A Phase Ib study of Concurrent Neoadjuvant Chemoradiotherapy plus Durvalumab (MEDI4736) in Potentially Resectable Stage II/IIIa NSCLC
- Conditions
- Neoplasms
Recruitment & Eligibility
- Status
- Active, not recruiting
- Sex
- All
- Target Recruitment
- 30
1. Histologically confirmed NSCLC
2. Clinical stage III (including N2 stage and potential candidate for resection), to enroll for the subject will be determined by feasibility and the possibility of resection, whether or not.
3. Written informed consent and any locally-required authorization (IRB) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
4. Age = 20 years at time of study entry
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
6. Adequate normal organ and marrow function as defined below:
-Haemoglobin = 9.0 g/dL
-Absolute neutrophil count (ANC) = 1,500µL
-Platelet count = 100,000µL
-Serum bilirubin = 1.5 x institutional upper limit of normal (ULN). >
-AST (SGOT)/ALT (SGPT) = 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be = 5x ULN
-Serum creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:
--Males:
Creatinine CL (mL/min) = Weight (kg) x (140 – Age)
72 x serum creatinine (mg/dL)
--Females:
Creatinine CL (mL/min) = Weight (kg) x (140 – Age) x 0.85
72 x serum creatinine (mg/dL)
6. Life expectancy of 6 months
8. Female subjects must either be of non-reproductive potential (ie, post-menopausal by history: =50 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.
9. 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.
1. Patients with metastatic disease or clinical N3 lymph node
2. Patients who participated another clinical study with an investigational product during the last 60 months
3. Involvement in the planning and/or conduct of the study previous enrollment in the present study
4. Any previous treatment (chemotherapy, radiotherapy or surgery) to current disease - NSCLC
5. Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
6. History of leptomeningeal carcinomatosis
7. Brain metastases or spinal cord compression. Subjects with suspected brain metastases at screening should have an MRI (preferred) or CT each preferably with IV contrast of the brain prior to study entry
8. Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) = 36months prior to the first dose of study drug
9. Mean QT interval corrected for heart rate (QTc) =470 ms calculated from 3 electrocardiograms (ECGs) using Frediricia’s Correction
10. Current or prior use of immunosuppressive medication within 14days (use 28 days if combining durvalumab with a novel agent) 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. The following are exceptions to this criterion:
-Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra articular injection)
-Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
-Steroids as premedication for hypersensitivity reactions (eg, chemotherapy, CT scan premedication)
11. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (eg, hormone replacement therapy) is acceptable.
12. Patients who underwent major surgery (as determined by the investigator) within 28 days before taking the first dose of investigational product
13. History of allogeneic organ transplant
14. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
-Subjects with vitiligo or alopecia
-Subjects with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement
-Any chronic skin condition that does not require systemic therapy
-Subjects without active disease in the last 5 years may be included but only after consultation with the study physician
-Subjects with celiac disease controlled by diet alone
15. 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 re
Study & Design
- Study Type
- Interventional Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method pathologic complete response (pCR) rate
- Secondary Outcome Measures
Name Time Method DFS (disease free survival);clinical and pathologic down staging rate;no cancer cells seen microscopically at the resection margin (R0 rate);OS (overall survival);Objective response rate (ORR)