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)

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

Tracking Information

• First Submitted Date: September 22, 2017
• First Posted Date: November 7, 2017
• Last Update Posted Date: September 25, 2019
• Actual Study Start Date: December 18, 2017
• Estimated Primary Completion Date: July 30, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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: Complete list of historical versions of study NCT03334617 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (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 (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: 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).
• 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: Interventional
• Study Phase: Phase 2

Study Design

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: Non-Small Cell Lung Cancer

Intervention

• 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

Study Arms

• 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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 19, 2018): 260
• Original Estimated Enrollment (submitted: November 3, 2017): 200
• Estimated Study Completion Date: July 30, 2021
• Estimated Primary Completion Date: July 30, 2021 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 99 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: Austria, Canada, France, Germany, Israel, Korea, Republic of, United States

Administrative Information

• NCT Number: NCT03334617
• Other Study ID Numbers: 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: Not Provided
• Responsible Party: AstraZeneca
• Study Sponsor: AstraZeneca
• Collaborators: Not Provided

Investigators

• Principal Investigator: John Heymach, M.D, Ph.D; The University of Texas MD Anderson Cancer Center

• PRS Account: AstraZeneca
• Verification Date: September 2019