Carcinoma, Non-Small-Cell Lung, Carcinoma, Squamous Cell of Head and Neck, Small Cell Lung Carcinoma
Conditions
Keywords
Durvalumab, Chemotherapy, Radiotherapy, HNSCC, NSCLC, SCLC, locally-advanced, limited stage, first line
Brief summary
This is an open-label, multicenter, phase I study to evaluate the safety and tolerability of durvalumab ± tremelimumab in combination with chemoradiation in patients with advanced solid tumors
Detailed description
This study will initially treat up to approximately 300 patients with advanced solid tumors at approximately 30 sites, worldwide. The study will be composed of a dose-limiting toxicity (DLT) assessment phase (Part A) and an expansion phase (Part B).
Interventions
DRUGDurvalumab
IV (intravenous)
DRUGTremelimumab
IV
DRUGCisplatin (dose level 4)
IV
DRUGCisplatin (dose level 3)
IV
DRUGCarboplatin (dose level 1)
IV
DRUGCarboplatin (dose level 2)
IV
DRUGEtoposide (dose level 1)
IV
DRUGEtoposide (dose level 2)
IV
DRUGPaclitaxel
IV
DRUGPemetrexed
IV
RADIATIONExternal beam radiation (dose level 1)
radiation therapy
RADIATIONExternal beam radiation (dose level 2)
radiation therapy
RADIATIONExternal beam radiation (hyperfractionated)
radiation therapy
DRUGCisplatin (dose level 1)
IV
DRUGCisplatin (dose level 2)
IV
RADIATIONExternal beam radiation (standard)
radiation therapy
Sponsors
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 110 Years
Healthy volunteers
No
Inclusion criteria
* World Health Organization (WHO)/ECOG performance status of 0 or 1 * Body weight \>30 kg at enrollment and treatment assignment * At least 1 measurable lesion, not previously irradiated * No prior exposure to immune-mediated therapy (including therapeutic anticancer vaccines) * For patients with oropharyngeal HNSCC HPV status has to be known
Exclusion criteria
* Patients with simultaneous primary malignancies or bilateral tumors * Active or prior documented autoimmune or inflammatory disorders * Brain metastases or spinal cord compression * Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus (HIV; positive HIV 1/2 antibodies) * Has a paraneoplastic syndrome (PNS) of autoimmune nature * HNSCC cohort: Head and neck cancer that does not include unresectable, locally advanced cancer of oral cavity, larynx, oropharynx or hypopharynx. HNSCC of unknown primary are also excluded * NSCLC and SCLC cohort: Mixed SCLC and NSCLC histology * SCLC cohort: Extensive-stage SCLC
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of subjects with Dose Limiting Toxicities (DLTs) | From first dose of durvalumab until 28 days after completion of radiation therapy |
| Number of subjects with Adverse Events (AEs) | From first dose of durvalumab up to 90 days after the last dose of study treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | From first dose until disease progression, or the last evaluable assessment in the absence of progression, assessed up to 4 years. | Number (%) of patients with an overall response of complete response (CR) or partial response (PR). |
| Best objective response (BoR) | From first dose until disease progression, or the last evaluable assessment in the absence of progression, assessed up to 4 years. | The best response based on the overall visit responses from each RECIST 1.1 assessment or the last evaluable assessment in the absence of RECIST 1.1 progression. |
| Progression-free survival (PFS) | From first dose until the date of objective disease progression or death, in the absence of progression at 12, 18 and 24 months, up to 4 years. | — |
| Disease control rate (DCR) | From first dose until disease progression, at 18 weeks and 48 weeks. | — |
| Disease-free survival (DFS) | From first dose until disease progression or death, in the absence of progression at 12, 18 and 24 months, assessed up to 4 years. | — |
| Duration of response (DoR) | From first dose until disease progression, or death, in the absence of progression, assessed up to 4 years. | Time from the date of first documented response until the first date of documented progression or death in the absence of disease progression. |
| Overall Survival (OS) | From first dose until death due to any cause through study completion, up to 4 years | — |
Countries
Japan, South Korea, Spain, Taiwan, United States
Outcome results
None listed