Immunotherapy in Combination With Chemoradiation in Patients With Advanced Solid Tumors

Carcinoma, Non-Small-Cell Lung Clinical Trial

— CLOVER  

Official title:

A Phase I Multicenter Study of Immunotherapy in Combination With Chemoradiation in Patients With Advanced Solid Tumors (CLOVER)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03509012
• Other study ID #: D933BC00001
• Secondary ID: 2017-002242-77
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: May 2, 2018
• Est. completion date: December 31, 2024

Study information

• Verified date: May 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 105
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 110 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Carcinoma, Squamous Cell
• Carcinoma, Squamous Cell of Head and Neck
• Small Cell Lung Carcinoma
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• Durvalumab
IV (intravenous)
• Tremelimumab
IV
• Cisplatin (dose level 4)
IV
• Cisplatin (dose level 3)
IV
• Carboplatin (dose level 1)
IV
• Carboplatin (dose level 2)
IV
• Etoposide (dose level 1)
IV
• Etoposide (dose level 2)
IV
• Paclitaxel
IV
• Pemetrexed
IV

Radiation:
• External beam radiation (dose level 1)
radiation therapy
• External beam radiation (dose level 2)
radiation therapy
• External beam radiation (hyperfractionated)
radiation therapy

Drug:
• Cisplatin (dose level 1)
IV
• Cisplatin (dose level 2)
IV

Radiation:
• External beam radiation (standard)
radiation therapy

Locations

Country	Name	City	State
Japan	Research Site	Koto-ku
Japan	Research Site	Sunto-gun
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Spain	Research Site	Badalona
Spain	Research Site	Madrid
Spain	Research Site	Málaga
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taoyuan City
United States	Research Site	Aurora	Colorado
United States	Research Site	Houston	Texas
United States	Research Site	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Japan,  Korea, Republic of,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of subjects with Dose Limiting Toxicities (DLTs)		From first dose of durvalumab until 28 days after completion of radiation therapy
Primary	Number of subjects with Adverse Events (AEs)		From first dose of durvalumab up to 90 days after the last dose of study treatment
Secondary	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.
Secondary	Overall Survival (OS)		From first dose until death due to any cause through study completion, up to 4 years
Secondary	Objective response rate (ORR)	Number (%) of patients with an overall response of complete response (CR) or partial response (PR).	From first dose until disease progression, or the last evaluable assessment in the absence of progression, assessed up to 4 years.
Secondary	Best objective response (BoR)	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.	From first dose until disease progression, or the last evaluable assessment in the absence of progression, assessed up to 4 years.
Secondary	Duration of response (DoR)	Time from the date of first documented response until the first date of documented progression or death in the absence of disease progression.	From first dose until disease progression, or death, in the absence of progression, assessed up to 4 years.
Secondary	Disease control rate (DCR)		From first dose until disease progression, at 18 weeks and 48 weeks.
Secondary	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.