TREASURE- Thoracic RadiothErapy with Atezolizumab in Small cell lUng canceR Extensive disease

Phase 1

• Conditions: Small cell lung cancer extensive disease; MedDRA version: 21.1Level: PTClassification code 10041068Term: Small cell lung cancer extensive stageSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-003916-29-AT
• Lead Sponsor: Frankfurter Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-03-24
• Last Update Posted: 8 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 104

Inclusion Criteria

1. Fully-informed written consent and locally required authorization (European Union [EU] Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
2. Age = 18 years.
3. Histologically or cytologically confirmed ED SCLC as defined according to the Veterans Administration Lung Study Group staging system.
4. Measurable ED SCLC according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. In cases of CR or PR without residual measurable disease after 4 cycles of induction therapy, patients may still be included. In such cases No Evidence of Disease (NED)” should be reported in eCRF.
5. ECOG performance-status score of 0 or 1 at screening
6. Any response after four cycles of standard chemo-immunotherapy (carboplatin, etoposide, atezolizumab) defined as CR/PR or thoracic SD with CR/PR of extrathoracic lesions a per RECIST 1.1
7. Thoracic treatment volume considered treatable using acceptable radiation fields as judged by a radiation oncologist
8. 28 ± 7 days between last administration of chemo-immunotherapy (carboplatin, etoposide, atezolizumab) and randomization.
9. Patients with a history of treated CNS metastases are eligible, if there is no ongoing requirement for corticosteroids as therapy for CNS disease. Before randomization, MRI of brain (with contrast, unless contraindicated) is recommended in subjects with suspected or known brain metastases, as per local standard. Patients with asymptomatic brain metastases that do not require local therapy with irradiation (whole brain irradiation) can be included. In ambiguous cases, consultation with the LKP or his/her delegate is advised.
10. No previous radiotherapy to lung and mediastinal lymph nodes within the past 5 years before the first dose of study drug.
11. Availability of pre-treatment tumor tissue specimen
12. The patient is willing and able to comply with the protocol for the duration of the study, including hospital visits for treatment and scheduled follow-up visits and examinations.
13. FEV1 = 40% (%Soll)
14. Adequate bone marrow and renal function including the following:
• Hemoglobin = 9.0 g/dL;
• Absolute neutrophil count = 1.0 x 10^9/L;
• Platelets =75x 10^9/L;
• Calculated creatinine clearance =30 mL/min as determined by the Cockcroft-Gault equation
15. Adequate hepatic function (with stenting for any obstruction, if required) including the following:
• Serum bilirubin = 3 x institutional upper limit of normal (ULN);
• AST (SGOT) / ALT (SGPT) and alkaline phosphatase = 2.5x ULN
Following exceptions apply:
• Patients with documented liver metastases: AST and/or ALT = 5x ULN
• Patients with documented liver or bone metastases: alkaline phosphatase = 5x ULN.
16. Female patients with reproductive potential must have a negative urine or serum pregnancy test within 7 days prior to start of trial.
17. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
• Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for

Exclusion Criteria

1.Previous treatment with CD137 agonists, immune-checkpoint blockade therapies, anti-PD-1, or anti-PD-L1 therapeutic antibodies (with the exclusion of prior immunotherapy as defined in inclusion criterion 6).
2.Prior therapy for limited-stage SCLC with curative intent.
3.Prior radiotherapy of lung and mediastinal lymph nodes within the past 5 years before the first dose of study drug.
4.Oxygen-dependent medical condition.
5.History or current radiology suggestive of interstitial lung disease (ILD) (including but not limited to idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP)/cryptogenic fibrosing alveolitis (CFA)), non-infectious pneumonitis, drug-induced pneumonitis, idiopathic pneumonitis.
6.Criterion removed.
7.Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study, or during the follow-up period of an interventional study.
8.Participation in another clinical study with an investigational product within 21 days prior to the first dose of the study treatment.
9.Any concurrent chemotherapy, investigational product (IMP), biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer related conditions (eg, hormone replacement therapy) is acceptable.
10.Major surgery (as defined by the Investigator) within 4 weeks prior to enrollment into the study; patients must have recovered from effects of any major surgery. Note: Local non-major surgery for palliative intent is acceptable.
11.Active or prior documented autoimmune or inflammatory disorders (including but not limited to diverticulitis [with the exception of diverticulosis], celiac disease, systemic lupus erythematosus, Sarcoidosis, or Wegener’s syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis). The following are exceptions to this criterion:
oPatients with vitiligo or alopecia
oPatients with hypothyroidism (e.g., following Hashimoto’s disease) stable on hormone replacement
oPatients with controlled Type I diabetes mellitus on an insulin regimen
oAny chronic skin condition that does not require systemic therapy
oPatients without active disease in the last 5 years may be included but only after consultation with the study physician.
12.Active, uncontrolled inflammatory bowel disease [e.g. ulcerative colitis or Crohn's disease]. Patients in stable remission for more than 1 year may be included.
13.Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, interstitial lung disease, gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations 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.
14.History of another primary malignancy except for:
oMalignancy treated with curative intent and with no known active disease = 3 years before the first dose of IMP and of low potential risk for recurrence
oAdequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
oAdequately treated carcinoma in situ without evidence of disease
15.History of active primary immunodeficiency
16.History of allogenic organ or tissue transplantation.
17.Clinical diagnosis of

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The objective of this study is to investigate the treatment efficacy of combining thoracic radiotherapy (TRT) with the IMpower133 regimen in the upfront treatment of ED SCLC patients.<br>The study is designed in an attempt to increase the efficacy of atezolizumab maintenance after induction with chemo/atezolizumab by adding radiotherapy.;Secondary Objective: Additionally, with this study, we aim to determine the safety and tolerability of the combination of immunological and radiological treatment in the first-line setting of advanced SCLC.<br>Furthermore, we aim to collect blood, stool and tissue samples prospectively for the separate translational program.;Primary end point(s): The primary endpoint is overall survival (OS), defined as time from randomization to death due to any cause. The primary endpoint will be evaluated as a time-to-event variable using a Cox proportional hazards model.;Timepoint(s) of evaluation of this end point: at study end / after LVLS