A Phase II Randomized Study to Evaluate the Efficacy and Safety of Cisplatin or Carboplatin / Etoposide and Concomitant Radiotherapy Combined With Durvalumab Followed by Maintenance Therapy With Durvalumab Versus Cisplatin or Carboplatin / Etoposide and Concomitant Radiotherapy in Patients With Limited Disease Small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- Michael Hopp
- 入组人数
- 105
- 试验地点
- 16
- 主要终点
- Progression-free survival (PFS)
研究概览
简要总结
Combination of concomitant Radio-Chemotherapy showed a significant improvement (Takada) of OS and PFS in limited disease SCLC patients. This clinical trial is a prospective, multicenter, randomized, open-label, parallel group phase II investigator initiated trial (ITT) to evaluate the efficacy and safety of Durvalumab in combination with Cisplatin/Etoposide/Radiotherapy in patients with limited disease small-cell lung cancer (SCLC).
详细描述
The trial is subdivided in a safety run-in phase and a randomized part with the induction phase (Radiochemotherapy ± Durvalumab and including prophylactic cranial irradiation (PCI; if clinically indicated and according to local standard)) followed by the maintenance phase. The trial starts with the safety run-in phase of 6 patients in Durvalumab group. After the completion of the first cycle of all 6 patients a safety interim analysis will be performed. Study should be discontinued if ≥ 2 out of 6 patients within safety run-in phase (first cycle):
- show more than 2 AEs CTCAE grade ≥3 related to study drug Durvalumab
- or develop pneumonitis (CTCAE grade ≥2)
- or drop out, Otherwise, the trial can continue with randomization. Eligible patients will be randomized to Durvalumab group or standard of care group 2:1.
The safety interim analysis was performed in Q4 2021. The independent DMC has recommended the continuation of the trial.
Induction phase:
Durvalumab group: Cisplatin (75 mg/m² (BSA) D1#) or alternatively Carboplatin (AUC 5 D1) and Etoposide (100 mg/m² (BSA) D1-3) once every 3 weeks for 4-6 cycles and concomitant Radiotherapy (60±6 Gy, 1.8-2 Gy/d or 45±1.5 Gy (1.5 Gy per fraction twice daily, with 4 hours or more between fractions) with start at latest at beginning of cycle 3, ideally during cycle 1) and additional Durvalumab (1500 mg once every 3 weeks) for 4-6 cycles according to randomization followed by prophylactic cranial irradiation (PCI, if clinically indicated and according to local standard at any time after completion of radio-chemotherapy))
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
- 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
- •Signed and dated informed consent of the subject must be available before start of any specific trial procedures
- •Male or female ≥ 18 years
- •Histological confirmed limited disease small cell lung cancer (stage 2 and 3; T1a-4, N1-3, M0 according UICC8 criteria; if primarius is not eligible as RECIST1.1 target lesion (in cases with T1a and T1b) at least one lymph node must meet RECIST1.1 criteria for target lesion (≥15 mm short axis))
- •Availability of tumor tissue or fresh tumor material for translational research by central lab testing
- •ECOG PS 0 - 1
- •At least one measurable lesion according RECIST 1.1
- •Body weight > 30 kg
- •Adequate normal organ function
- •Hemoglobin ≥ 9.0 g/dL
- •Absolute neutrophil count (ANC) ≥ 1.5 x109/L
- •Platelet count ≥ 100 x109/L
- •AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal
- •Serum Bilirubin ≤ 1.5 x institutional upper limit of normal
- •Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min for Carboplatin, ≥ 60 mL/min for Cisplatin, calculated by the Cockcroft-Gault formula
- •Life expectancy of at least 12 weeks in the discretion of the investigator
- •Ability of subject to understand nature, importance and individual consequences of clinical trial
排除标准
- •Extensive disease small cell lung cancer (Tx, Nx, M1; stage IV)
- •Major surgical process within 28 day prior first dose of IMP and/or Radiochemotherapy
- •History of allogenic organ transplantation
- •Active or prior documented autoimmune or inflammatory disorder (including inflammatory bowel disease [e.g. colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome or Wegener syndrome [granulomatosis with polyangiitis], Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.). The following are exceptions to this criterion:
- •Patients with vitiligo or alopecia
- •Patients with hypothyroidism (e.g. following Hashimoto syndrome) stable on hormone replacement
- •Patients with any chronic skin condition that not required systemic therapy
- •Patients without active disease in the last 5 years may be included but only after consultation with the study physician
- •Patients with celiac disease controlled by diet alone
- •Uncontrolled intercurrent illness (i.e. active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, interstitial lung disease, serious chronic gastrointestinal conditions (i.e. diarrhea), psychiatric illness)
- •History of another primary malignancy in the last 5 years, except adequately treated nonmelanoma skin cancer, adequately treated carcinoma in situ (without evidence of disease)
- •History of leptomeningeal carcinomatosis, or brain metastases
- •Known HIV positive and/or active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
- •Current or prior use of immunosuppressive medication within 14 days before the first dose.The following are exceptions to this criterion:
- •Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
- •Systemic corticosteroids at physiologic doses not exceeding 10 mg/day of prednisone or its equivalent
- •Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
- •Receipt of live attenuated vaccine within 30 days prior to the first dose of IMP
- •Participation in another clinical trial with an investigational product within the last 30 days (unless during follow-up period of an interventional study)
- •Known hypersensitivity to one of the ingredients
- •Medical or psychological conditions that would jeopardize an adequate and orderly completion of the trial
- •Pregnancy, lactation and contraception
- •Women who are pregnant, nursing or who plan to become pregnant while in the trial
- •Women of child-bearing potential (WOCBP) and men who are able to father a child, unwilling to be abstinent or use highly effective methods of birth control that result in a low failure rate of less than 1% per year when used consistently and correctly beginning at informed consent, for the duration of drug treatment and for the drug out washout period (90 days after last dose of Durvalumab and/or 6 months after last dose of cisplatin/carboplatin and etoposide).
- •Patients who are legally institutionalized
研究组 & 干预措施
Durvalumab
Induction phase: Durvalumab (1500 mg once every 3 weeks) for 4-6 cycles in combination with standard of care (Radiochemotherapy)
Maintenance phase: Durvalumab (1500 mg once every 4 weeks) until PD or unacceptable toxicities.
干预措施: Durvalumab (Drug)
standard of care
Induction phase: Radiochemotherapy according to guideline
Maintenance: Standard of care
干预措施: standard of care (Drug)
结局指标
主要结局
Progression-free survival (PFS)
时间窗: 18 months
Progression-free survival (PFS) after 18 months according to iRECIST
次要结局
- Progression-free survival (PSF) after other assessments(12 months)
- Overall survival (OS)(18 months)
- Quality of Life Questionnaire - Lung Cancer 13 (QLQ-LC13)(18 months)
- Adverse Events(18 months)
- Disease control rate (DCR)(18 months)
- Quality of Life Questionnaire - Cancer 30 (QLQ-C30)(18 months)
- Overall response rate (ORR)(18 months)
- EuroQol five dimension scale (EQ-5D)(18 months)
研究者
Michael Hopp
Head of Interdisciplinary Center for Clinical Studies (IZKS)
Johannes Gutenberg University Mainz