Efficacy and Safety of Durvalumab with Cisplatin/Carboplatin and Etoposide Plus Radiotherapy in Limited Disease Small Cell Lung Cancer
- Trial ID
- 2024-513433-20-00
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this Phase II randomized study is to evaluate the **superior efficacy** of the **Durvalumab** treatment group compared to the control group, as measured by **progression-free survival (PFS)** after 18 months in patients with limited disease small cell lung cancer. This objective is clinically relevant as it aims to determine the potential of Durvalumab to extend the period during which the disease does not worsen, which is a critical factor in the management and prognosis of small cell lung cancer.
Secondary objectives include assessing the superior efficacy of the Durvalumab treatment group versus the control group through various clinical endpoints: overall survival (OS), quality of life (QoL), overall response rate (ORR), disease control rate (DCR), and progression-free survival (PFS) at any other tumor assessments. Additionally, the study will evaluate the safety and tolerability of the treatment regimen. These secondary objectives are important for providing a comprehensive understanding of the treatment's impact on patient outcomes and its safety profile.
Participants
The clinical trial involves participants diagnosed with **Limited Disease Small Cell Lung Cancer**. The study population includes both male and female subjects aged 18 years and older. Participants are required to have a histologically confirmed diagnosis of limited disease small cell lung cancer, specifically at stages 2 and 3, according to UICC8 criteria. The trial includes individuals with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. Participants must have at least one measurable lesion as per RECIST 1.1 criteria and a body weight greater than 30 kg. Adequate normal organ function is a prerequisite, with specific laboratory values outlined for hemoglobin, absolute neutrophil count, platelet count, AST/ALT levels, serum bilirubin, and estimated glomerular filtration rate. The trial population was selected based on these criteria, ensuring the inclusion of individuals with a life expectancy of at least 12 weeks. The sponsor has not provided information regarding the total number of participants. The study does not specify any particular lifestyle considerations such as diet or physical activity. The trial includes a vulnerable population, indicating additional ethical considerations in the study design.
Plans and Procedures
The clinical trial is designed as a **randomized**, **double-blind**, controlled study to evaluate the efficacy and safety of combining **durvalumab** with standard chemotherapy and radiotherapy in patients with limited disease small cell lung cancer. The trial aims to assess the superior efficacy of the durvalumab treatment group compared to the control group, with the primary endpoint being progression-free survival (PFS) after 18 months. Secondary endpoints include overall survival, overall response rate, disease control rate, safety, tolerability, and symptom control assessed by patient-reported quality of life measures.
The trial will span approximately six years, with an estimated recruitment start date of September 30, 2020, and an estimated end date of September 30, 2026. Participants will be involved in the study for a maximum treatment period of 18 months. The study includes several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor treatment response and safety, and an end-of-study visit to assess final outcomes. Participants will be required to meet specific inclusion criteria, such as having histologically confirmed limited disease small cell lung cancer, adequate organ function, and a life expectancy of at least 12 weeks. Conditions that may lead to early termination from the study include significant adverse events or disease progression as determined by the investigator.
Participants will receive treatment via **intravenous use**, with the investigational product being a concentrate for solution for infusion. The trial involves the administration of durvalumab in combination with either cisplatin or carboplatin and etoposide, alongside concomitant radiotherapy. The study is not classified as a low-intervention trial and is categorized as a Phase II therapeutic exploratory trial. The trial's design ensures rigorous assessment of the investigational treatment's efficacy and safety, contributing valuable data to the understanding of treatment options for limited disease small cell lung cancer.
Treatment
The clinical trial involves the administration of **Durvalumab**, marketed as IMFINZI, which is a **concentrate for solution for infusion**. The pharmaceutical form is a solution for infusion, and it is administered via the **intravenous route**. The dosage is 50 mg/mL, with a maximum daily dose of 1500 mg and a total maximum dose of 33000 mg over a treatment period of 18 months. Durvalumab is a protein-based therapeutic agent, specifically classified under the ATC code L01XC28. The administration schedule and participant compliance are monitored to ensure adherence to the protocol.
**Etoposide** is another treatment used in the study, characterized as a chemical substance. It is administered in a pharmaceutical form denoted as PHF675, also via the intravenous route. The dosage is calculated based on body surface area, with a maximum daily dose of 100 mg/m² and a total maximum dose of 1800 mg/m² over a 15-week treatment period. Etoposide is classified under the ATC code L01CB01.
**Carboplatin** is included in the trial as a comparator treatment. It is a chemical substance administered intravenously, with a pharmaceutical form identified as PHF00230MIG. The dosing is based on a different unit, with a maximum daily dose of 5 units and a total maximum dose of 30 units over a 15-week period. Carboplatin is classified under the ATC code L01XA02.
**Cisplatin** is also utilized in the study, administered as a chemical substance in the form PHF00015MIG via the intravenous route. The dosage is determined by body surface area, with a maximum daily dose of 75 mg/m² and a total maximum dose of 450 mg/m² over a 15-week treatment period. Cisplatin is classified under the ATC code L01XA01. Compliance with the dosing schedule is monitored throughout the trial to ensure accurate data collection and participant safety.
Efficacy
The efficacy of the clinical trial will be assessed primarily through the measurement of **progression-free survival (PFS)** after 18 months, as per RECIST1.1 criteria, and iRECIST for the Durvalumab group. Secondary endpoints include additional assessments of PFS, overall survival (OS), overall response rate (ORR), disease control rate (DCR), and safety and tolerability. Symptom control will be evaluated using patient-reported quality of life (QoL) instruments, specifically the QLQ-C30, QLQ-LC13, and EQ-5D scales.
The trial is designed to compare the efficacy of Durvalumab in combination with Cisplatin or Carboplatin and Etoposide, alongside concomitant radiotherapy, against a control group receiving the same chemotherapy and radiotherapy regimen without Durvalumab. The primary endpoint, PFS, will be measured at the 18-month mark, while secondary endpoints will be assessed at various timepoints throughout the study. Data collection will involve validated scales and laboratory tests to ensure accuracy and reliability in the evaluation of these endpoints.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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; T2-4, 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: a. Hemoglobin ≥ 9.0 g/dL; b. Absolute neutrophil count (ANC) ≥ 1.5 x109/L; c. Platelet count ≥ 100 x109/L; d. AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal; e. Serum Bilirubin ≤ 1.5 x institutional upper limit of normal; f. 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
Exclusion Criteria
- 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: a. Patients with vitiligo or alopecia; b. Patients with hypothyroidism (e.g. following Hashimoto syndrome) stable on hormone replacement; c. Patients with any chronic skin condition that not required systemic therapy; d. Patients without active disease in the last 5 years may be included but only after consultation with the study physician; e. 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 non-melanoma 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: a. Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection); b. Systemic corticosteroids at physiologic doses not exceeding 10 mg/day of prednisone or its equivalent; c. 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: a. Women who are pregnant, nursing or who plan to become pregnant while in the trial; b. 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 and etoposide))
- Patients who are legally institutionalized
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Germany | Not Recruiting | 30 Sept 2020 | 105 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
IMFINZI 50 mg/mL concentrate for solution for infusion. | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS USE | 1500 | 18 | PRD6651398 |
CISPLATIN | Other | PHF00015MIG | INTRAVENOUS USE | 75 | 15 | SCP134220 |
ETOPOSIDE | Other | PHF675 | INTRAVENOUS USE | 100 | 15 | SCP100376572 |
CARBOPLATIN | Other | PHF00230MIG | INTRAVENOUS USE | 5 | 15 | SCP10337134 |