Phase II Umbrella Study Directed by Next Generation Sequencing

Carcinoma, Non-Small-Cell Lung Clinical Trial

— TRUMP  

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 Details — Status: Recruiting

Administrative data

• NCT number: NCT03574402
• Other study ID #: CTONG1702
• Status: Recruiting
• Phase: Phase 2
• Start date: July 9, 2018
• Est. completion date: December 30, 2024

Study information

• Verified date: December 2022
• Source: Guangdong Association of Clinical Trials
• Contact: Yi-Long Wu, Professor
• Phone: 862083827812
• Email: syylwu[@]live.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 400
• Est. completion date: December 30, 2024
• Est. primary completion date: December 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

Intervention

Drug:
• Avitinib Maleate
300mg orally (PO) twice daily (BID) on day 1-28.
• Afatinib
40mg orally once a day, 28 days as one cycle.
• Crizotinib
250mg PO QD on days 1-28. 28 days as one cycle.
• X-396
225mg PO QD on days 1-28. 28 days as one cycle.
• Chidamide
30mg orally twice weekly, 28 days as one cycle.
• Pyrotinib Maleate
400mg PO QD on days 1-28. 28 days as one cycle.
• AZD3759
200mg PO BID on days 1-28. 28 days as one cycle.
• Pirotinib
60mg PO QD/40mg PO BID on days 1-28. 28 days as one cycle.
• Nimotuzumab
400mg, iv gtt. on day 1,8,15. 21 days as one cycle.
• Pemetrexed
500mg/m^2, iv gtt. Q3W. 21 days as one cycle.
• Cisplatin
75mg/m^2, iv gtt. Q3W on day1. 21 days as one cycle.
• Sintilimab
200mg iv gtt. Q3W on day1. 21 days as one cycle.
• Gemcitabine
1g/m^2 iv gtt. on day1,8. 21 days as one cycle.
• Gemcitabine
1.25g/m^2 iv gtt. on day1,8. 21 days as one cycle.
• Carboplatin
AUC5 iv gtt. Q3W on day1. 21 days as one cycle.

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Guangdong Association of Clinical Trials	Chinese Thoracic Oncology Group

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rate (RR)	RECIST version 1.1	24 months
Secondary	Progression-free survival (PFS)	RECIST version 1.1	24 months
Secondary	Overall survival (OS)	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	48 months
Secondary	Disease control rate(DCR)	RECIST version 1.1	24 months
Secondary	Duration of response (DOR)	RECIST version 1.1	24 months
Secondary	Toxicity (number of patients with treatment-related AE as assessed by CTCAE v4.03)	number of patients with treatment-related AE as assessed by CTCAE v4.03	24 months
Secondary	Health-Related Quality of Life (HRQOL)	EORTC-LC13	24 months
Secondary	To explore the mechanism of drug resistance in the treatment of specific gene mutation		24 months