Study of Durvalumab or Placebo Given along with Platinum-based Chemo-radiation Therapy in Patients with Locally Advanced where cancer cannot be removed completely through surgery for Non-small Cell Lung Cancer (Stage III)
- Conditions
- Health Condition 1: null- Unresectable Non-small Cell Lung Cancer (Stage III)
- Registration Number
- CTRI/2018/07/014783
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Closed to Recruitment of Participants
- Sex
- Not specified
- Target Recruitment
- 0
Informed consent
1.Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
2.Provision of signed and dated, written ICF prior to any mandatory study-specific procedures, sampling, and analyses.
3.18 years or older at the time of signing the ICF. In Japan, patients must be 20 years or older at the time of signing the ICF.
4.Histologically or cytologically documented NSCLC who present with locally advanced, unresectable (Stage III) disease (according to Version 8 of the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology [IASLC Staging Manual in Thoracic Oncology 2016]).
?Except for overt cT4 disease, nodal status N2 or N3 should be proven by biopsy, via endobronchial ultrasound, mediastinoscopy, or thoracoscopy. Absent biopsy, nodal status should be confirmed with whole body F-fluoro-deoxyglucose positron emission tomography, plus contrast-enhanced computed tomography (CT) in addition to or in combination with PET.
?Mandatory brain magnetic resonance imaging (MRI preferred) or high-quality brain CT with IV contrast at the time of staging.
5.World Health Organization (WHO)/ Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 at enrollment and randomization.
6.Patients with at least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 Target Lesion (TL) at baseline. Tumor assessment by CT or MRI must be performed within 28 days prior to randomization.
7.Tumor sample requirements:
i.Mandatory provision of an archived tumor tissue block (or at least 15 newly cut unstained slides) less than or equal to 3 years old. If an archival sample is not available, provision of a recent (less than or equal to 3 months) tumor biopsy is mandated.
ii.The provision of an additional recent (less than or equal to 3 months) tumor biopsy is optional, provided that a biopsy procedure is technically feasible and the procedure is not associated with unacceptable clinical risk.
8.Must have a life expectancy of at least 12 weeks at randomization
9.Pre- or post-bronchodilator forced expiratory volume 1 of 1.0 L or greater than 40 percentage predicted value and diffusing capacity of the lung for carbon monoxide greater than 30 percentage predicted value. Pulmonary function testing results for up to 8 weeks prior to registration are permitted.
10.Adequate organ and marrow function at enrollment and randomization as defined below:
iii.Hemoglobin greater than or equal to 9.0 g/dL
iv.Absolute neutrophil count greater than 1.5 × 109/L
v.Platelet count greater than 100 × 109/L
vi.Serum bilirubin less than or equal to 1.5 × upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert’s syndrome, who will be allowed in consultation with their physician.
vii.Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 2.5 × ULN; for patients with hepatic metastases, ALT and AST less than or equal to 5 × ULN.
viii.Measured creatinine clearance (CL) greater than 40 mL/min or calculated CL greater than 40 mL/min as determined by Cockcroft-Gault (using actual body weight)
11.Genetics research study (optional)
For inclusion in the optional (DNA) genetics research
Patients should not enter the study if any of the following exclusion criteria are fulfilled:
Medical conditions
1.History of allogeneic organ transplantation
2.Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [example colitis or Crohns 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:
i.Patients with vitiligo or alopecia
ii.Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement
iii.Any chronic skin condition that does not require systemic therapy
iv.Patients without active disease in the last 5 years at randomization may be included but only after consultation with the study physician
v.Patients with celiac disease controlled by diet alone
3.Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, ILD, serious chronic 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
4.History of another primary malignancy except for
vi.Malignancy treated with curative intent and with no known active disease greater than or equal to 5 years before the first dose of IP and of low potential risk for recurrence
vii.Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
viii.Adequately treated carcinoma in situ without evidence of disease
5.History of leptomeningeal carcinomatosis
6.History of active primary immunodeficiency
7.Active infection including tuberculosis (TB) (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 (HCV), or human immunodeficiency virus (positive HIV 1/2 antibodies). 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 antibody are eligible only if polymerase chain reaction is negative for HCV RNA
8.Mixed small cell and NSCLC histology.
9.Known allergy or hypersensitivity to any of the IPs or any of the IP excipients.
10.Any medical contraindication to treatment with platinum-based doublet chemotherapy as listed in the local labelling.
11.Patients whose radiation treatment plans are likely to encompass a volume of whole lung receiving greater than or equal to 20 Gy in total (V20) of more than 35 percentage of lung volume. V20s up to 37% will be permitted and viewed as a minor deviation, provided that the treating radiation oncologist believes this level of exposure is within patient tolerance.
12.Planned radiation cardiac dose V50 greater than 25 percentage.
13.Patients who have disease considered for surgical treatment as part of their care plan, s
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To assess the efficacy of durvalumab + Standard of Care Chemo Radiation Therapy compared with placebo + Standard of Care Chemo Radiation in terms of Progression Free Survival and Objective Response RateTimepoint: Approximately 4 years
- Secondary Outcome Measures
Name Time Method