A Phase II Clinical Trial Evaluating the Safety and Efficacy of Durvalumab (MEDI4736) as 1st Line Therapy in Advanced Non-small Cell Lung Cancer (NSCLC) Patients With Eastern Cooperative Oncology Group (ECOG) Performance Status of 2
Overview
- Phase
- Phase 2
- Intervention
- durvalumab
- Conditions
- Non-Small Cell Lung Cancer NSCLC
- Sponsor
- Academic Thoracic Oncology Medical Investigators Consortium
- Enrollment
- 47
- Locations
- 2
- Primary Endpoint
- Overall Survival (OS24)
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a single-arm phase II clinical trial evaluating the safety and efficacy of the PD-L1 inhibitor durvalumab as first-line therapy in 47 patients with advanced NSCLC and ECOG Performance Status 2 (PS2).
Detailed Description
Durvalumab will be supplied in glass vials containing 500 mg of liquid solution at a concentration of 50 mg/mL for intravenous (IV) administration. Durvalumab will be administered at 1500 mg (fixed dose) every 4 weeks until disease progression, death, unacceptable toxicity or withdrawal of consent for a maximum of 12 months of therapy.
Investigators
Liza Villaruz
Assistant Professor of Medicine, Division of Hematology Oncology
University of Pittsburgh
Eligibility Criteria
Inclusion Criteria
- •Written informed consent
- •Patients must have histologically or cytologically confirmed Stage IIIB or IV (American Joint Committee on Cancer, 7th edition; AJCC 7) non-small cell lung cancer.
- •Patients must have measurable disease.
- •Patients must have not have received any prior therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) for the treatment of stage IV NSCLC.
- •Age ≥ 18 years at time of study entry.
- •ECOG performance status of
- •Life expectancy of greater than 12 weeks.
- •Tissue available (archived or fresh tumor biopsy) for the PD-L1 assay.
- •Patients must have normal organ and marrow function as defined below:
- •Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L (\> 1500 per mm\^3)
Exclusion Criteria
- •Involvement in the planning and/or conduct of the study; previous enrollment in the present study.
- •Participation in another clinical study with an investigational product for cancer during the last 12 months.
- •Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab.
- •Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation and/or corticosteroids in excess of prednisone 10 mg/d or equivalent.
- •Sensitizing mutations in EGFR or rearrangements in ALK or ROS
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to durvalumab.
- •Mean QT interval corrected for heart rate (QTc) ≥ 470 ms.
- •Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids . Patients may be on systemic corticosteroids provided the dose does not exceed prednisone 10 mg/d or equivalent for 1 week prior to study drug administration.
- •Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
- •Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
Arms & Interventions
durvalumab
1500 mg of durvalumab will be administered intravenously (IV) on day 1 of every 28 day cycle.
Intervention: durvalumab
Outcomes
Primary Outcomes
Overall Survival (OS24)
Time Frame: At 24 months
Number of patients alive at 24 months post start of treatment.
Treatment-related Adverse Events ≥ Grade 3
Time Frame: Up to 30 months
Number of participants with ≥ Grade 3 adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.0 that are at least possibly related to study treatment.
Overall Survival (OS)
Time Frame: Up to 30 months
Median length of time from the start of treatment from start of treatment to death from any cause.
Overall Survival (OS12)
Time Frame: At 12 months
Number of patients alive at 12 months post start of treatment.
Secondary Outcomes
- Progression-Free Survival (PFS) by PD-L1 Expression at 12 Months(At 12 months)
- Overall Survival by PD-L1 Expression Status at 12 Months(At 12 months)
- Overall Response Rate (ORR) in Patients With PD-L1 Expression Status ≥50%(Up to 30 months)
- Progression-Free Survival (PFS)(Up to 30 months)
- Progression-Free Survival (PFS) at 12 Months(At 12 months)
- Progression-Free Survival (PFS) at 24 Months(At 24 months)
- Progression-Free Survival (PFS) by PD-L1 Expression Status at 24 Months(At 24 months)
- Overall Survival by PD-L1 Expression Status at 24 Months(At 24 months)
- Overall Response Rate (ORR)(Up to 30 months)
- Overall Response Rate (ORR) in Patients With PD-L1 Expression Status = 0%<PD-L1<50%.(Up to 30 months)
- FACT Lung Cancer Subscale (LCS)(At 12 months)
- Overall Response Rate (ORR) in Patients With PD-L1 Expression Status = 0(Up to 30 months)
- Health Related Quality of Life (HRQL) - FACT-G(At 12 months)