A Phase II Randomized, Double-Blind, Placebo-Controlled Study Evaluating Nintedanib Versus Placebo as Prophylaxis Against Radiation Pneumonitis in Patients With Unresectable NSCLC Undergoing Chemoradiation Therapy
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Portion of Common Terminology Criteria for Adverse Events Grade 2 or Higher Radiation Pneumonitis
研究概览
简要总结
This trial studies the side effects and how well nintedanib works compared to a placebo in treating against radiation-induced pneumonitis (inflammation of the lungs) in patients with non-small cell lung cancer that cannot be removed by surgery and are undergoing chemoradiation therapy. Nintedanib may help shrink or slow the growth of radiation-induced pneumonitis by blocking some of the enzymes needed for cells to grow and may prevent the growth of new blood vessels. It may also help reduce the recurrence of non-small cell lung cancer.
详细描述
PRIMARY OBJECTIVES:
I. To evaluate the safety of the combination of durvalumab with nintedanib in patients with unresectable Stage II/III/oligometastatic IV non-small cell lung carcinoma (NSCLC). (Phase I) II. To compare the rate of symptomatic radiation pneumonitis at 6 months after completion of chemoradiation in patients with unresectable stage II/III/ oligometastatic IV NSCLC who completed chemoradiation followed by nintedanib versus placebo. (Phase II)
SECONDARY OBJECTIVES:
I. To compare the quality of life (QOL) in patients who received nintedanib versus placebo during active treatment until 6 months after completion of treatment.
II. To compare the progression-free survival, overall survival and 1-year progression-free survival rate in patients who received nintedanib versus placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Double (Participant, Investigator)
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
- •Histologically or cytologically-proven non squamous cell NSCLC; mixed histology with small cell lung carcinoma (SCLC) component not allowed
- •Patients with stage II ? IV non squamous cell NSCLC who received at least 54 Gy of total planned thoracic radiation dose will be eligible; patients must have received at least one cycle of chemotherapy concurrently during the course of thoracic radiation; regimens allowed are platinum combinations with either etoposide or a taxane regardless of histology subtype; platinum with pemetrexed for patients with non-squamous NSCLC only; patients with oligometastatic stage IV cancer are eligible if they have received only one line of systemic therapy for their stage IV cancer prior to the concurrent chemoradiation phase
- •Patient must have had a complete response (CR)/partial response (PR)/stable disease (SD), 4-6 weeks after completing last fraction of radiation therapy
- •Eastern Cooperative Oncology Group (ECOG) performance score 0-2
- •Absolute neutrophil count (ANC) >= 1,500/uL
- •Platelet count >= 100,000/uL
- •Hemoglobin >= 9 g/dL
- •Total bilirubin =< normal or for those with Gilbert?s syndrome =< 1.5 times upper limit of normal (ULN) OR direct bilirubin normal (per institute standards)
- •Aspartate aminotransferase (AST) =< 1.5 x ULN; alanine aminotransferase (ALT) and AST =< 2.5 x ULN is acceptable if there is liver metastasis
- •Fertile patients must use adequate contraception
排除标准
- •Whole-brain radiotherapy (WBRT) < 14 days from the anticipated start of nintedanib/placebo administration
- •Squamous cell NSCLC
- •Unable to start nintedanib/placebo treatment between 4-8 weeks after completing the last dose of thoracic radiation
- •Active untreated brain or leptomeningeal metastases; in patients with treated central nervous system (CNS) metastases, eligible if symptoms controlled for at least 4 weeks; dexamethasone allowed if total daily dose does not exceed 2 mg
- •Major injuries or surgery (e.g., craniotomy) < 28 days from the start of nintedanib/placebo administration; wound should be healed prior to starting therapy
- •Second malignancies are allowed as long as the disease does not require active treatment with concomitant systemic cytotoxic chemotherapy, investigational or biologic therapy (e.g., anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA4] or human epidermal growth factor receptor 2 [HER2] monoclonal antibodies); hormone-related therapies (e.g., gonadotrophin releasing hormone (LHRH) agonists, tamoxifen, etc.) are allowed
- •Concurrent uncontrolled illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would increase the risk associated with study participation and/or limit compliance with study requirements
- •Inability to swallow study medication
- •Presence of active malabsorption disorder (e.g., flare episodes documented within the preceding 3 months, presence of symptoms requiring daily medications for control) or history of extensive small bowel resection
- •Known bleeding or thrombotic diathesis
- •History of arterial or venous thromboembolic event within 12 months prior to study participation
- •Active hemoptysis or history of clinically relevant hemoptysis as determined by the treating physician; patients who had history of transient minor hemoptysis after bronchoscopic biopsy are eligible unless deemed otherwise by the treating physician
- •Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or higher proteinuria
- •Investigational agent administered < 28 days prior to treatment with nintedanib. Last dose of systemic chemotherapy administered < 14 days prior to treatment with nintedanib
- •Known chronic active hepatitis B or hepatitis C; human immunodeficiency virus (HIV)-positive patients receiving or are candidates for antiretroviral therapy are also excluded
- •Pregnancy or breast feeding; female patients with child-bearing potential must have a negative pregnancy test (beta-human chorionic gonadotropin [B-HCG] test in urine or serum) prior to commencing study treatment
- •Creatinine > 1.5 x ULN or creatinine clearance levels (CrCL) < 45 mL/min
- •Centrally located tumors with radiographic evidence (computed tomography [CT] or magnetic resonance imaging [MRI]) of local invasion of major blood vessels
- •Therapeutic anticoagulation (except low-dose heparin and/or heparin flush as needed for maintenance of an in-dwelling intravenous devise) or anti-platelet therapy (except for low-dose therapy with acetylsalicylic acid < 325 mg per day)
- •Active or previous autoimmune disease requiring treatment within the past 2 years will exclude patients from receiving immune checkpoint inhibitor in this study. Exception allowed: endocrine conditions treated with necessary hormone replacement or other supportive medication; vitiligo, alopecia
研究组 & 干预措施
Arm I (nintedanib)
Beginning 4-8 weeks after completion of radiation therapy, patients receive nintedanib PO BID on days 1-28. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Nintedanib (Drug)
Arm I (nintedanib)
Beginning 4-8 weeks after completion of radiation therapy, patients receive nintedanib PO BID on days 1-28. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Quality-of-Life Assessment (Procedure)
Arm II (placebo)
Beginning 4-8 weeks after completion of radiation therapy, patients receive placebo capsules PO BID on days 1-28. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Placebo (Other)
Arm II (placebo)
Beginning 4-8 weeks after completion of radiation therapy, patients receive placebo capsules PO BID on days 1-28. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Quality-of-Life Assessment (Procedure)
Arm III (nintedanib, durvalumab)
Beginning 4-8 weeks after completion of radiation therapy, patients receive nintedanib PO BID on days 1-28 and standard of care durvalumab IV over 60 minutes on days 1 and 15. Treatment with nintedanib repeats every 28 days for up to 6 cycles and treatment with durvalumab repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Durvalumab (Biological)
Arm III (nintedanib, durvalumab)
Beginning 4-8 weeks after completion of radiation therapy, patients receive nintedanib PO BID on days 1-28 and standard of care durvalumab IV over 60 minutes on days 1 and 15. Treatment with nintedanib repeats every 28 days for up to 6 cycles and treatment with durvalumab repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Nintedanib (Drug)
Arm III (nintedanib, durvalumab)
Beginning 4-8 weeks after completion of radiation therapy, patients receive nintedanib PO BID on days 1-28 and standard of care durvalumab IV over 60 minutes on days 1 and 15. Treatment with nintedanib repeats every 28 days for up to 6 cycles and treatment with durvalumab repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Quality-of-Life Assessment (Procedure)
结局指标
主要结局
Portion of Common Terminology Criteria for Adverse Events Grade 2 or Higher Radiation Pneumonitis
时间窗: At 6 months after completion of chemoradiation
Will compare the rate of symptomatic radiation pneumonitis in patients who received nintedanib versus placebo. Assessed using the intent-to-treat principle and a one-sided exact test about the Cochran-Mantel-Haenszel correlation and regression test. The grade 2 or higher radiation penumonitis is identified by the Common Terminology Criteria for Adverse Events.
次要结局
- Number of Participants With Adverse Events, Graded According to Common Terminology Criteria for Adverse Events Version 4.0(Up to 2.5 years post-treatment)
- Progression-free Survival(1 year progression-free survival, with follow-up assessed up to 2.5 years post-treatment)
- Overall Survival(1 year survival, with follow-up assessed up to 2.5 years post-treatment)
- Percent Changes in Overall Quality of Life and Symptom Scores(Baseline up to 2.5 years post-treatment)
- Changes in Radiation Pneumonitis Scores(Baseline up to 2.5 years post-treatment)
- Responses Rates(Up to 2.5 years post-treatment)
- Percent Change in Pulmonary Function Tests(Baseline up to 2.5 years post-treatment)
- Biomarker Analysis(Up to 97 days post-treatment)