Health Condition 1: C349- Malignant neoplasm of unspecifiedpart of bronchus or lung
Conditions
Interventions
Intervention1: Durvalumab monotherapy: Durvalumab in combination with placebo saline solution IV q4w for up to 4 doses/cycles each, followed by durvalumab q4w. A total of 26 cycles. Durvalumab in comb
Sponsors
AstraZeneca AB
AstraZeneca Pharma India Ltd
Eligibility
Inclusion criteria
Inclusion criteria: 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.Provision of signed and dated written genetic informed consent prior to collection of sample for genetic analysis. 4.Age 18 to 75 years at the time of screening. For patients aged Type of patient and disease characteristics 5. Histologically or cytologically documented limited-stage SCLC (Stage I-III SCLC [T any, N any, M0] according to the American Joint Committee on Cancer Staging Manual [AJCC Cancer Staging Manual, 8th Edition] or the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology [IASLC Staging Manual in Thoracic Oncology 2016]), ie, patients whose disease can be encompassed within a radical radiation portal. Patients who are Stage I or II must be medically inoperable. 6.World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 at enrollment and randomization. 7.Received 4 cycles of platinum-based chemotherapy concurrent with RT, which must be completed within 1 to 42 days prior to randomization and the first dose of IP. i.The chemotherapy regimen must contain platinum and etoposide, as per local standard-of-care regimens. ii.For patients who are recovering from toxicities associated with initial treatment or for whom PCI is indicated by local standard of care, the first dose of IP may be delayed by up to 42 days from the end of the CRT. iii.Radiotherapy must have commenced no later than the end of Cycle 2 of chemotherapy. iv. Receipt of 3 cycles of platinum-based chemotherapy concurrent with RT will be permitted if the patient achieved disease control and Investigators judge no additional benefit will be expected with additional cycle of chemotherapy. 8.Patients must have achieved CR, PR, or SD and not have progressed following definitive, platinum-based, concurrent CRT. 9.Received a total dose of radiation of 60 to 66 Gy for standard QD radiation schedules or 45 Gy for hyperfractionated BID radiation schedules. Sites are encouraged to adhere to mean organ radiation dosing as follows: i. Mean lung dose ii.Heart V50 10.Tumor sample requirements: i. Provision of an archived tumor tissue block (or at least 15 newly cut unstained slides, where available) =3 years old, where such samples exist in a quantity sufficient to allow for analysis (refer to the Laboratory Manual for details) ii. A recent (=3 months) tumor biopsy (taken following completion of the most recent therapy) is an optional requirement, provided that a biopsy procedure is technically feasible, and the procedure is not associated with unacceptable clinical risk. 11. Adequate organ and marrow function independent of transfusion, infusion, or growth factor support for at least 14 days prior to screening, defined as below: i. Hemoglobin =9.0 g/dL ii. Absolute neutrophil count =1.5 × 109 /L
Exclusion criteria
Exclusion criteria: Patients are eligible to be included in the study only if none of the following exclusion criteria apply: Medical conditions 1. Mixed SCLC and NSCLC histology 2. Extensive-stage SCLC 3. Patients with Grade =2 pneumonitis from prior CRT 4. History of allogeneic organ transplantation 5. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, 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: 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 may be included but only after consultation with the Study Physician v. Patients with celiac disease controlled by diet alone 6. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, active ILD, serious chronic GI conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirements, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent 7. History of another primary malignancy except for: i. Malignancy treated with curative intent and with no known active disease =5 years before the first dose of IP and of low potential risk for recurrence ii. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease iii. Adequately treated carcinoma in situ without evidence of disease 8. History of leptomeningeal carcinomatosis 9. History of active primary immunodeficiency 10. 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 (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 and absence of HBsAg) are eligible. Patients positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA. 11. Any unresolved toxicity NCI Common Terminology Criteria for Adverse Events (CTCAE) Grade =2 from previous CRT with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria i. Patients with Grade =2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician. ii. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the Study Physician 12. Brain metastases or spinal cord compression. All patients will have an MRI (preferred) or CT, preferabl
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To assess the efficacy of durvalumab monotherapy as well as durvalumab in combination with tremelimumab therapy compared to placebo in terms of PFS •PFS using BICR assessments according to RECIST 1.1 To assess the efficacy of durvalumab in combination with tremelimumab therapy compared to placebo in terms of OS •OSTimepoint: During the Treatment period and Follow up period (Time frame-Approximately 4 years) | — |
Secondary
| Measure | Time frame |
|---|---|
| • To collect and store DNA from tissue and/or blood according to each country’s local and ethical procedures for future exploratory research into genes/genetic variation that may influence response (ie, distribution, safety, tolerability, and efficacy) to IPs and/or susceptibility to disease (optional)Timepoint: OS 4 YEARS;• To collect blood and tissue samples, or leverage residual samples, for analysis of peripheral and tumoral biomarkers • To investigate the relationship between a patient’s PD-L1 expression and spatial distribution within the tumor microenvironment and clinical outcomes with durvalumab monotherapy or durvalumab and tremelimumab combination therapy Timepoint: OS 4 YEARS;•To assess the efficacy of durvalumab and tremelimumab combination therapy compared to durvalumab monotherapy in terms of PFS, OS,and ORR •To assess disease-related symptoms and HRQoL in patients treated with durvalumab monotherapy or durvalumab and tremelimumab combination therapy compared to placebo using the EORTC, QLQ-C30 v3 and QLQ-LC13 •To assess the PK of durvalumab monotherapy and durvalumab and tremelimumab combination therapy Timepoint: OS 4 years;•To assess the efficacy of durvalumab monotherapy compared to placebo in terms of OS •To assess the efficacy of durvalumab monotherapy and durvalumab and tremelimumab combination therapy compared to placebo in terms of ORR, PFS18a, PFS24a, TTDM, OS24, OS36, and PFS2 Timepoint: os 4 years;•To assess the patients’ overall impression of the severity of their cancer symptoms using PGIS • To describe and evaluate health resource use associated with durvalumab monotherapy and durvalumab and tremelimumab combination therapy and underlying disease • To explore the impact of treatment and disease state on health state utility using the EQ-5D-5L Timepoint: OS 4 YEARS;•To investigate the immunogenicity of durvalumab monotherapy and durvalumab and tremelimumab combination therapy •To | — |
Countries
Argentina, Belgium, Canada, China, Czech Republic, Germany, India, Italy, Japan, Netherlands, Republic of Korea, Russian Federation, Spain, Taiwan, Turkey, United States of America, Viet Nam
Contacts
Public ContactMr Sandeep AV
AstraZeneca Pharma India Ltd.
Outcome results
None listed