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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03148327




Registration number
NCT03148327
Ethics application status
Date submitted
3/05/2017
Date registered
11/05/2017

Titles & IDs
Public title
Astra Zeneca (Immuno Stereotactic Ablative Body Radiotherapy) ISABR Study: Randomized Phase I/II Study of Stereotactic Body Radiotherapy
Scientific title
Randomized Phase I/II Study of Ablative Radiotherapy +/- MEDI 4736 (Durvalumab) for Medically Inoperable Early-Stage Non-Small Cell Lung Cancer
Secondary ID [1] 0 0
NCI-2017-00954
Secondary ID [2] 0 0
17-000004
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Carcinoma, Non-Small-Cell Lung 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Non small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Durvalumab (MEDI 4736)
Treatment: Other - Radiotherapy

Experimental: Regimen A: Phase I - The intervention will be looking at radiotherapy + drug Durvalumab (MEDI 4736)

Experimental: Regimen A: Phase II - The intervention will be looking at radiotherapy + drug Durvalumab (MEDI 4736)

Active comparator: Regimen B: Phase II - Radiotherapy alone


Treatment: Drugs: Durvalumab (MEDI 4736)
Early studies has shown to possibly reduce the growth of certain types of lung cancer

Treatment: Other: Radiotherapy
Stereotactic Body Radiation Therapy (SABR)
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase I: The number and severity of study participants' treatment-related adverse events as assessed by CTCAE v4.0.
Timepoint [1] 0 0
4 months
Primary outcome [2] 0 0
Phase II: Median Progression-Free Survival
Timepoint [2] 0 0
2 year
Secondary outcome [1] 0 0
Overall survival
Timepoint [1] 0 0
2 year
Secondary outcome [2] 0 0
Primary Tumor Control
Timepoint [2] 0 0
2 year
Secondary outcome [3] 0 0
Intralobar recurrence rates
Timepoint [3] 0 0
2 year
Secondary outcome [4] 0 0
mediastinal recurrences
Timepoint [4] 0 0
2 year
Secondary outcome [5] 0 0
hilar and mediastinal recurrences
Timepoint [5] 0 0
2 year
Secondary outcome [6] 0 0
rate of distant recurrences
Timepoint [6] 0 0
2 years
Secondary outcome [7] 0 0
rates of grade 3 or higher non-hematological toxicities
Timepoint [7] 0 0
2 years

Eligibility
Key inclusion criteria
For inclusion in the study subjects must fulfill all of the following criteria:

1. Written informed consent obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluation.
2. Newly diagnosed, untreated, biopsy proven non-small cell lung cancer.
3. Medically inoperable or patient refusal to surgery as defined by any single of the following criteria: a. Determined unfit for surgery by thoracic surgeon or radiation oncologist as documented in the medical record b. Pulmonary function test (PFTS) showing Forced Expiratory Volume in the first second (FEV1) = 1.2 L or diffusing Lung Capacity (DLC) <60%, c. Poor exercise tolerance or failed pre-operative cardiac work-up, d. Patient refusal to undergo definitive surgery as documented in clinical note by a surgeon, pulmonologist, medical oncologist, or radiation oncologist.
4. Clinically stage I disease by American Joint Committee on Cancer (AJCC) 7th edition. (N0, M0, T stages T1-T2a) or patients with stage T2bN0M0 (clinical stage IIA) disease who are medically unfit for standard of care chemotherapy as documented by a medical oncologist or radiation oncologist, or who refuse standard of care chemotherapy as documented by a medical oncologist or radiation oncologist.
5. Age > 18 years at time of study entry.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1.
7. Adequate normal organ and marrow function as defined below:

* Haemoglobin = 9.0 g/dL.
* Absolute neutrophil count (ANC) = 1.5 x 109/L (> 1500 per mm3).
* Platelet count = 100 x 109/L (>100,000 per mm3).
* 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 glutamic pyruvic 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 creatinine clearance (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)
8. Female subjects must either be of non-reproductive potential (i.e. 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.
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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. ECOG Performance status >1.
2. Patients with metastatic or node positive NSCLC.
3. Patients with prior radiation therapy to the same bronchopulmonary segment.
4. History of automimmune disease including myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematous, rheumatoid arthritis, inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis), vascular thrombosis associated with antiphospholipid syndrome, Wegner's granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, or glomerulonephritis.

a. However, patients with type 1 diabetes mellitus, vitiligo, alopecia, hypothyroidism requiring hormone replacement, Graves disease, or skin disorders not requiring systemic treatment are permitted to enroll.
5. Patients with history of idiopathic pulmonary fibrosis, idiopathic pneumonitis, drug induced pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
6. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
7. Participation in another clinical study with an investigational product during the last 6 months.
8. Any previous treatment with a Programmed Death-1 (PD1) or Programmed Death-Ligand 1(PD-L1) inhibitor, including durvalumab, and therapeutic anticancer vaccine.
9. History of another primary malignancy except for:

1. Malignancy treated with curative intent and with no known active disease =5 years before the first dose of study drug and of low potential risk for recurrence.
2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
3. Adequately treated carcinoma in situ without evidence of disease e.g., cervical cancer in situ.
10. Mean QT interval corrected for heart rate (QTc) =470 ms calculated from 3 electrocardiograms (ECGs) using Frediricia's Correction.
11. 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.
12. Any unresolved = Grade 2 pulmonary toxicity from previous anti-cancer therapy.
13. Any prior Grade =3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1.
14. History of primary immunodeficiency.
15. History of allogeneic organ transplant.
16. History of hypersensitivity to durvalumab or any excipient.
17. 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.
18. Known history of previous clinical diagnosis of tuberculosis.
19. History of leptomeningeal carcinomatosis.
20. Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab.
21. Female subjects who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control.
22. Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results.
23. Subjects with uncontrolled seizures. -

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
11/10/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/06/2026
Actual
Sample size
Target
Accrual to date
Final
18
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre - Melbourne E.
Recruitment postcode(s) [1] 0 0
3000 - Melbourne E.
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
New York

Funding & Sponsors
Primary sponsor type
Other
Name
Jonsson Comprehensive Cancer Center
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
AstraZeneca
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Ann Raldow, MD
Address 0 0
Associate Professor
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT03148327