Optimization of Treatment With Brigatinib in Patients With Advanced NSCLC Harboring an ALK Rearrangement by LAT at the Time of Best Response: A Multicenter Open Phase Two Trial (OPTALK)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 45
- 试验地点
- 27
- 主要终点
- Progression free survival (PFS) centrally assessed
研究概览
简要总结
The goal of this clinical trial is to learn if the treatment by systemic Brigatinib (ALUNBRIG®) associated to local ablative therapy (LAT) treatment is improved if administered when the brigatinib works best in participants presenting an advanced non-small cells lung cancer with an ALK gene anomaly (this anomaly produces a defective protein that is responsible for the multiplication of cancer cells).
This clinical trial is expected to involve 45 participants in several sites in France.
Advanced non-small cell lung cancer (NSCLC) participants with ALK rearrangements treated with brigatinib in first line of non-curable setting will be screened.
If the disease assessment done between 3 to 9 months after initiation of brigatinib shows:
- a tumor response or stabilization (according to RECIST 1.1)
- a disease which meets the definition of an oligometastatic disease (five metastatic lesions or less and a maximum of two lesions per organ)
- all tumor targets are accessible to a local ablative therapy (confirmed by an expert panel of clinicians before inclusion): surgery, stereotactic radiosurgery (SRS). For liver, adrenal, or other metastases, percutaneous thermal ablation will be accepted.
Participants will be asked to visit the clinic:
- for eligibility criteria assessment prior to LAT
- for LAT
- every 8 weeks for checkups and tests the first year after LAT
- and then every 12 weeks, for a maximum period of 3 years.
Eligible patients will benefit from local ablative therapy with continuation of brigatinib.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 years or older at diagnosis.
- •Stage 3 non eligible for chemoradiotherapy or stage 4 NSCLC, histologically or cytologically confirmed NSCLC.
- •Tyrosine Kinase Inhibitor (TKI) treatment naïve.
- •ALK rearrangements identified by a validated technique (either Immunohistochimy (IHC), fluorescence in situ hybridization (FISH) or Ribonucleic Acid (RNA)seq, in tissue or liquid biopsy)
- •Stable disease or response after initiation brigatinib treatment (at least 3 to 9 months) according to RECIST 1.1
- •At least one site of residual site for LAT (ie. participant should not have a complete response)
- •Oligometastatic disease (five metastatic lesions or less and a maximum of two lesions per organ) de novo or induced
- •Eligible for local ablative treatment possible (either alone or combined): surgery, minimally invasive form of surgical radiosurgery (Stereotactic Radio Surgery (SRS)) (18 to 20 Gy in single fraction) or radiotherapy (SBRT) (27 to 54 Gy in 3 fractions or 45 to 50 Gy in 5 fractions), radiofrequency or cryotherapy (=thermoablation)
- •An Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤
- •Life expectancy above 12 weeks as assessed by treating investigator.
- •Brain metastases at inclusion are allowed if asymptomatic
- •No history of other malignant tumor during the previous 5 years, except for adequately treated carcinomas (in situ cervical carcinoma, basal cell carcinoma, squamous cell skin carcinoma) and low-grade localized prostate cancer (Gleason <6).
- •Adequate organ function, as demonstrated by laboratory results prior to the first administration of study treatment: normal hepatic function (bilirubin ≤1.5 x upper limit of normal (ULN), alanine aminotransferase (ALA T) and aspartate aminotransferase (ASAT) ≤2.5 x ULN or ≤5 x ULN in case of liver metastases), renal function (calculated creatinine clearance (CrCl, using local formula) above 45 ml/mn), normal hematological function (absolute neutrophil count
- •≥1.5 x 109/L and/or platelets ≥100 x 109/L, hemoglobin ≥8 g/dL), normal coagulation function (International Normalized Ratio (INR) or prothrombin time ≤1.5 x ULN and activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) ≤1.5 x ULN unless the patient is receiving anticoagulant therapy)
- •For patients of childbearing potential: Women of childbearing potential should use effective non-hormonal contraception during treatment with brigatinib and for at least 4 months following the final dose. Men with female partners of childbearing potential should use effective contraception during treatment and for at least 3 months after the last dose of brigatinib.
- •Signed informed consent to participate in the study
- •Affiliation with or benefit from French social security
排除标准
- •NSCLC without known ALK rearrangements
- •Neuroendocrine tumor (even in case of mixed tumors).
- •Uncontrolled and untreated superior cava syndrome.
- •Unstable symptomatic brain metastases despite corticosteroid
- •Leptomeningeal, pericardial, pleural and mesenteric lesions, lymphangitic spread (any tumoral lesions not amenable to definitive local therapy). Peri tumoral lymphangitic spread around a tumor, but limited to a lobe, may be treated by surgery).
- •Serious concurrent conditions during the previous 6 months (severe or unstable angina pectoris, coronary or peripheral artery bypass graft of <6 months, class 3 or 4 congestive heart failure, ischemic stroke, grade ≥2 peripheral neuropathy, psychiatric or neurological disorders that may interfere with the patient's understanding of the study or with his/her informed consent.
- •Severe or non-controlled systemic diseases deemed incompatible with the protocol.
- •Severe infections within 4 weeks prior to inclusion, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia.
- •Psychological, family, social, or geographical factors that may interfere with the monitoring of the patient as defined by the protocol.
- •Any protected person (legal person protected by legal protection [guardianship, tutorship], person deprived of liberty, pregnant woman, breastfeeding woman, and minor).
- •Patients who participated in other concomitant studies unless observational and received study therapy or used an investigational device within 4 weeks prior to start of study treatment
- •Known allergies or adverse reactions to the study drugs
- •Lung function not compatible with surgery or radiation
研究组 & 干预措施
Clinical Trial population
All advanced non-small cell lung cancer (NSCLC) patients with ALK rearrangements treated with brigatinib in first line of non-curable setting will be screened.
If the disease assessment done between 3 to 9 months after initiation of brigatinib shows:
- a tumor response or stabilization (according to RECIST 1.1)
- a disease which meets the definition of an oligometastatic disease (five metastatic lesions or less and a maximum of two lesions per organ)
- all tumor targets are accessible to a local ablative therapy (confirmed by an expert panel of clinicians before inclusion): surgery, stereotactic radiosurgery (SRS), For liver, adrenal, or other metastases, percutaneous thermal ablation will be accepted.
Eligible patients will benefit from local ablative therapy with continuation of brigatinib.
干预措施: Blood samples for Hematology (Biological)
Clinical Trial population
All advanced non-small cell lung cancer (NSCLC) patients with ALK rearrangements treated with brigatinib in first line of non-curable setting will be screened.
If the disease assessment done between 3 to 9 months after initiation of brigatinib shows:
- a tumor response or stabilization (according to RECIST 1.1)
- a disease which meets the definition of an oligometastatic disease (five metastatic lesions or less and a maximum of two lesions per organ)
- all tumor targets are accessible to a local ablative therapy (confirmed by an expert panel of clinicians before inclusion): surgery, stereotactic radiosurgery (SRS), For liver, adrenal, or other metastases, percutaneous thermal ablation will be accepted.
Eligible patients will benefit from local ablative therapy with continuation of brigatinib.
干预措施: Blood samples for Chemistry (Biological)
Clinical Trial population
All advanced non-small cell lung cancer (NSCLC) patients with ALK rearrangements treated with brigatinib in first line of non-curable setting will be screened.
If the disease assessment done between 3 to 9 months after initiation of brigatinib shows:
- a tumor response or stabilization (according to RECIST 1.1)
- a disease which meets the definition of an oligometastatic disease (five metastatic lesions or less and a maximum of two lesions per organ)
- all tumor targets are accessible to a local ablative therapy (confirmed by an expert panel of clinicians before inclusion): surgery, stereotactic radiosurgery (SRS), For liver, adrenal, or other metastases, percutaneous thermal ablation will be accepted.
Eligible patients will benefit from local ablative therapy with continuation of brigatinib.
干预措施: Blood sample for liver function tests (Biological)
Clinical Trial population
All advanced non-small cell lung cancer (NSCLC) patients with ALK rearrangements treated with brigatinib in first line of non-curable setting will be screened.
If the disease assessment done between 3 to 9 months after initiation of brigatinib shows:
- a tumor response or stabilization (according to RECIST 1.1)
- a disease which meets the definition of an oligometastatic disease (five metastatic lesions or less and a maximum of two lesions per organ)
- all tumor targets are accessible to a local ablative therapy (confirmed by an expert panel of clinicians before inclusion): surgery, stereotactic radiosurgery (SRS), For liver, adrenal, or other metastases, percutaneous thermal ablation will be accepted.
Eligible patients will benefit from local ablative therapy with continuation of brigatinib.
干预措施: Pregnancy test (Biological)
Clinical Trial population
All advanced non-small cell lung cancer (NSCLC) patients with ALK rearrangements treated with brigatinib in first line of non-curable setting will be screened.
If the disease assessment done between 3 to 9 months after initiation of brigatinib shows:
- a tumor response or stabilization (according to RECIST 1.1)
- a disease which meets the definition of an oligometastatic disease (five metastatic lesions or less and a maximum of two lesions per organ)
- all tumor targets are accessible to a local ablative therapy (confirmed by an expert panel of clinicians before inclusion): surgery, stereotactic radiosurgery (SRS), For liver, adrenal, or other metastases, percutaneous thermal ablation will be accepted.
Eligible patients will benefit from local ablative therapy with continuation of brigatinib.
干预措施: Tumour assessment (Procedure)
Clinical Trial population
All advanced non-small cell lung cancer (NSCLC) patients with ALK rearrangements treated with brigatinib in first line of non-curable setting will be screened.
If the disease assessment done between 3 to 9 months after initiation of brigatinib shows:
- a tumor response or stabilization (according to RECIST 1.1)
- a disease which meets the definition of an oligometastatic disease (five metastatic lesions or less and a maximum of two lesions per organ)
- all tumor targets are accessible to a local ablative therapy (confirmed by an expert panel of clinicians before inclusion): surgery, stereotactic radiosurgery (SRS), For liver, adrenal, or other metastases, percutaneous thermal ablation will be accepted.
Eligible patients will benefit from local ablative therapy with continuation of brigatinib.
干预措施: Local Ablative Therapy (LAT) (Procedure)
结局指标
主要结局
Progression free survival (PFS) centrally assessed
时间窗: From the start date of treatment up to the disease progression as per central reading or for a maximum of 3 years.
PFS is defined as the time from Brigatinib initiation until tumor progression or death from any cause according to RECIST v1.1, evaluated by the expert panel. Radiological evaluation of the target lesions(s) will be performed at the following time points: Screening, then every 8 weeks during the first year then every 12 weeks thereafter. An expert panel of blinded clinicians will anonymously review the radiological evaluations and confirm/infirm the Investigator's assessment. Each Investigator must provide all the documents necessary to assess the various endpoints. Progression occurring before 2 years will be considered for the endpoint. Patients alive without progression will be censored at the last radiological assessment.
次要结局
- Progression free survival (PFS) locally assessed(From the start date of treatment up to the disease progression as per local reading or for a maximum of 3 years.)
- Overall survival (OS)(From the start of treatment until death or lost of follow-up or for a maximum of 3 years)
- Median PFS(From the start of treatment until death or lost of follow-up or for a maximum of 3 years)
- Safety and tolerability(From the enrolment of the participant up to until 90 days after the last administration of radiotherapy or until 60 days after the last surgery / thermal ablation)
- Duration of Treatment (DOR)(From the start date of treatment up to stop date of treatment or for a maximum of 3 years)