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Phase II Umbrella Study of Novel Anti-cancer Agents in Patients With NSCLC Who Progressed on an Anti-PD-1/PD-L1 Containing Therapy.

NCT03334617

Description:

This is an open-label, multi-centre, umbrella Phase II study in patients with metastatic NSCLC who have progressed on an anti-PD-1/PD-L1 containing therapy. This study is modular in design, allowing initial assessment of the efficacy, safety, and tolerability of multiple treatment arms.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase II Umbrella Study of Novel Anti-cancer Agents in Patients With NSCLC Who Progressed on an Anti-PD-1/PD-L1 Containing Therapy.
  • Official Title: An Open-Label, Multi-Drug, Biomarker-Directed, Multi-Centre Phase II Umbrella Study in Patients With Non-Small Cell Lung Cancer, Who Progressed on an Anti-PD-1/PD-L1 Containing Therapy (HUDSON).

Clinical Trial IDs

  • ORG STUDY ID: D6185C00001
  • SECONDARY ID: 2017-002208-28
  • SECONDARY ID: 138050
  • NCT ID: NCT03334617

Conditions

  • Non-Small Cell Lung Cancer

Interventions

DrugSynonymsArms
DurvalumabDurvalumab + olaparib
AZD9150Durvalumab + AZD9150
AZD6738Durvalumab + AZD6738
VistusertibDurvalumab + vistusertib
OlaparibDurvalumab + olaparib
OleclumabDurvalumab + Oleclumab

Purpose

This is an open-label, multi-centre, umbrella Phase II study in patients with metastatic NSCLC who have progressed on an anti-PD-1/PD-L1 containing therapy. This study is modular in design, allowing initial assessment of the efficacy, safety, and tolerability of multiple treatment arms.

Detailed Description

      This is an open-label, multi-centre, umbrella Phase II study in patients with metastatic
      non-small cell lung cancer (NSCLC) who have progressed on an anti-programmed cell
      death-1/anti-programmed cell death ligand 1 (anti-PD-1/PD-L1) containing therapy. This study
      is modular in design, consisting of a number of treatment cohorts, allowing evaluation of the
      efficacy, safety, and tolerability of multiple treatment arms. There is currently no
      established therapy for patients who have received immune checkpoint inhibitors and
      platinum-doublet therapies, and novel treatments are urgently needed.

      This protocol has a modular design, with the potential for future treatment arms to be added
      via protocol amendment.
    

Trial Arms

NameTypeDescriptionInterventions
Durvalumab + olaparibExperimentalDurvalumab given in combination with olaparib .
  • Durvalumab
  • Olaparib
Durvalumab + AZD9150ExperimentalDurvalumab given in combination with AZD9150.
  • Durvalumab
  • AZD9150
Durvalumab + AZD6738ExperimentalDurvalumab given in combination with AZD6738.
  • Durvalumab
  • AZD6738
Durvalumab + vistusertibExperimentalDurvalumab given in combination with Vistusertib (AZD2014).
  • Durvalumab
  • Vistusertib
Durvalumab + OleclumabExperimentalDurvalumab given in combination with Oleclumab
  • Durvalumab
  • Oleclumab

Eligibility Criteria

        Inclusion criteria:

          -  At least 18 years of age at the time of signing the informed consent form.

          -  Patient must have histologically or cytologically confirmed metastatic or locally
             advanced and recurrent NSCLC which is progressing.

          -  Patients eligible for second- or later-line therapy, who must have received an
             antiPD1/PD-L1 containing therapy and a platinum-doublet regimen for locally advanced
             or metastatic NSCLC either separately or in combination. Prior durvalumab is
             acceptable. The patient must have had disease progression on a prior line of
             antiPD1/PD-L1 therapy.

          -  ECOG/WHO performance status of 0 to 1, and a minimum life expectancy of 12 weeks.

          -  Patient must have at least 1 lesion that can be accurately measured. A previously
             irradiated lesion can be considered a target lesion if the lesion has clearly
             progressed.

          -  Evidence of post-menopausal status or negative urinary or serum pregnancy test for
             female pre-menopausal patients.

        Exclusion Criteria:

          -  Patients whose tumour samples have targetable alterations in EGFR and/or ALK are
             excluded. In addition, patients whose tumour samples are known to have targetable
             alterations in ROS1, BRAF, MET or RET, are to be excluded.

          -  Active or prior documented autoimmune or inflammatory disorders.

          -  Active infection including hepatitis B (known positive HBV surface antigen [HBsAg]
             result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies).

          -  Female patients who are pregnant or breastfeeding, or male or female patients of
             reproductive potential who are not willing to employ effective birth control.

          -  Known allergy or hypersensitivity to any of the study drugs or any of the study drug
             excipients.

          -  Patient has spinal cord compression or symptomatic brain metastases.

          -  Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer
             treatment. Patients may receive treatment with bisphosphonates or receptor activator
             of nuclear factor kappa-Β ligand (RANKL) inhibitors for the treatment of bone
             metastases.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Assessment of the efficacy of each treatment by evaluation of objective response rate
Time Frame:12 weeks
Safety Issue:
Description:Endpoint based on Response Evaluation Criteria in Solid Tumours (RECIST 1.1) Objective response rate (ORR)

Secondary Outcome Measures

Measure:Disease control rate (DCR) using RECIST 1.1 assessment for the anti-tumour activity of each therapy.
Time Frame:Through to study completion, up to 3.5 years.
Safety Issue:
Description:Assessment of the anti-tumour activity of each therapy.
Measure:Best percentage change in tumour size using RECIST 1.1 assessment for the anti-tumour activity of each therapy
Time Frame:Through to study completion, up to 3.5 years.
Safety Issue:
Description:Assessment of the anti-tumour activity of each therapy.
Measure:Duration of response (DoR) using RECIST 1.1 assessment for the anti-tumour activity of each therapy.
Time Frame:Through to study completion, up to 3.5 years
Safety Issue:
Description:Assessment of the anti-tumour activity of each therapy.
Measure:Progression free survival (PFS) using RECIST 1.1 assessment for the anti-tumour activity of each therapy.
Time Frame:Through to study completion, up to 3.5 years.
Safety Issue:
Description:Assessment of the anti-tumour activity of each therapy.
Measure:Overall surival (OS)
Time Frame:Through to study completion, up to 4.5 years.
Safety Issue:
Description:Assessment of the anti-tumour activity of each therapy.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

  • Non-small cell lung cancer
  • NSCLC
  • anti-PD-1/PD-L1
  • umbrella study
  • Durvalumab
  • MEDI4736
  • Olaparib
  • AZD2281
  • AZD9150
  • AZD6738
  • Vistusertib
  • AZD2014
  • Oleclumab
  • MEDI9447

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