Astra Zeneca (Immuno Stereotactic Ablative Body Radiotherapy) ISABR Study: Randomized Phase I/II Study of Stereotactic Body Radiotherapy
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Registration Number
- NCT03148327
- Lead Sponsor
- Jonsson Comprehensive Cancer Center
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Active, not recruiting
- Sex
- All
- Target Recruitment
- 18
Inclusion Criteria:<br><br>For inclusion in the study subjects must fulfill all of the following criteria:<br><br> 1. Written informed consent obtained from the patient/legal representative prior to<br> performing any protocol-related procedures, including screening evaluation.<br><br> 2. Newly diagnosed, untreated, biopsy proven non-small cell lung cancer.<br><br> 3. Medically inoperable or patient refusal to surgery as defined by any single of the<br> following criteria: a. Determined unfit for surgery by thoracic surgeon or radiation<br> oncologist as documented in the medical record b. Pulmonary function test (PFTS)<br> showing Forced Expiratory Volume in the first second (FEV1) = 1.2 L or diffusing<br> Lung Capacity (DLC) <60%, c. Poor exercise tolerance or failed pre-operative cardiac<br> work-up, d. Patient refusal to undergo definitive surgery as documented in clinical<br> note by a surgeon, pulmonologist, medical oncologist, or radiation oncologist.<br><br> 4. Clinically stage I disease by American Joint Committee on Cancer (AJCC) 7th edition.<br> (N0, M0, T stages T1-T2a) or patients with stage T2bN0M0 (clinical stage IIA)<br> disease who are medically unfit for standard of care chemotherapy as documented by a<br> medical oncologist or radiation oncologist, or who refuse standard of care<br> chemotherapy as documented by a medical oncologist or radiation oncologist.<br><br> 5. Age > 18 years at time of study entry.<br><br> 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1.<br><br> 7. Adequate normal organ and marrow function as defined below:<br><br> - Haemoglobin = 9.0 g/dL.<br><br> - Absolute neutrophil count (ANC) = 1.5 x 109/L (> 1500 per mm3).<br><br> - Platelet count = 100 x 109/L (>100,000 per mm3).<br><br> - Serum bilirubin = 1.5 x institutional upper limit of normal (ULN). <<This will<br> not apply to subjects with confirmed Gilbert's syndrome (persistent or<br> recurrent hyperbilirubinemia that is predominantly unconjugated in the absence<br> of hemolysis or hepatic pathology), who will be allowed only in consultation<br> with their physician.>><br><br> - aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase<br> (SGOT)/ alanine aminotransferase (ALT) serum glutamic pyruvic transaminase<br> (SGPT) = 2.5 x institutional upper limit of normal unless liver metastases are<br> present, in which case it must be = 5x ULN.<br><br> - Serum creatinine creatinine clearance (CL) >40 mL/min by the Cockcroft-Gault<br> formula (Cockcroft and<br><br> Gault 1976) or by 24-hour urine collection for determination of creatinine<br> clearance:<br><br> Males:<br><br> Creatinine CL (mL/min)<br><br> = Weight (kg) x (140 - Age) . 72 x serum creatinine (mg/dL)<br><br> Females:<br><br> Creatinine CL (mL/min)<br><br> = Weight (kg) x (140 - Age) x 0.85 72 x serum creatinine (mg/dL)<br><br> 8. Female subjects must either be of non-reproductive potential (i.e. post-menopausal<br> by history: =60 years old and no menses for =1 year without an alternative medical<br> cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR<br> history of bilateral oophorectomy) or must have a negative serum pregnancy test upon<br> study entry.<br><br> 9. Subject is willing and able to comply with the protocol for the duration of the<br> study including undergoing treatment and scheduled visits and examinations including<br> follow up.<br><br>Exclusion Criteria:<br><br> 1. ECOG Performance status >1.<br><br> 2. Patients with metastatic or node positive NSCLC.<br><br> 3. Patients with prior radiation therapy to the same bronchopulmonary segment.<br><br> 4. History of automimmune disease including myasthenia gravis, myositis, autoimmune<br> hepatitis, systemic lupus erythematous, rheumatoid arthritis, inflammatory bowel<br> disease (e.g., Crohn's disease, ulcerative colitis), vascular thrombosis associated<br> with antiphospholipid syndrome, Wegner's granulomatosis, Sjogren's syndrome,<br> Guillain-Barre syndrome, multiple sclerosis, or glomerulonephritis.<br><br> a. However, patients with type 1 diabetes mellitus, vitiligo, alopecia,<br> hypothyroidism requiring hormone replacement, Graves disease, or skin disorders not<br> requiring systemic treatment are permitted to enroll.<br><br> 5. Patients with history of idiopathic pulmonary fibrosis, idiopathic pneumonitis, drug<br> induced pneumonitis, or evidence of active pneumonitis on screening chest CT scan.<br><br> 6. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca<br> staff and/or staff at the study site).<br><br> 7. Participation in another clinical study with an investigational product during the<br> last 6 months.<br><br> 8. Any previous treatment with a Programmed Death-1 (PD1) or Programmed Death-Ligand<br> 1(PD-L1) inhibitor, including durvalumab, and therapeutic anticancer vaccine.<br><br> 9. History of another primary malignancy except for:<br><br> 1. Malignancy treated with curative intent and with no known active disease =5<br> years before the first dose of study drug and of low potential risk for<br> recurrence.<br><br> 2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence<br> of disease.<br><br> 3. Adequately treated carcinoma in situ without evidence of disease e.g., cervical<br> cancer in situ.<br><br> 10. Mean QT interval corrected for heart rate (QTc) =470 ms calculated from 3<br> electrocardiograms (ECGs) using Frediricia's Correction.<br><br> 11. Current or prior use of immunosuppressive medication within 28 days before the first<br> dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or<br> systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day<br> of prednisone, or an equivalent corticosteroid.<br><br> 12. Any unresolved = Grade 2 pulmonary toxicity from previous anti-cancer therapy.<br><br> 13. Any prior Grade =3 immune-related adverse event (irAE) while receiving any previous<br> immunotherapy agent, or any unresolved irAE >Grade 1.<br><br> 14. History of primary immunodeficiency.<br><br> 15. History of allogeneic organ transplant.<br><br> 16. History of hypersensitivity to durvalumab or any excipient.<br><br> 17. Uncontrolled intercurrent illness including, but not limited to, ongoing or active<br> infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable<br> angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis,<br> active bleeding diatheses including any subject known to have evidence of acute or<br> chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or<br> psychiatric illness/social situations that would limit compliance with study<br> requirements or compromise the ability of the subject to give written informed<br> consent.<br><br> 18. Known history of previous clinical diagnosis of tuberculosis.<br><br> 19. History of leptomeningeal carcinomatosis.<br><br> 20. Receipt of live attenuated vaccination within 30 days prior to study entry or within<br> 30 days of receiving durvalumab.<br><br> 21. Female subjects who are pregnant, breast-feeding or male or female patients of<br> reproductive potential who are not employing an effective method of birth control.<br><br> 22. Any condition that, in the opinion of the investigator, would interfere with<br> evaluation of study treatment or interpretation of patient safety or
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Phase I: The number and severity of study participants' treatment-related adverse events as assessed by CTCAE v4.0.;Phase II: Median Progression-Free Survival
- Secondary Outcome Measures
Name Time Method Overall survival;Primary Tumor Control;Intralobar recurrence rates;mediastinal recurrences;hilar and mediastinal recurrences;rate of distant recurrences;rates of grade 3 or higher non-hematological toxicities