small-cell lung cancer
Conditions
Interventions
For the first 600 patients randomised:
Durvalumab + Tremelimumab combination therapy:
- Durvalumab (1500 mg IV) q4w in combination with tremelimumab (75 mg IV) q4w
for up to 4 doses/cycles each, fol
Sponsors
Astra Zeneca
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: - 18 years or older at the time of screening, - 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 - World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 at enrollment and randomization - Received an appropriate first line concurrent chemoradiotherapy regimen as defined below, unless after consultation with the global study medical team an alternative is acceptable * 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. * The chemotherapy regimen must contain platinum and IV etoposide, administered as per local standard-of-care regimens. * Received a total dose of radiation of 60 to 66 Gy over 6 weeks for standard QD radiation schedules or 45 Gy over 3 weeks for hyperfractionated BID radiation schedules. * Radiotherapy must have commenced no later than the end of Cycle 2 of chemotherapy. * Receipt of 3 cycles of platinum-based chemotherapy concurrent with RT will be permitted if the patient has achieved disease control and in the opinion of the Investigator, no additional benefit will be expected with additional cycle of chemotherapy., - Patients must have achieved CR, PR, or SD and not have progressed following definitive, platinum-based chemotherapy, concurrent with radiotherapy. - PCI may be delivered at the discretion of investigator and local standard of care and must be conducted after the end of cCRT and completed between 1 to 42 days to first dose of IP. - Tumor sample requirements: * Mandatory availability of tumor sample, which may include a core needle biopsy, newly cut unstained slides, or fine needle aspirate (FNA) cell block samples. * A newly acquired tumor biopsy is optional, provided that a biopsy procedure is technically feasible and the procedure is not associated with unacceptable clinical risk. - Adequate organ and marrow function independent of transfusion, infusion, or growth factor support for at least 14 days prior to obtaining screening labs, - Must have a life expectancy of at least 12 weeks, - Body weight >30 kg
Exclusion criteria
Exclusion criteria: - Mixed SCLC and NSCLC histology, - Extensive-stage SCLC, - Any history of Grade >=2 pneumonitis, - History of allogeneic organ transplantation, - 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: * Patients with vitiligo or alopecia * Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement * Any chronic skin condition that does not require systemic therapy * Patients without active disease in the last 5 years may be included but only after consultation with the Study Physician * Patients with celiac disease controlled by diet alone, - 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, - History of another primary malignancy except for: * 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 * Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease * Adequately treated carcinoma in situ without evidence of disease, - History of leptomeningeal carcinomatosis, - History of active primary immunodeficiency, - 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., - 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 * Patients with Grade >=2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician. * 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., - Brain metastases or spinal cord compression. All patients will have an MRI (preferred) or CT, preferably with IV contrast of the brain, prior to study entry., - Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) >=470 ms calculated from 3 ECGs (with
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - To assess the efficacy of durvalumab monotherapy compared to placebo in terms of PFS using BICR assessments according to RECIST 1.1 - To assess the efficacy of durvalumab monotherapy compared to placebo in terms of OS | — |
Secondary
| Measure | Time frame |
|---|---|
| - To assess the efficacy of durvalumab and tremelimumab combination therapy compared to placebo in terms of PFS and OS - To further assess the efficacy of durvalumab monotherapy and durvalumab and tremelimumab combination therapy compared to placebo in terms of ORR, PFS18, PFS24, TTDM, OS24, OS36, and PFS2 - 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 and 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 - To investigate the immunogenicity of durvalumab monotherapy and durvalumab and tremelimumab combination therapy - To investigate the relationship between PD-L1 expression and spatial distribution within the tumor microenvironment and clinical outcomes with durvalumab monotherapy or durvalumab and tremelimumab combination therapy | — |
Countries
Netherlands
Outcome results
None listed