A Randomized Open-label Phase 2 Multicenter Study to Evaluate the Impact of Management Strategies on Gastrointestinal-Related Adverse Events in Patients With Non-Small Cell Lung Cancer Harboring EGFR Exon 20 Insertion Mutations Receiving TAK-788
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- 主要终点
- Number of Participants with Treatment Emergent Adverse Events (TEAEs) of ≥Grade 3 Diarrhea Occurring During the First 4 Cycles of TAK-788 Dosing
研究概览
简要总结
The purpose of the study is to characterize the incidence and severity of TAK-788-associated diarrhea in previously treated participants with locally advanced or metastatic non-small-cell lung cancer (NSCLC) whose tumors harbor EGFR exon 20 insertion mutations treated with TAK-788 when administered with or without intensive loperamide prophylaxis.
详细描述
The drug being tested in this study is called TAK-788. TAK-788 administered with or without antidiarrheal prophylaxis is being tested to evaluate the impact of management strategies on gastrointestinal-related adverse events in participants with non-small cell lung cancer harboring EGFR Exon 20 insertion mutations receiving TAK-788.
The study will enroll approximately 90 patients. Participants will be randomly assigned in 1:1 ratio (by chance, like flipping a coin) to one of the two treatment groups-
- Cohort 1
- Cohort 2
All participants will be asked to take TAK-788 capsules with or without a low-fat meal in Cohort 1 and TAK-788 capsule with antidiarrheal prophylaxis and with or without a low-fat meal in Cohort 2.
This is a multi-center trial and will be conducted worldwide. The overall time to participate in this study is approximately 2 years. Participants will make multiple visits to the clinic after receiving their last dose of drug for a follow-up assessment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 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
- •Diagnosed with histologically or cytologically confirmed nonsquamous cell locally advanced (not suitable for definitive therapy) or metastatic non-small-cell lung cancer (NSCLC) (Stage IIIB or IV) NSCLC; and, has received at least 1 prior line of therapy for this disease.
- •A documented epidermal growth factor receptor (EGFR) mutation with in-frame exon 20 insertion, confirmed as follows:
- •For sites located in the United States (US): assessment must be done by a certified laboratory functioning under the guidelines of the Clinical Laboratory Improvements Amendment (CLIA).
- •For site located outside of the US: assessment must be done by an accredited local laboratory.
- •Note: A documented EGFR in-frame exon 20 insertion or insertion-duplication includes but is not limited to one of the following:
- •A763_Y764insFQEA,
- •V769_D770insASV (also referred to as ASV duplication)
- •D770_N771insNPG
- •D770_N771insSVD (also referred to as SVD duplication)
- •H773_V774insNPH (also referred to as NPH duplication), or
- •Any other in-frame insertion mutation in the exon 20 [amino acids 739 -823].
- •The EGFR exon 20 insertion mutation can be either alone or in combination with other EGFR or HER2 mutations. The reported insertion-duplication can have been detected on either tissue or liquid biopsy using a well-validated test based on either polymerase chain reaction, sequencing or next-generation sequencing (NGS).
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •Minimum life expectancy of ≥3 months.
- •All toxicities from prior therapy have been resolved to ≤Grade 1, according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 or have resolved to baseline, at the time of first dose of TAK-788.
排除标准
- •Has been diagnosed with another primary malignancy other than NSCLC, except for the following:
- •Adequately treated non-melanoma skin cancer or cervical cancer in situ.
- •Definitively treated non-metastatic prostate cancer.
- •Non-NSCLC primary malignancies that are definitively relapse-free for ≥3 years.
- •Has unstable brain metastases to include previously untreated intracranial central nervous system (CNS) metastases or previously treated intracranial CNS metastases with radiologically documented new or progressing CNS lesions.
- •Brain metastases that are stable do not preclude eligibility if they have been treated with surgery and/or radiation, and have been stable without requiring corticosteroids to control symptoms within 7 days before randomization, and have no evidence of new or enlarging brain metastases.
- •Has a current spinal cord compression (symptomatic or asymptomatic that is detectable by radiographic imaging) or leptomeningeal disease (symptomatic or asymptomatic).
- •Currently has or has had a history of interstitial lung disease, to include radiation or drug related pneumonitis that requires/required steroid treatment.
- •Has an ongoing or active infection, to include but not limited to infections requiring intravenous antibiotics or has a known history of HIV. Testing for HIV is not required in the absence of history.
- •Note: Hepatitis B surface antigen-positive participants are allowed to enroll if hepatitis B virus (HBV) deoxyribonucleic acid (DNA) is below 1000 copies/mL in the plasma. Patients who are positive for anti-hepatitis C virus antibody can be enrolled but must not have detectable hepatitis C virus (HCV) RNA in the plasma.
- •Have uncontrolled hypertension. Participants with hypertension should be under treatment on study entry to control blood pressure.
- •A prolonged QTcF interval, or is being treated with medications known to be associated with the development of Torsades de Pointes.
- •Has a GI illness or disorder, including but not limited to a history of GI perforation, that could affect oral absorption of TAK-788.
研究组 & 干预措施
Cohort 1
TAK-788 160 mg, capsules, orally, once daily (QD) with or without a low-fat meal until disease progression or as assessed by the investigator during every 3-week cycle.
干预措施: TAK-788 (Drug)
Cohort 2
TAK-788 160 mg, capsules, orally, QD with or without a low-fat meal and antidiarrheal prophylaxis administered during the first 8 weeks of treatment until disease progression or as assessed by the investigator during every 3-week cycle.
干预措施: TAK-788 (Drug)
Cohort 2
TAK-788 160 mg, capsules, orally, QD with or without a low-fat meal and antidiarrheal prophylaxis administered during the first 8 weeks of treatment until disease progression or as assessed by the investigator during every 3-week cycle.
干预措施: Antidiarrheal prophylaxis (Drug)
结局指标
主要结局
Number of Participants with Treatment Emergent Adverse Events (TEAEs) of ≥Grade 3 Diarrhea Occurring During the First 4 Cycles of TAK-788 Dosing
时间窗: Approximately 15 Months
An Adverse Event (AE) is defined as any untoward medical occurrence in a participant who has enrolled in a study; it does not necessarily have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. Grading will be done using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) criteria. Per NCI CTCAE, Grade 1 scales as Mild; Grade 2 scales as Moderate; Grade 3 scales as severe or medically significant but not immediately life threatening; Grade 4 scales as life-threatening consequences; and Grade 5 scales as death related to AE.
次要结局
- Number of Participants With TEAEs of Diarrhea, Nausea, Vomiting and Other Adverse Event of Clinical Interest (AECIs) Occurring During the First 4 Cycles of TAK-788 Dosing(Approximately 15 Months)
- Progression Free Survival (PFS) as per RECIST Version 1.1(Approximately 15 Months)
- Health-Related Quality of Life (HRQoL) as Assessed by Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ) Score(Approximately 15 Months)
- Number of Participants with TEAEs of ≥Grade 3 Nausea and Vomiting Occurring During the First 4 Cycles of TAK-788 Dosing(Approximately 15 Months)
- Overall Response Rate (ORR) as per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1(Approximately 15 Months)
- Duration of Response as per RECIST Version 1.1(Approximately 15 Months)
- Health-Related Quality of Life (HRQoL) as Assessed European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 Score(Approximately 15 Months)
- Health-Related Quality of Life (HRQoL) as Assessed by EORTC Lung Cancer Module (QLQ-LC13) Score(Approximately 15 Months)