We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03334617
Recruitment Status : Recruiting
First Posted : November 7, 2017
Last Update Posted : January 5, 2023
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE September 22, 2017
First Posted Date  ICMJE November 7, 2017
Last Update Posted Date January 5, 2023
Actual Study Start Date  ICMJE December 18, 2017
Estimated Primary Completion Date January 2, 2026   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 26, 2019)
Assessment of the efficacy of each treatment by evaluation of objective response rate [ Time Frame: 12 weeks ]
Endpoint based on Response Evaluation Criteria in Solid Tumours (RECIST 1.1) Objective response rate (ORR)
Original Primary Outcome Measures  ICMJE
 (submitted: November 3, 2017)
Assessment of the efficacy of each treatment by evaluation of objective response rate [ Time Frame: 12 weeks ]
Endpoint based on modified Response Evaluation Criteria in Solid Tumours (RECIST 1.1) Objective response rate (ORR)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 26, 2019)
  • 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. ]
    Assessment of the anti-tumour activity of each therapy.
  • 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. ]
    Assessment of the anti-tumour activity of each therapy.
  • 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 ]
    Assessment of the anti-tumour activity of each therapy.
  • 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. ]
    Assessment of the anti-tumour activity of each therapy.
  • Overall surival (OS) [ Time Frame: Through to study completion, up to 4.5 years. ]
    Assessment of the anti-tumour activity of each therapy.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 3, 2017)
  • Disease control rate (DCR) using modified RECIST 1.1 assessment for the anti-tumour activity of each therapy. [ Time Frame: Through to study completion, up to 3.5 years. ]
    Assessment of the anti-tumour activity of each therapy.
  • Best percentage change in tumour size using modified RECIST 1.1 assessment for the anti-tumour activity of each therapy [ Time Frame: Through to study completion, up to 3.5 years. ]
    Assessment of the anti-tumour activity of each therapy.
  • Duration of response (DoR) using modified RECIST 1.1 assessment for the anti-tumour activity of each therapy. [ Time Frame: Through to study completion, up to 3.5 years ]
    Assessment of the anti-tumour activity of each therapy.
  • Progression free survival (PFS) using modified RECIST 1.1 assessment for the anti-tumour activity of each therapy. [ Time Frame: Through to study completion, up to 3.5 years. ]
    Assessment of the anti-tumour activity of each therapy.
  • Overall surival (OS) [ Time Frame: Through to study completion, up to 4.5 years. ]
    Assessment of the anti-tumour activity of each therapy.
Current Other Pre-specified Outcome Measures
 (submitted: November 3, 2017)
Incidence of adverse events/serious adverse events to assess the safety and tolerability of each treatment [ Time Frame: Through to study completion, up to 3.5 years. ]
Physical examinations, laboratory findings, and vital signs AEs/SAEs collected throughout the study, from informed consent until the safety follow-up visit
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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).
Brief Summary 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model 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.

Within each module, there will be treatment cohorts.

Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-Small Cell Lung Cancer
Intervention  ICMJE
  • Drug: Durvalumab
    Durvalumab given IV at 1500 mg Q4W ±2 days
  • Drug: AZD9150
    AZD9150 given IV at 200mg every other day of a 1-week lead-in period followed by QW
  • Drug: AZD6738
    AZD6738 given orally at 240mg twice daily in Cycle 0 Days 1-7, followed by 7 days on treatment in each cycle between Days 22-28
  • Drug: Vistusertib
    Vistusertib (AZD2014) given orally at a dose of 125 mg BD on an intermittent dosing schedule of 2 days on, 5 days off
  • Drug: Olaparib
    Olaparib (AZD2281) given orally at 300 mg BD
  • Drug: Oleclumab
    Oleclumab given at dose level 1 for 2 cycles and then dose level 2 thereafter
  • Drug: trastuzumab deruxtecan
    Durvalumab given IV at 1120mg Q3W ±2 days for Module 6 only & trastuzumab deruxtecan given at 5.4 mg/kg via IV infusion Q3W ±2 days
  • Drug: cediranib
    cediranib given orally at 20 mg tablets on an intermittent schedule (5 days on, 2 days off), starting on C1D1
  • Drug: AZD6738 (ceralasertib)
    AZD6738 given at 240 mg twice daily for 14 days on treatment in each 28-day cycle, between Days 1 and 14.
  • Drug: AZD6738 (ceralasertib)
    AZD6738 given orally at 240mg twice daily for 14 days in each 28 day cycle (starting from Cycle 1) between Days 15-28
  • Drug: AZD6738 (ceralasertib) (240 mg or 160 mg)
    AZD6738 given orally at 240mg or 160mg twice daily in Cycle 0 Days 1-7, followed by 7 days on treatment in each cycle between Days 22-28
  • Drug: AZD6738 (ceralasertib) 7 days monotherapy
    AZD6738 given orally at 240 mg twice daily for 7 days on Day 1-7 in each 28 day cycle
Study Arms  ICMJE
  • Experimental: Durvalumab + olaparib
    Durvalumab given in combination with olaparib .
    Interventions:
    • Drug: Durvalumab
    • Drug: Olaparib
  • Experimental: Durvalumab + AZD9150
    Durvalumab given in combination with AZD9150.
    Interventions:
    • Drug: Durvalumab
    • Drug: AZD9150
  • Experimental: Durvalumab + AZD6738
    Durvalumab given in combination with AZD6738.
    Interventions:
    • Drug: Durvalumab
    • Drug: AZD6738
  • Experimental: Durvalumab + vistusertib
    Durvalumab given in combination with Vistusertib (AZD2014).
    Interventions:
    • Drug: Durvalumab
    • Drug: Vistusertib
  • Experimental: Durvalumab + Oleclumab
    Durvalumab given in combination with Oleclumab
    Interventions:
    • Drug: Durvalumab
    • Drug: Oleclumab
  • Experimental: durvalumab + trastuzumab deruxtecan
    durvalumab given in combination with trastuzumab deruxtecan (DS-8201a)
    Intervention: Drug: trastuzumab deruxtecan
  • Experimental: durvalumab + cediranib
    durvalumab given in combination with cediranib (AZD2171)
    Interventions:
    • Drug: Durvalumab
    • Drug: cediranib
  • Experimental: AZD6738 (ceralasertib) monotherapy
    AZD6738 (ceralasertib) given as monotherapy
    Intervention: Drug: AZD6738 (ceralasertib)
  • Experimental: durvalumab & AZD6738 (ceralasertib)
    durvalumab given in combination with AZD6738 (D15-D28)
    Interventions:
    • Drug: Durvalumab
    • Drug: AZD6738 (ceralasertib)
  • Experimental: durvalumab & AZD6738 (ceralasertib) (240 mg or 160 mg)
    durvalumab in combination with twice daily 160 mg or 240 mg AZD6738 (D22-D28)
    Intervention: Drug: AZD6738 (ceralasertib) (240 mg or 160 mg)
  • Experimental: AZD6738 (ceralasertib) 7 days monotherapy
    AZD6738 (ceralasertib) monotherapy on D1-7 of every 28 days
    Intervention: Drug: AZD6738 (ceralasertib) 7 days monotherapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 4, 2023)
570
Original Estimated Enrollment  ICMJE
 (submitted: November 3, 2017)
200
Estimated Study Completion Date  ICMJE January 2, 2026
Estimated Primary Completion Date January 2, 2026   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 at initial diagnosis 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 tuberculosis, 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, or history of severe hypersensitivity reactions to other monoclonal antibodies.
  • 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.
  • history of active primary immunodeficiency
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Listed Location Countries  ICMJE Austria,   Canada,   France,   Germany,   Israel,   Korea, Republic of,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03334617
Other Study ID Numbers  ICMJE D6185C00001
2017-002208-28 ( EudraCT Number )
138050 ( Registry Identifier: IND )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description:

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home
Current Responsible Party AstraZeneca
Original Responsible Party Same as current
Current Study Sponsor  ICMJE AstraZeneca
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: John Heymach, M.D, Ph.D The University of Texas MD Anderson Cancer Center
PRS Account AstraZeneca
Verification Date December 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP