Clinical trial NCT03334617: 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).
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Non-Small Cell Lung Cancer
Keywords: 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
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2017-11-07
Enrollment: 527
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: Assessment of the efficacy of each treatment by evaluation of objective response rate
timeFrame: 12 weeks
Secondary outcomes:
measure: Disease control rate (DCR) using RECIST 1.1 assessment for the anti-tumour activity of each therapy.
timeFrame: Through to study completion, up to 3.5 years.
measure: Best percentage change in tumour size using RECIST 1.1 assessment for the anti-tumour activity of each therapy
timeFrame: Through to study completion, up to 3.5 years.
measure: Duration of response (DoR) using RECIST 1.1 assessment for the anti-tumour activity of each therapy.
timeFrame: Through to study completion, up to 3.5 years
measure: Progression free survival (PFS) using RECIST 1.1 assessment for the anti-tumour activity of each therapy.
timeFrame: Through to study completion, up to 3.5 years.
measure: Overall surival (OS)
timeFrame: Through to study completion, up to 4.5 years.
Other outcomes:
measure: Incidence of adverse events/serious adverse events to assess the safety and tolerability of each treatment
timeFrame: Through to study completion, up to 3.5 years.
Locations:
city: Duarte
country: United States
facility: Research Site
state: California
city: Fullerton
country: United States
facility: Research Site
state: California
city: La Jolla
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Washington
country: United States
facility: Research Site
state: District of Columbia
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: New York
country: United States
facility: Research Site
state: New York
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Research Site
state: Pennsylvania
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Houston
country: United States
facility: Research Site
state: Texas
city: Fairfax
country: United States
facility: Research Site
state: Virginia
city: Innsbruck
country: Austria
facility: Research Site
city: Salzburg
country: Austria
facility: Research Site
city: Wien
country: Austria
facility: Research Site
city: Wien
country: Austria
facility: Research Site
city: Edmonton
country: Canada
facility: Research Site
state: Alberta
city: Brampton
country: Canada
facility: Research Site
state: Ontario
city: Ottawa
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Bordeaux
country: France
facility: Research Site
city: Nantes Cedex 1
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Villejuif
country: France
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Esslingen a.N.
country: Germany
facility: Research Site
city: Grosshansdorf
country: Germany
facility: Research Site
city: Heidelberg
country: Germany
facility: Research Site
city: Köln
country: Germany
facility: Research Site
city: Haifa
country: Israel
facility: Research Site
city: Kfar Saba
country: Israel
facility: Research Site
city: Petah Tikva
country: Israel
facility: Research Site
city: Ramat Gan
country: Israel
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
Study officials:
affiliation: The University of Texas MD Anderson Cancer Center
name: John Heymach, M.D, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: