Magnesium Supplementation in Addition to Standard Chemo-immunotherapy in Patients With Locally Advanced Unresectable Stage III or Metastatic Stage IV Non-small Cell Lung Cancer (NSCLC). A Double-blind Randomized Multicenter Phase II/III Study.
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 230
- 试验地点
- 18
- 主要终点
- Primary endpoint of Phase II part: Progression-free survival (PFS)
研究概览
简要总结
This study investigates whether adding magnesium to the standard chemo-immunotherapy for advanced non-small cell lung cancer (NSCLC) can improve treatment outcomes. Magnesium is important for immune function, and low levels during chemotherapy are common. Participants are randomly assigned to receive either magnesium or a placebo, both as infusions and tablets. Neither the participants nor the doctors know who receives which treatment. The study compares the two groups to see if magnesium helps and how well it is tolerated.
详细描述
This randomized, double-blind, placebo-controlled, multicenter phase II/III trial evaluates the efficacy and safety of intravenous and oral magnesium supplementation in addition to standard first-line chemo-immunotherapy in patients with unresectable stage III or metastatic stage IV non-small cell lung cancer (NSCLC).
Platinum-based chemotherapy frequently induces hypomagnesemia, which may impair T-cell mediated anti-tumor immunity and reduce the effectiveness of immune checkpoint inhibitors. This trial investigates whether correcting magnesium deficiency can enhance immune response and improve clinical outcomes.
The primary objective of the phase II portion is to assess the safety and feasibility of magnesium supplementation and its impact on PFS. If interim analysis confirms tolerability without significant additional toxicity, the trial will seamlessly expand into a phase III component with overall survival (OS) as the primary endpoint.
Secondary objectives include objective response rate (ORR), duration of response (DoR), adverse events (AEs) and serious adverse events (SAEs), health-related quality of life (HRQoL), immune-related biomarkers and magnesium levels.
Patients are randomized to receive either:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Blinding procedures Patient randomization into the two treatment arms is double-blind. Neither the patient nor any of the investigators who are involved in the conduct of the trial, or the analysis of the trial data have knowledge of the assigned treatment arm.
This level of blinding is maintained throughout the conduct of the trial unless there are compelling medical or safety reasons to alleviate the unblinding.
On the sponsor's side, the Clinical Research Associates (CRA) performing source data verification, and the CDM-DM performing data management remain blinded for the entire duration of the trial.
Blinding is performed by the authorized pre-wholesaler upon randomization of the patient.
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
- •Written informed consent according to Swiss law and ICH GCP E6 regulations before registration and prior to any trial specific procedures;
- •Histologically or cytologically confirmed diagnosis of NSCLC (adeno-, squamous-, large cell carcinoma or NSCLC not otherwise specified);
- •Patients planned for systemic first-line therapy with a combination of a carboplatin-based doublet chemotherapy and a PD-1 / PD-L1 targeting immune checkpoint inhibitor;
- •Patients not eligible for immune checkpoint inhibitor monotherapy irrespective of PD-L1 expression;
- •Locally advanced unresectable stage III or metastatic stage IV disease (defined as TNM, according to 8th edition) not eligible for curative surgery and/or definitive (curative intended) chemoradiotherapy;
- •No sensitizing EGFR mutation, METex14 skipping mutation, BRAF V600E mutation, ALK/ROS1/RET, NTRK1/2 gene rearrangements, HER2 mutations, amplifications detected in primary tumor or metastases;
- •Have not received prior systemic treatment for their metastatic NSCLC. Patients who received adjuvant, neoadjuvant chemotherapy or chemoradiotherapy with curative intent for nonmetastatic disease are eligible if the therapy was completed at least 12 months prior to the diagnosis of metastatic disease;
- •Patients with treated and stable CNS metastases are eligible, provided they meet the following criteria:
- •No ongoing requirement for corticosteroids as therapy for CNS disease; anticonvulsants at a stable dose allowed
- •No stereotactic radiation or whole-brain radiation within 14 days prior to registration.
- •Patients with known HIV-infection, who are at low risk of AIDS-related outcomes, are eligible, provided they meet the following criteria:
- •CD4+ T-cell counts are ≥ 350 cells/ųL
- •No history of AIDS-defining opportunistic infection within past 12 months
- •Patients have been on antiretroviral therapy (ART) for > 4 weeks before registration and have a HIV viral load < 400 copies/mL;
- •Patients with a prior malignancy and treated with curative intention are eligible if the treatment of that malignancy was completed at least 2 years before registration and the patient has no evidence of disease at registration. Less than 2 years is acceptable for malignancies with low risk of recurrence and/or no late recurrence;
- •Measurable disease per RECIST v1.134);
- •Age ≥ 18 years;
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1;
- •Adequate bone marrow function as per local guidelines;
- •Adequate hepatic function: total bilirubin ≤ 1.5 x ULN (except for patients with Gilbert's disease ≤ 3.0 x ULN), AST and ALT ≤ 2.5 x ULN, or ≤ 5 x ULN under the assumption that abnormal values are a result of NSCLC;
- •Adequate renal function defined by stable estimated glomerular filtration rate (eGFR) ≥ 45 mL/min/1.73 m2 (according to CKD-EPI formula);
- •Women of childbearing potential must use highly effective contraception (see chapter 9.4), are not pregnant or lactating and agree not to become pregnant during trial treatment and until 6 months after the last dose of investigational drug. A negative pregnancy test before inclusion into the trial is required for all women of childbearing potential.
- •Men agree not to donate sperm or to father a child during trial treatment and until 6 months after the last dose of investigational drug.
排除标准
- •Plasma magnesium concentration < 0.4 mmol/l or > 1.2 mmol/L
- •Treatment with any anti-cancer therapy within 21 days prior to registration (excluding hormonal therapy or anti-cancer surgery). Any previous anti-cancer therapy must have been administered with curative intent;
- •Treatment with radiotherapy within 14 days prior to registration (except for local pain control);
- •Patients planned for cisplatin-based chemo-immunotherapy;
- •Treatment with any other experimental drug within 28 days of registration;
- •Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV), unstable angina pectoris, history of myocardial infarction within the last six months, serious arrhythmias requiring medication (with exception of atrial fibrillation or paroxysmal supraventricular tachycardia);
- •Atrioventricular (AV) block of any degree unless being treated with cardiac pacemakers;
- •Bradycardia <40/min at steady state;
- •Active chronic Hepatitis C or Hepatitis B infection or any uncontrolled active systemic infection, needing antibiotic treatment within 14 days before registration;
- •Known history of tuberculosis, known history of relevant primary immunodeficiency, known history of allogeneic organ transplant, receipt of live attenuated vaccine within 28 days prior to registration;
- •Diagnosis of myasthenia gravis;
- •Concomitant or prior use of immunosuppressive medication within 28 days before registration, with the exceptions of:
- •intranasal and inhaled corticosteroids
- •systemic corticosteroids ≤ 10 mg/day of prednisone, or a dose equivalent corticosteroid,
- •premedication for chemotherapy;
- •Prior treatment with peroral or intravenous magnesium 14 days prior to registration;
- •Patient not willing to stop the use of peroral magnesium treatment including over the counter or lifestyle products;
- •Any concomitant drugs contraindicated for use with the trial drug according to the approved product information;
- •Known hypersensitivity to any of the trial drugs;
- •Any other serious underlying medical, psychiatric, psychological, familial or geographical condition, which in the judgment of the investigator may interfere with the planned staging, treatment and follow-up, affect patient compliance or place the patient at high risk from treatment-related complications.
研究组 & 干预措施
Placebo
Platinum-based chemo-immunotherapy every 3 weeks
+ Placebo
- intravenous at day 1 of each therapy cycle
- peroral thrice daily (day 1-21)
干预措施: Microcrystalline cellulose (Other)
Magnesium
Platinum-based chemo-immunotherapy every 3 weeks
+ Magnesium
- intravenous at day 1 of each therapy cycle
- peroral thrice daily (day 1-21)
干预措施: Magnesium Diasporal (Drug)
Magnesium
Platinum-based chemo-immunotherapy every 3 weeks
+ Magnesium
- intravenous at day 1 of each therapy cycle
- peroral thrice daily (day 1-21)
干预措施: Magnesiocard (Drug)
Placebo
Platinum-based chemo-immunotherapy every 3 weeks
+ Placebo
- intravenous at day 1 of each therapy cycle
- peroral thrice daily (day 1-21)
干预措施: Isotonic saline solution 0.9% (Other)
结局指标
主要结局
Primary endpoint of Phase II part: Progression-free survival (PFS)
时间窗: From randomization to PD or death, up to 10 years
PFS defined as time from randomization to progression according to RECIST 1.1 criteria or death. Patients not experiencing an event will be censored at the date of the last available assessment before initiation of a new anti-cancer treatment, if any.
Primary endpoint of Phase III part: Overall survival (OS)
时间窗: From randomization to PD or death, up to 10 years
OS defined as the time from randomization until death due to any cause. Patients not experiencing an event will be censored at the last date they were known to be alive.
次要结局
- Toxicity - Intermediate endpoint for the adaptive decision to expand, or not, into a Phase III(All adverse events: from baseline until end of treatment, deaths: until end of follow-up, up to 10 years)
- Number of participants discontinued any treatment component.(from baseline until end of treatment, deaths: until end of follow-up, up to 10 years)
- Event-free survival (EFS)(From randomization to PD, 2nd tumor or death, up to 10 years)