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 |
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Recruitment Status :
Recruiting
First Posted : November 7, 2017
Last Update Posted : May 23, 2023
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Sponsor:
AstraZeneca
Information provided by (Responsible Party):
AstraZeneca
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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 Drug: trastuzumab deruxtecan Drug: cediranib Drug: AZD6738 (ceralasertib) Drug: AZD6738 (ceralasertib) (240 mg or 160 mg) Drug: AZD6738 (ceralasertib) 7 days monotherapy | Phase 2 |
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 : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 570 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 : | February 27, 2025 |
| Estimated Study Completion Date : | February 27, 2025 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Lung cancer
| Arm | Intervention/treatment |
|---|---|
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Experimental: Durvalumab + olaparib
Durvalumab given in combination with olaparib .
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Drug: Durvalumab
Durvalumab given IV at 1500 mg Q4W ±2 days Drug: Olaparib Olaparib (AZD2281) given orally at 300 mg BD |
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Experimental: Durvalumab + AZD9150
Durvalumab given in combination with AZD9150.
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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 |
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Experimental: Durvalumab + AZD6738
Durvalumab given in combination with AZD6738.
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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 |
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Experimental: Durvalumab + vistusertib
Durvalumab given in combination with Vistusertib (AZD2014).
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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 |
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Experimental: Durvalumab + Oleclumab
Durvalumab given in combination with Oleclumab
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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 |
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Experimental: durvalumab + trastuzumab deruxtecan
durvalumab given in combination with trastuzumab deruxtecan (DS-8201a)
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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 |
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Experimental: durvalumab + cediranib
durvalumab given in combination with cediranib (AZD2171)
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Drug: Durvalumab
Durvalumab given IV at 1500 mg Q4W ±2 days Drug: cediranib cediranib given orally at 20 mg tablets on an intermittent schedule (5 days on, 2 days off), starting on C1D1 |
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Experimental: AZD6738 (ceralasertib) monotherapy
AZD6738 (ceralasertib) given as monotherapy
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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. |
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Experimental: durvalumab & AZD6738 (ceralasertib)
durvalumab given in combination with AZD6738 (D15-D28)
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Drug: Durvalumab
Durvalumab given IV at 1500 mg Q4W ±2 days 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 |
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Experimental: durvalumab & AZD6738 (ceralasertib) (240 mg or 160 mg)
durvalumab in combination with twice daily 160 mg or 240 mg AZD6738 (D22-D28)
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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 |
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Experimental: AZD6738 (ceralasertib) 7 days monotherapy
AZD6738 (ceralasertib) monotherapy on D1-7 of every 28 days
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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 |
Primary Outcome Measures :
- 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 :
- 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.
Other Outcome Measures:
- 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
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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 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
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
| Contact: AstraZeneca Clinical Study Information Center | 1-877-240-9479 | information.center@astrazeneca.com |
Locations
Show 49 study locations
Sponsors and Collaborators
AstraZeneca
Investigators
| Principal Investigator: | John Heymach, M.D, Ph.D | The University of Texas MD Anderson Cancer Center |
| Responsible Party: | AstraZeneca |
| ClinicalTrials.gov Identifier: | NCT03334617 |
| Other Study ID Numbers: |
D6185C00001 138050 ( Registry Identifier: IND ) 2017-002208-28 ( EudraCT Number ) |
| First Posted: | November 7, 2017 Key Record Dates |
| Last Update Posted: | May 23, 2023 |
| Last Verified: | May 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| 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 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 |
| 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:
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Non-small cell lung cancer NSCLC anti-PD-1/PD-L1 umbrella study Durvalumab MEDI4736 Olaparib AZD2281 AZD9150 |
AZD6738 Vistusertib AZD2014 Oleclumab MEDI9447 Trastuzumab deruxtecan DS-8201a cediranib AZD2171 |
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 Trastuzumab Durvalumab |
Olaparib Cediranib Trastuzumab deruxtecan Antineoplastic Agents, Immunological Antineoplastic Agents Poly(ADP-ribose) Polymerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Protein Kinase Inhibitors Immunoconjugates Immunologic Factors Physiological Effects of Drugs |