Durvalumab as First Line Therapy in Treating Patients with Stage IIIB-IV Non-small Cell Lung Cancer
- Written informed consent and any locally-required authorization (e.g., Health Insurance Portability and Accountability Act [HIPAA]) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
- 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, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
- 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; patients may have received prior adjuvant or neoadjuvant chemotherapy or chemotherapy given as part of a curative intent chemoradiotherapy approach for NSCLC, if the last administration of the prior regimens occurred at least 1 year prior to study entry
- ECOG performance status of 2
- Life expectancy of greater than 12 weeks
- Tissue available (archived or fresh tumor biopsy) for the PD-L1 assay
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (> 1500 per mm^3)
- Hemoglobin >= 9.0 g/dL
- Platelet count >= 100 x 10^9/L (>100,000 per mm^3)
- Serum bilirubin =< 1.5 x institutional upper limit of normal (ULN); this will not apply to subjects with confirmed Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be =< 5x ULN
- Serum creatinine clearance (CL) > 30 mL/min by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine clearance
- Female subjects must either be of non-reproductive potential (ie, post-menopausal by history: >= 60 years old and no menses for >= 1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) OR must have a negative serum pregnancy test upon study entry
- The effects of durvalumab on the developing human fetus are unknown. For this reason and because immunomodulatory agents are potentially teratogenic, sexually active women of child-bearing potential and men must agree to use adequate contraception (2 methods of effective contraception from screening) from screening, for the duration of study participation, and for at least 90 days following the last infusion of durvalumab; cessation of contraception after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
- Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site); 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
- Sensitizing mutations in EGFR or rearrangements in ALK or ROS1
- 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 calculated from 3 electrocardiograms (ECGs) using Frediricia’s correction
- Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid
- 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)
- History of primary immunodeficiency
- History of allogeneic organ transplant
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent
- Known history of previous clinical diagnosis of tuberculosis
- History of leptomeningeal carcinomatosis
- Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab
- Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
- Subjects with uncontrolled seizures
- Pregnant women are excluded from this study because durvalumab is associated with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with durvalumab, breastfeeding should be discontinued if the mother is treated with durvalumab
- Prior history of radiation pneumonitis
I. To estimate overall survival (OS) with durvalumab in advanced non-small cell lung cancer (NSCLC) patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS)2.
II. To estimate the safety of durvalumab in NSCLC patients with PS2 as determined by grade >= 3 treatment related adverse events.
I. To estimate the progression-free survival (PFS) with durvalumab in advanced NSCLC patients with PS2.
II. To estimate overall response rate (ORR).
III. To estimate the rate of 12-month survival (OS12).
IV. To estimate OS, PFS, and ORR by PD-L1 expression status.
V. To estimate the health related quality of life (HRQL) associated with durvalumab therapy in advanced NSCLC patients with PS 2.
Patients receive durvalumab intravenously (IV) over 60 minutes on day 1. Cycles repeat every 28 days for up to 12 months in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed for up for 12 months or until death, whichever occurs first.
Trial Phase Phase II
Trial Type Treatment
University of Pittsburgh Cancer Institute (UPCI)
Liza C. Villaruz
- Primary ID HCC 16-054
- Secondary IDs NCI-2017-01819
- Clinicaltrials.gov ID NCT02879617