Phase II Evaluation of Durvalumab Maintenance Therapy Post-Thoracic Chemoradiotherapy in Frail Patients with Limited Disease Small Cell Lung Cancer
- Trial ID
- 2024-512224-11-00
- Protocol
- UC-IMM-2106
- Sponsor
- Unicancer
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **progression-free survival (PFS)** in patients with frail limited disease small cell lung cancer (LD-SCLC) undergoing maintenance treatment with durvalumab following thoracic chemoradiotherapy (CRT). This is clinically relevant as PFS is a critical endpoint in assessing the efficacy of cancer therapies, providing insights into the duration patients remain free from disease progression.
Secondary objectives include:
- **Overall survival (OS)**, which measures the length of time from the start of treatment that patients are still alive, offering a comprehensive assessment of treatment impact on patient longevity.
- **Safety profile**, which evaluates the adverse effects associated with durvalumab, ensuring the treatment's risk-benefit ratio is acceptable.
- **Health-related quality of life (HRQoL)** using EORTC QLQ-C30 and LC13 questionnaires, which assesses the impact of the treatment on patients' overall well-being and daily functioning.
Participants
The clinical trial involves participants diagnosed with **Limited Disease Small Cell Lung Cancer** (LD-SCLC) who are considered frail, as defined by an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 2, or ECOG PS 0-1 and older than 70, or those who did not receive concomitant thoracic chemoradiotherapy (CRT) due to comorbidities. The study population includes both male and female subjects, with an age range that includes adults and older adults. Participants are required to have a histologically confirmed diagnosis of LD-SCLC and must not have received prior treatment for this condition. The trial population was selected based on specific health criteria, including adequate hematological, renal, and hepatic function, and a body weight greater than 30 kg. Lifestyle considerations such as diet and physical activity are not specified. The sponsor has not provided the total number of participants involved in the study. The trial includes a vulnerable population, indicating that special considerations are in place to ensure the safety and ethical treatment of all participants.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy of **durvalumab** as a maintenance treatment in patients with frail limited disease small cell lung cancer (LD-SCLC) following thoracic chemoradiotherapy (CRT). This is a Phase II, randomized, double-blind, controlled study. The trial aims to assess progression-free survival (PFS) as the primary endpoint, with overall survival (OS) and safety profile as secondary endpoints. The study is expected to run until February 2030, with recruitment having commenced in March 2023.
Participants will undergo a series of study visits, beginning with a screening visit to confirm eligibility based on specific inclusion criteria, such as age, performance status, and completion of thoracic CRT. The inclusion visit will follow, where participants will be randomized to receive either the investigational product or a control. Subsequent follow-up visits will be scheduled to monitor the participants' health status, treatment adherence, and any adverse events. The end-of-study visit will conclude the trial, assessing the final outcomes and collecting data for analysis.
The expected duration of participant involvement is up to 24 months, corresponding to the maximum treatment period with the investigational product. Conditions that may lead to early termination from the study include disease progression, unacceptable toxicity, withdrawal of consent, or any other reason deemed necessary by the investigator. Participants are required to comply with the protocol, including attending scheduled visits and undergoing necessary examinations throughout the trial duration.
Treatment
The clinical trial involves the administration of **durvalumab**, marketed under the name IMFINZI, which is a **concentrate for solution for infusion**. This experimental medication is provided in a concentration of 50 mg/mL and is intended for **intravenous infusion**. The maximum daily dose of durvalumab is 1500 mg, with a total maximum dose of 39000 mg over the course of the treatment. The treatment period is set for a maximum of 24 months. Durvalumab is a protein-based therapeutic agent, specifically classified under the ATC code L01XC28, and is produced by AstraZeneca AB. The administration of durvalumab is conducted following thoracic chemoradiotherapy in patients with limited disease small cell lung cancer (LD-SCLC) to evaluate its efficacy in terms of progression-free survival.
In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on the maintenance treatment with durvalumab. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen. The trial does not involve any pediatric formulations, and the product is not classified as an orphan drug. The administration of durvalumab is conducted under strict clinical conditions to ensure the safety and efficacy of the treatment in the study population.
Efficacy
The efficacy of the clinical trial will be assessed primarily through **Progression-Free Survival (PFS)**, which is defined as the time from inclusion until disease progression or death from any cause, as determined by the investigator using RECIST v1.1 criteria. Secondary endpoints include **Overall Survival (OS)**, defined as the time from inclusion to death due to any cause, with patients still alive at the time of analysis being censored at the last known alive date. Additionally, the safety profile will be evaluated by monitoring the occurrence of adverse events coded using NCI CTC-AE version 5.0. Quality of life will be assessed using the European Organization for Research and Treatment of Cancer (EORTC) core QL questionnaire, specifically the EORTC QLQ-C30 and LC13 questionnaires, which are designed for lung cancer patients.
Inclusion and Exclusion Criteria
Inclusion Criteria
- For Screening_Patient must have signed a first written informed consent form prior to screening visit and to any trial specific procedures
- For Screening_Patient must be willing and able to comply with the protocol for the duration of the trial including undergoing treatment and scheduled visits, and examinations including follow-up
- For Screening_Women of childbearing potential must have a negative serum beta-HCG test before the beginning of the trial, during the study treatment and for a period of at least 3 months after the last administration of the experimental drug
- For Screening_Limited disease (T0-T4, N0-N3 and M0) according to the TNM classification 8th edition or to the VALSG 2-stage classification. As per standard guidelines a complete radiological evaluation has to be performed within 28 days before the start of induction chemotherapy including all the radiological exams below: Total body PET- scan. Contrast enhanced CT-scan of thorax and upper abdomen. Contrast enhanced MRI or CT-scan of brain.
- For Screening_All sexually active men and women of childbearing potential must use an effective contraception method for the duration of study treatment and for 3 months after completing treatment
- For Screening_Patients affiliated to the social security system
- For Screening_Histological confirmation of SCLC
- For Screening_Measurable disease according to RECIST v1.1 criteria
- For Screening_Patients must not have been previously treated for the SCLC. Note: patients who have already begun the initial CRT are eligible
- For Screening_Patients ≥18 years old.
- For Inclusion_Patient must have signed a second written informed consent form prior to inclusion and to any specific trial procedure
- For Inclusion_Patients must belong to one of these groups at the screening visit after the thoracic CRT : ECOG PS 2. ECOG PS 0-1 and older than 70. ECOG PS 0-1 and who did not receive a concomitant thoracic CRT because of comorbidities (radiotherapy beginning before D1C3 of chemotherapy)._
- For Inclusion_Patients must have completed concomitant or sequential thoracic CRT by IMRT: Patients that received concomitant or sequential thoracic CRT must have received at least 60 Gy (one-daily fraction of 1.8-2 Gy) or 45 Gy twice daily (1.5 Gy per fraction) combined with cisplatin-etoposide regimen or with carboplatin AUC5 to AUC6. etoposide regimen. All other schedules/methods performed need to be centrally approved before the inclusion.
- For Inclusion_Confirmation of disease control (SD, CR or PR) at radiological assessment with contrast enhanced thorax and upper abdomen CT-scan or PET-CT and contrast enhanced brain CT-scan or MRI after the thoracic CRT according to RECIST v1.1
- For Inclusion_Use of brain MRI in case of PCI avoidance is mandatory. PCI has to be prescribed according to the investigator’s choice and the local recommendations_
- For Inclusion_HRQoL questionnaire performed
- For Inclusion_Adequate haematological function Haemoglobin >9 g/dL. Platelet count >100 x 109L. Neutrophil count >1.5 x 109L.
- For Screening_Body weight >30 kg.
- For inclusion_Adequate renal function with a creatinine clearance ≥40 ml/min calculated with the Cockcroft-Gault formula._
- For Inclusion_Adequate hepatic function: Total bilirubin <1.5 Upper limit of normal (ULN). AST and ALT <2.5 ULN. Alkaline phosphatase <2.5 ULN.
- For Inclusion_Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
- For Screening_Patients can be candidate to concomitant or sequential thoracic CRT by IMRT: Patients have to receive at least 60 Gy (one daily fraction of 1.8-2 Gy) or 45 Gy twice daily (1.5 Gy per fraction) combined with cisplatin-etoposide regimen orwith carboplatin AUC5 to AUC6 etoposide regimen
- For Screening_Patients that received previous thorax radiotherapy may be eligible if they can receive the CRT schedule planned in the clinical study according to previous irradiation fields and, in any case, after the medical monitor agreement
- For Inclusion_Body weight >30 kg
Exclusion Criteria
- History of another primary malignancy except for a. Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of durvalumab and of low potential risk for recurrence. b. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. c. Adequately treated carcinoma in situ without evidence of disease.
- Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
- Active or prior documented autoimmune or inflammatory disorders (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. Any chronic skin condition that does not require 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.
- Any concurrent chemotherapy, immune checkpoint inhibitors, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
- History of leptomeningeal carcinomatosis
- Major surgical procedure (as defined by the Investigator) including surgical resection of the primary disease, within 28 days prior to the first dose of IMP.
- History of allogenic organ transplantation
- History of active primary immunodeficiency
- Known active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, or TB testing in line with local practice) and hepatitis B and hepatitis C (positive hepatitis C virus [HCV] antibody, hepatitis B virus [HBV] surface antigen [HBsAg] or HBV core antibody [anti-HBc]).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 HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA. Patients known to have been tested positive for human immunodeficiency virus (HIV) (positive HIV 1/2 antibodies) are not eligible.
- Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. 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 to exceed 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 durvalumab. Note: Included patients should not receive live vaccine whilst receiving durvalumab and up to 30 days after the last dose of durvalumab.
- Patients with known or suspected hypersensitivity to durvalumab or any of its excipients
- Patients who participated in another therapeutic trial within the 30 days prior to the start of the trial (screening phase included).
- Prior randomisation or treatment in a previous durvalumab clinical study regardless of treatment arm assignment.
- Female patients who are pregnant or breast feeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy
- Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
- Persons deprived of their liberty or under protective custody or guardianship
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Not Recruiting | 24 Mar 2023 | 29 |
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 INFUSION | 1500 | 24 | PRD6651398 |