861Q.

          7. Confirmation of tumor harboring of T790M mutation by central lab with a biopsy sample
             taken after failure of first generation EGFR TKIs.

          8. Adequate organ function:

               -  Bone marrow reserve: Absolute neutrophil count ≥1.5 ´ 109/L,. Platelet count
                  ≥100´ 109/L , Hemoglobin≥9 g/dL

               -  Liver function: Alanine aminotransferase (ALT) and Aspartate aminotransferase
                  (AST) ≤2.5 × the upper limit of normal (ULN) or <5 times ULN in the presence of
                  liver metastases; Total bilirubin ≤1.5 × ULN

               -  Kidney function: Creatinine ≤1.5 × ULN

          9. Anti-cancer treatment prior to EGFR TKIs including chemotherapy, radiotherapy and
             other anti-cancer drugs for advanced stage is not allowed.

         10. Resolved toxicities from prior therapy less than CTCAE grade 1 (except alopecia) and
             minimum 7 days of washout period from previous erlotinib, gefitinib or icotinib.

         11. ECOG performance status 0 to1.

         12. Life expectancy more than 3 months.

         13. Patients without CNS metastases or asymptomatic patients with brain metastases. End of
             local therapy for brain metastases, including radiotherapy and surgery is required ≥28
             days prior to beginning of screening.

         14. Provision of signed informed consent.

        Exclusion Criteria:

          1. Undiagnosed by pathology.

          2. HCV antibody positive, active hepatitis B (hepatitis B virus carrier can be recruited)

          3. HIV antibody positive, other acquired immunodeficiency disease and congenital
             immunodeficiency disease. Patients with organ transplantation.

          4. Patients received new aided/aided system therapy with palindromia in 12 months, the
             new aided/aieded system therapy is considered to be previous first-line treatment.

          5. Condition of organ system:

               -  Large field radiation or radiation field covered more than 30% bone marrow within
                  4 weeks of enrollment.

               -  A past history of interstitial lung disease, drug-induced interstitial lung
                  disease or other active interstitial lung disease with clinical proof

               -  Idiopathic pulmonary fibrosis (IPF).

               -  In the investigator opinion, any severe or uncontrolled disease, such as unstable
                  or uncontrolled respiratory, cardiovascular, liver or kidney diseases.

               -  Any unstable system disease including refractory hypertension, unstable angina
                  pectoris, congestive heart-failure, liver and renal disease, metabolic disease.

               -  Patients with other malignant tumor in 5 years (except cured cervical carcinoma
                  in situ, Basal cell carcinomas, squamous cell carcinoma)

               -  A past history of neurological disorder or mental disorder including epilepsy and
                  dementia.

               -  Patients with chronic gastrointestinal diseases, inability to swallow medication,
                  malabsorption syndrome or previous significant bowel resection that would
                  preclude adequate absorption of AC0010.

          6. Uncontrolled pleural and pericardial effusion.

          7. Patients who have used high-dose glucocorticoids or other immunosuppressive agents
             within 1 month prior to screening.

          8. Patient with symptomatic CNS metastases.

          9. Significant cardiovascular disease, such as New York Heart Association cardiac disease
             (Class II or greater), myocardial infarction within 6 months, heart block with second
             degree or greater, QTcB > 430ms(male)or > 450ms(female).

         10. Patients receiving medication known to prolong QT interval and potent inducers and
             inhibitors of CYP3A4 within 4 weeks of fist dose of AC0010.

         11. Patients prove 1ml plasma to site's central lab after signing informed consent and the
             test results show the medication of AZD9291.

         12. Patients who have been registered and received the study treatment or withdrawn from
             the study cannot be enrolled.

         13. Patients receive unrelated surgery more than 14 days prior to the screening.

         14. Pregnant and lactating women.

         15. Women with childbearing potential are defined as all women who are physiologically
             able to have a pregnancy, unless they are using an efficient contraceptive method
             during treatment and within 7 days after discontinuation of treatment.

         16. Men who have sexual intercourse unless they use a condom during sexual intercourse
             during treatment and 7 days after discontinuation of treatment and do not impregnate
             their sexual partners during the period. Vasectomized males are also required to use
             condoms to prevent the transmission of drugs through semen.

         17. Patients who are considered by the investigator as inappropriate to participate in the
             study.
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-Free Survival (PFS)
Time Frame:From the date of randomization until the date of first documented progression or the date of death from any cause, whichever came first, assessed up to 24 months.
Safety Issue:
Description:To assess the Progression-Free Survival (PFS) of AC0010 in EGFR T790M mutation-positive patients with advanced non-small cell lung cancer (NSCLC).

Secondary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:Baseline up to 28 days after completion of study drug, assessed up to 24 months.
Safety Issue:
Description:To assess the overall objective response rate (ORR) of AC0010 in EGFR T790M mutation-positive patients with advanced non-small cell lung cancer (NSCLC).
Measure:Duration of Response (DoR)
Time Frame:From occurring of CR or PR until progression or the date of death from any cause, whichever came first, assessed up to 24 months.
Safety Issue:
Description:To assess the overall objective response rate (ORR) of AC0010 in EGFR T790M mutation-positive patients with advanced non-small cell lung cancer (NSCLC).
Measure:Disease Control Rate (DCR)
Time Frame:From the date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months.
Safety Issue:
Description:To assess the Disease Control Rate (DCR) of AC0010 in EGFR T790M mutation-positive patients with advanced non-small cell lung cancer (NSCLC).
Measure:Overall Survival (OS)
Time Frame:From the date of randomization to death or end of study, which is assessed up to 36 months.
Safety Issue:
Description:To assess the Overall Survival (OS) of AC0010 in EGFR T790M mutation-positive patients with advanced non-small cell lung cancer (NSCLC).
Measure:Patient Reported Outcomes by EORTC QLQ-C30 Questionnaire
Time Frame:Baseline up to 28 days after completion of study drug, assessed up to 24 months.
Safety Issue:
Description:To assess the safety of AC0010 in EGFR T790M mutation-positive patients with advanced non-small cell lung cancer (NSCLC).

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Hangzhou ACEA Pharmaceutical Research Co.,Ltd.

Last Updated