Durvalumab in frail and elder patients with metastatic non-small-cell lung carcinoma
- Conditions
- metastatic non-small cell lung cancer (NSCLC)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-003963-20-DE
- Lead Sponsor
- AIO-Studien-gGmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 200
1.Written informed consent and any locally-required authorization (EU Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
2.Age = 70 years at time of study entry and/or Charlson-Comorbidity-Index (CCI) >1 and/or Performance status ECOG >1
3.Histologically confirmed diagnosis of metastatic NSCLC and no targetable molecular alterations (EGFRwt; ALKtransl-) and not amenable to cisplatinum-based standard-combination chemotherapy.
4.Patients with measurable disease (at least one uni-dimensionally measurable target lesion not previously irradiated, by CT-scan or MRI) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) are eligible.
5.A formalin fixed, paraffin-embedded (FFPE) tumor tissue block (archival less than 3 years old or recent) or a minimum of 10 unstained slides of tumor sample (slices must be 2-3 µm in thickness and less than 90 days and collected on Superfrost slides provided by the sponsor) must be available for biomarker (PD-L1) evaluation. Biopsy should be excisional, incisional or core needle 18 gauge or larger. Fine needle aspiration is inappropriate.
6.No prior chemotherapy or any other systemic therapy for metastatic NSCLC. Patients who have received prior platinum-containing adjuvant, neoadjuvant, or definitive chemoradiation for locally advanced disease are eligible, provided that progression has occurred >6 months from last therapy.
7.Prior radiotherapy and surgery are allowed if completed 4 weeks (for minor surgery and palliative radiotherapy for bone pain: 2 weeks) prior to start of treatment and patient recovered from toxic effects or associated adverse events.
8.Adequate blood count, liver-enzymes, and renal function:
•Haemoglobin = 9.0 g/dL
•Absolute neutrophil count (ANC) = 1.5 x 109/L (> 1500 per mm3)
•Platelet count = 100 x 109/L (>100,000 per mm3)
•Serum bilirubin = 1.5 x ULN. This will not apply to subjects with confirmed Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.
•AST (SGOT)/ALT (SGPT) = 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be = 5x ULN
•Serum creatinine CL>30 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance
9.Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits, examinations including follow up and appropriate contraception.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 200
1.Mixed small-cell lung cancer and NSCLC histology
2.Mean QT interval corrected for heart rate (QTc) =470 ms calculated from 3 electrocardiograms (ECGs) using Fredericia’s correction, except for asymptomatic prolongations
3.History of another primary malignancy except
- local prostate cancer without need for systemic treatment (e.g. active surveillance, operation without need for adjuvant treatment) and malignancies treated with curative intent and with no known active disease >2 years before the first dose of study drug and of low potential risk for recurrence
- adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
- adequately treated carcinoma in situ without evidence of disease (e.g. cervical cancer in situ)
4.Pre-existing peripheral neuropathy of Grade = 2
5.Brain metastasis or spinal cord compression unless asymptomatic or treated and stable off steroids and anti-convulsants for at least 1 month prior to study treatement.
6.Active or prior documented autoimmune disease within the past 2 years. NOTE: Subjects with vitiligo, Grave’s disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
7.Active or prior documented inflammatory bowel disease (e.g., Crohn’s disease, ulcerative colitis)
8.History of primary immunodeficiency
9.History of allogeneic organ transplant
10.History of hypersensitivity to durvalumab or any excipient
11.History of hypersensitivity to any of the comparator agents
12.Medication that is known to interfere with any of the agents applied in the trial.
13.Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent
14.Clinical diagnosis of active tuberculosis
15.Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab
16.Male patients of reproductive potential who are not employing an effective method of birth control (failure rate of less than 1% per year)
17.Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
18.Participation in another clinical study with an investigational product during the last 30 days before inclusion
19.Any previous treatment with a PD-1 or PD-L1 inhibitor, including durvalumab
20.Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid
21.Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) = 21 days prior to the first dose of study drug or =4 half-lifes of the agent administered, which ever comes first.
22.Previous enrollment or ra
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