A Phase IIIB Study in Untreated Patients with Extensive-Stage Small Cell Lung Cancer
- Conditions
- Extensive-Stage Small Cell Lung CancerMedDRA 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
- EUCTR2020-002328-35-ES
- Lead Sponsor
- AstraZeneca Farmacéutica Spain, S.A
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 101
1. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and this protocol.
2. Provision of signed and dated, written informed consent obtained from the patient/legal representative prior to performing any protocol-related procedures. The ICF process is described in Appendix A 3.
3. Male or female =18 years at the time of screening.
4. Patients must have histologically- or cytologically-documented extensive-stage SCLC (stage IV [T any, N any, M1a/b/c] or with T3-4 due to multiple lung nodules that are too extensive or have tumor/nodal volume that is too large to be encompassed in a tolerable radiation plan, according to American Joint Committee on Cancer Stage, 8th edition).
a. Patients who had received chemoradiotherapy for LS-SCLC and have experienced a treatment-free interval of at least 6 months since last chemotherapy, radiotherapy, or chemoradiotherapy cycle, can be included under investigator criteria.
b. Patients may be included if they either do not have brain metastases, or have brain metastases that are asymptomatic, or have brain metastases that have been treated at least 2 weeks prior to study treatment and are currently receiving 10 mg/day or less of prednisone or equivalent. Patients with suspected brain metastases at screening should have a CT/MRI of the brain prior to enrollment.
5. Patients must be considered suitable to receive a platinum-based chemotherapy regimen as 1st line treatment for ES-SCLC. Chemotherapy must contain either cisplatin or carboplatin in combination with etoposide.
6. World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 at enrolment/
a. Note: a maximun of 30% of total patients with PS2 will be allowed; once this limit is met, additional enrolled patients must have PS 0-1.
7. At least 1 lesion, not previously irradiated, that can be accurately measured at baseline as =10 mm in the longest diameter (except lymph nodes which must have a short axis =15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and that is suitable for accurate repeated measurements as per RECIST 1.1 guidelines.
8. No prior exposure to immune-mediated therapy for cancer including, but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD-L1, and anti-programmed cell death ligand 2 (anti-PD-L2) antibodies.
9. Adequate hematologic and organ function, defined by the following laboratory results obtained within 14 days prior to first Durvalumab dose:
a. ANC = 1500 cells/µL without granulocyte colony-stimulating factor support
b. Platelet count = 100,000/µL without transfusion
c. Hemoglobin = 9.0 g/dL
d. INR or aPTT = 1.5 × upper limit of normal (ULN); This applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose.
e. AST and ALT = 2.5 × ULN, with the following exceptions: Patients with documented liver metastases: AST and/or ALT = 5 × ULN; Patients with documented liver or bone metastases: alkaline phosphatase = 5 × ULN.
f. Serum bilirubin = 1.5 × ULN; Patients with known Gilbert disease who have serum bilirubin level = 3 × ULN may be enrolled.
g. Measured or calculated creatinine clearance: >60mL/min for patients on cisplatin and >45mL/min for patients on carboplatin, as determined by Cockcroft-Gault (using actual body weight)
10. Evidence of post-menopausal status or negat
1. History of allogeneic organ transplantation.
2. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease). 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 with celiac disease controlled by diet alone
Note: Patients without active disease in the last 5 years may be included but only after consultation with AstraZeneca.
3. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
4. 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/social situations that would limit compliance with treatment requirements or compromise the ability of the patient to give written informed consent.
5. Malignancies other than SCLC within 3 years prior to screening if the patient has no evidence of disease, with the exception of those with a negligible risk of metastasis or death (e.g., expected 5-year OS > 90%) treated with expected curative outcome.
6. History of leptomeningeal carcinomatosis.
7. History of active primary immunodeficiency.
8. Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1 / 2 antibodies).
a. NOTE: 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.
9. Has a paraneoplastic syndrome (PNS) of autoimmune nature, requiring systemic treatment (systemic steroids or immunosuppressive agents) or has a clinical symptomatology suggesting worsening of PNS.
10. Known allergy or hypersensitivity to Durvalumab (IMFINZI), etoposide, carboplatin, cisplatin, or any of their excipients.
11. Medical contraindication to etoposide-platinum (carboplatin or cisplatin)-based chemotherapy
12. Has received prior systemic treatment for ES-SCLC.
13. Planned consolidation chest radiation therapy.
14. Receipt of live attenuated vaccination within 30 days prior to the first dose of Durvalumab (IMFINZI). Note: Patients, if enrolled, should not receive live vaccine whilst receiving Durvalumab (IMFINZI) and up to 30 days after the last dose of Durvalumab (IMFINZI).
15. Major surgical procedure (as defined by the treating physician) within 28 days prior to the first dose of Durvalumab (IMFINZI). Note: Local surgery of isolated lesions for palliative intent is acceptable.
16. Prior exposure to any immune-mediated therapy, including, but not limited to, anti-CTLA-4, anti-PD-1, anti-PD-L1, or anti-PD-L2 antibodies, including Durvalumab/(IMFINZI).
17. Current or prior use of immunosuppressive medication within 14 da
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method