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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. (HUDSON)

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ClinicalTrials.gov Identifier: NCT03334617
Recruitment Status : Recruiting
First Posted : November 7, 2017
Last Update Posted : September 25, 2019
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

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.

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Drug: Durvalumab Drug: AZD9150 Drug: AZD6738 Drug: Vistusertib Drug: Olaparib Drug: Oleclumab Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 260 participants
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
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).
Actual Study Start Date : December 18, 2017
Estimated Primary Completion Date : July 30, 2021
Estimated Study Completion Date : July 30, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Durvalumab + olaparib
Durvalumab given in combination with olaparib .
Drug: Durvalumab
Durvalumab given IV at 1500 mg Q4W ±2 days

Drug: Olaparib
Olaparib (AZD2281) given orally at 300 mg BD

Experimental: Durvalumab + AZD9150
Durvalumab given in combination with AZD9150.
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

Experimental: Durvalumab + AZD6738
Durvalumab given in combination with AZD6738.
Drug: Durvalumab
Durvalumab given IV at 1500 mg Q4W ±2 days

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

Experimental: Durvalumab + vistusertib
Durvalumab given in combination with Vistusertib (AZD2014).
Drug: Durvalumab
Durvalumab given IV at 1500 mg Q4W ±2 days

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

Experimental: Durvalumab + Oleclumab
Durvalumab given in combination with Oleclumab
Drug: Durvalumab
Durvalumab given IV at 1500 mg Q4W ±2 days

Drug: Oleclumab
Oleclumab given at dose level 1 for 2 cycles and then dose level 2 thereafter




Primary Outcome Measures :
  1. 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)



Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. Overall surival (OS) [ Time Frame: Through to study completion, up to 4.5 years. ]
    Assessment of the anti-tumour activity of each therapy.


Other Outcome Measures:
  1. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03334617


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Contact: Cancer Study Locator 1-877-400-4656 AstraZeneca@emergingmed.com

  Show 40 Study Locations
Sponsors and Collaborators
AstraZeneca
Investigators
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Principal Investigator: John Heymach, M.D, Ph.D The University of Texas MD Anderson Cancer Center

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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03334617     History of Changes
Other Study ID Numbers: D6185C00001
2017-002208-28 ( EudraCT Number )
138050 ( Registry Identifier: IND )
First Posted: November 7, 2017    Key Record Dates
Last Update Posted: September 25, 2019
Last Verified: September 2019

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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
Keywords provided by AstraZeneca:
Non-small cell lung cancer
NSCLC
anti-PD-1/PD-L1
umbrella study
Durvalumab
MEDI4736
Olaparib
AZD2281
AZD9150
AZD6738
Vistusertib
AZD2014
Oleclumab
MEDI9447
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Durvalumab
Olaparib
Antibodies, Monoclonal
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action