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

NCT03058094 | Withdrawn Phase 3

• 1 other identifier: AEGIS2:AC201602AVTN04
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 21

Brief Summary

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.

Conditions

NSCLC

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  To assess the Progression-Free Survival (PFS) of AC0010 in EGFR T790M mutation-positive patients with advanced non-small cell lung cancer (NSCLC).

  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.

Secondary Outcomes (5)

• Objective Response Rate (ORR)

  Baseline up to 28 days after completion of study drug, assessed up to 24 months.

• Duration of Response (DoR)

  From occurring of CR or PR until progression or the date of death from any cause, whichever came first, assessed up to 24 months.

• Disease Control Rate (DCR)

  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.

• Overall Survival (OS)

  From the date of randomization to death or end of study, which is assessed up to 36 months.

• Patient Reported Outcomes by EORTC QLQ-C30 Questionnaire

  Baseline up to 28 days after completion of study drug, assessed up to 24 months.

Other Outcomes (1)

• Incidence of toxicity, grading with CTCAE 4.03

  From the date of randomization until end of treatment,which is assessed up to 24 months

Study Arms (2)

AC0010

EXPERIMENTAL

AC0010, 300mg, orally, BID with a 21-day cycle

Drug: AC0010

Chemotherapy

ACTIVE COMPARATOR

pemetrexed 500 mg/m2 + cisplatin 75 mg/m2 on day one of 21-day cycle, with total of 4-6 cycles.

Drug: Pemetrexed; Drug: Cisplatin 75mg/m2

Interventions

Pemetrexed DRUG

Pemetrexed will be administered as an intravenous infusion over 10 minutes on Day 1 of each 21-day cycle. Folic acid will be administered 1-2 weeks prior to the 1st dose, then daily during the treatment period until 21days post the last dose. Vitamin B12 will be administered on the same day of pemetrexed infusion during the treatment period. Corticosteroid will be adminstered on the day prior to, on the day, and on the day after infusion.

Also known as: Alimta

Chemotherapy

Cisplatin 75mg/m2 DRUG

Cisplatin will be administered as an intravenous infusion.

Also known as: cis-platinum

Chemotherapy

AC0010 DRUG

300mg, orally, BID

Also known as: AC0010MA

AC0010

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, aged between 18-75 years old.
• Histological or cytological confirmed diagnosis of locally or metastatic NSCLC (stage IIIB/IV).
• Locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy.
• Radiological proven disease progression while on first generation EGFR TKIs.
• At least one measurable disease according to RECIST 1.1.
• Confirmation of tumor EGFR sensitive mutation positive in previous tumor samples, including G719X, exon 19 deletion, L858R, L861Q.
• Confirmation of tumor harboring of T790M mutation by central lab with a biopsy sample taken after failure of first generation EGFR TKIs.
• 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
• Anti-cancer treatment prior to EGFR TKIs including chemotherapy, radiotherapy and other anti-cancer drugs for advanced stage is not allowed.
• 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.
• ECOG performance status 0 to1.
• Life expectancy more than 3 months.

You may not qualify if:

• Undiagnosed by pathology.
• HCV antibody positive, active hepatitis B (hepatitis B virus carrier can be recruited)
• HIV antibody positive, other acquired immunodeficiency disease and congenital immunodeficiency disease. Patients with organ transplantation.
• 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.
• 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.
• Uncontrolled pleural and pericardial effusion.
• Patients who have used high-dose glucocorticoids or other immunosuppressive agents within 1 month prior to screening.

Sponsors & Collaborators

• Hangzhou ACEA Pharmaceutical Research Co., Ltd.: lead
• Cancer Institute and Hospital, Chinese Academy of Medical Sciences: collaborator

Study Sites (21)

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100000, China

Location

Chinese General PLA Hospital

Beijing, Beijing Municipality, 100000, China

Location

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100000, China

Location

Xinqiao Hospital Army Medical University

Chongqing, Chongqing Municipality, 400000, China

Location

Fujian Cancer Hospital

Fuzhou, Fujian, 350000, China

Location

Fuzhou General Hospital of Nanjing Military Command

Fuzhou, Fujian, 350000, China

Location

Tumor Hospital of Hebei Province

Shijiazhuang, Hebei, 050000, China

Location

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, 150000, China

Location

Henan Cancer Hospital

Zhengzhou, Henan, 450000, China

Location

Jiangsu Province Hospital

Nanjing, Jiangsu, 210000, China

Location

Nanjing General Hospital

Nanjing, Jiangsu, 210000, China

Location

The First Affiliated Hospital of Dalian Medical University

Dalian, Liaoning, 116000, China

Location

The second Hospital of Dalian Medical University

Dalian, Liaoning, 116000, China

Location

The First Affiliated Hospital of China Medical University

Shenyang, Liaoning, 110000, China

Location

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200000, China

Location

Sichuan Cancer Hospital & Institute

Chengdu, Sichuan, 610000, China

Location

West China Hospital,Sichuan University

Chengdu, Sichuan, 610000, China

Location

Tianjin Medical University Cancer Institute & Hospital

Tianjin, Tianjin Municipality, 300000, China

Location

The First Affiliated Hospital,Zhejiang University

Hangzhou, Zhejiang, 310000, China

Location

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310000, China

Location

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Beijing, 100021, China

Location

MeSH Terms

Interventions

Pemetrexed; Cisplatin; abivertinib

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Yuankai Shi, MD.

  Cancer Institute and Hospital, Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2016
• First Posted: February 20, 2017
• Study Start: December 1, 2018
• Primary Completion: December 1, 2019
• Study Completion: January 1, 2020
• Last Updated: February 4, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (21)