Clinical Trials /

Immunotherapy in Combination With Chemoradiation in Patients With Advanced Solid Tumors

NCT03509012

Description:

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

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: D933BC00001
  • NCT ID: NCT03509012

Conditions

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

Interventions

DrugSynonymsArms
DurvalumabMEDI4736HNSCC Arm 1
TremelimumabSCLC Arm 3
Cisplatin (dose level 4)HNSCC Arm 1
Cisplatin (dose level 3)SCLC Arm 1
Carboplatin (dose level 1)NSCLC Arm 2
Carboplatin (dose level 2)NSCLC Arm 3
Etoposide (dose level 1)NSCLC Arm 1
Etoposide (dose level 2)SCLC Arm 1
PaclitaxelNSCLC Arm 2
PemetrexedNSCLC Arm 3
Cisplatin (dose level 1)NSCLC Arm 1
Cisplatin (dose level 2)NSCLC Arm 3

Purpose

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).
    

Trial Arms

NameTypeDescriptionInterventions
HNSCC Arm 1ExperimentalDurvalumab + cisplatin with radiation in patients with locally advanced squamous cell carcinoma of the head and neck (HNSCC)
  • Durvalumab
  • Cisplatin (dose level 4)
NSCLC Arm 1ExperimentalDurvalumab + cisplatin and etoposide with radiation in patients with locally advanced, unresectable (Stage III) non-small-cell lung cancer (NSCLC)
  • Durvalumab
  • Etoposide (dose level 1)
  • Cisplatin (dose level 1)
NSCLC Arm 2ExperimentalDurvalumab + carboplatin and paclitaxel with radiation in patients with locally advanced, unresectable (Stage III) non-small-cell lung cancer (NSCLC)
  • Durvalumab
  • Carboplatin (dose level 1)
  • Paclitaxel
NSCLC Arm 3ExperimentalInvestigator's choice of carboplatin and pemetrexed OR cisplatin and pemetrexed
  • Durvalumab
  • Carboplatin (dose level 2)
  • Pemetrexed
  • Cisplatin (dose level 2)
SCLC Arm 1ExperimentalPatients should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin
  • Durvalumab
  • Cisplatin (dose level 3)
  • Carboplatin (dose level 2)
  • Etoposide (dose level 2)
SCLC Arm 2ExperimentalPatients with limited-stage small-cell lung cancer (SCLC) should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin
  • Durvalumab
  • Cisplatin (dose level 3)
  • Carboplatin (dose level 2)
  • Etoposide (dose level 2)
SCLC Arm 3ExperimentalPatients should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin. Note: Arm 3 will only be opened if the regimen in SCLC Arm 1 is safe and tolerable.
  • Durvalumab
  • Tremelimumab
  • Cisplatin (dose level 3)
  • Carboplatin (dose level 2)
  • Etoposide (dose level 2)
SCLC Arm 4ExperimentalPatients should start with cisplatin, but if cisplatin is not tolerated, they have the option to switch to carboplatin Note: Arm 4 will only be opened if the regimen in SCLC Arm 2 is safe and tolerable.
  • Durvalumab
  • Tremelimumab
  • Cisplatin (dose level 3)
  • Carboplatin (dose level 2)
  • Etoposide (dose level 2)

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
      
Maximum Eligible Age:110 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of subjects with Dose Limiting Toxicities (DLTs)
Time Frame:From first dose of durvalumab until 28 days after completion of radiation therapy
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Progression-free survival (PFS)
Time Frame: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.
Safety Issue:
Description:
Measure:Overall Survival (OS)
Time Frame:From first dose until death due to any cause through study completion, up to 4 years
Safety Issue:
Description:
Measure:Objective response rate (ORR)
Time Frame:From first dose until disease progression, or the last evaluable assessment in the absence of progression, assessed up to 4 years.
Safety Issue:
Description:Number (%) of patients with an overall response of complete response (CR) or partial response (PR).
Measure:Best objective response (BoR)
Time Frame:From first dose until disease progression, or the last evaluable assessment in the absence of progression, assessed up to 4 years.
Safety Issue:
Description: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.
Measure:Duration of response (DoR)
Time Frame:From first dose until disease progression, or death, in the absence of progression, assessed up to 4 years.
Safety Issue:
Description:Time from the date of first documented response until the first date of documented progression or death in the absence of disease progression.
Measure:Disease control rate (DCR)
Time Frame:From first dose until disease progression, at 18 weeks and 48 weeks.
Safety Issue:
Description:
Measure:Disease-free survival (DFS)
Time Frame:From first dose until disease progression or death, in the absence of progression at 12, 18 and 24 months, assessed up to 4 years.
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

  • Durvalumab
  • Chemotherapy
  • Radiotherapy
  • HNSCC
  • NSCLC
  • SCLC
  • locally-advanced
  • limited stage
  • first line

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