Clinical trial NCT03509012: Immunotherapy in Combination With Chemoradiation in Patients With Advanced Solid Tumors
Official title: A Phase I Multicenter Study of Immunotherapy in Combination With Chemoradiation in Patients With Advanced Solid Tumors (CLOVER)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Carcinoma, Squamous Cell of Head and Neck
Carcinoma, Non-Small-Cell Lung
Small Cell Lung Carcinoma
Keywords: Durvalumab
Chemotherapy
Radiotherapy
HNSCC
NSCLC
SCLC
locally-advanced
limited stage
first line
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2018-04-26
Enrollment: 105
Sex: ALL
Minimum age (years): 18
Maximum age (years): 110
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: 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

Primary outcomes:
measure: Number of subjects with Dose Limiting Toxicities (DLTs)
timeFrame: From first dose of durvalumab until 28 days after completion of radiation therapy
measure: Number of subjects with Adverse Events (AEs)
timeFrame: From first dose of durvalumab up to 90 days after the last dose of study treatment
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: 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.
measure: Overall Survival (OS)
timeFrame: From first dose until death due to any cause through study completion, up to 4 years
measure: Objective response rate (ORR)
timeFrame: From first dose until disease progression, or the last evaluable assessment in the absence of progression, assessed up to 4 years.
measure: Best objective response (BoR)
timeFrame: From first dose until disease progression, or the last evaluable assessment in the absence of progression, assessed up to 4 years.
measure: Duration of response (DoR)
timeFrame: From first dose until disease progression, or death, in the absence of progression, assessed up to 4 years.
measure: Disease control rate (DCR)
timeFrame: From first dose until disease progression, at 18 weeks and 48 weeks.
measure: Disease-free survival (DFS)
timeFrame: From first dose until disease progression or death, in the absence of progression at 12, 18 and 24 months, assessed up to 4 years.
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Research Site
state: Arizona
city: Aurora
country: United States
facility: Research Site
state: Colorado
city: Houston
country: United States
facility: Research Site
state: Texas
city: Koto-ku
country: Japan
facility: Research Site
city: Sunto-gun
country: Japan
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Badalona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Málaga
country: Spain
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoyuan City
country: Taiwan
facility: Research Site
Study officials:
References: