Ablative STEreotactic RadiOtherapy wIth Durvalumab (MEDI4736). An open label randomized phase II trial with durvalumab following Stereotactic Body radiotherapy (SBRT) in patients with T1-2N0M0 Non-small Cell Lung Cancer (NSCLC)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Vaestra Goetalandsregionen

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

24 Jul 2024 → ongoing

Decision date (initial)

2024-07-22

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-512439-54-01

ClinicalTrials.gov

NCT03446547

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To assess whether adjuvant immunotherapy with durvalumab administered after curatively intended SBRT in T1-2N0M0 NSCLC will increase time to progression (TTP)

Conditions and MedDRA coding

Non-small cell lung cancer (NSCLC)

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Written informed consent obtained from the subject prior to performing any protocol- related procedures, including screening evaluations
2. Histological or cytological diagnosis of NSCLC
3. T1-2N0M0 tumours ≤ 5 cm
4. Peripheral tumours
5. Medically inoperable patients/at-risk patients or patients refusing surgery
6. Received no prior chemotherapy or radiation therapy for NSCLC
7. Age > 18 years at time of study entry, no upper age limit
8. WHO performance status 0-2
9. 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 ≥ 75 x 109/L (>100,000 per mm3), Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) , AST/ALT ≤ 2.5 x institutional upper limit of normal, Serum creatinine CL>30 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by chrome-EDTA or Iohexol clearance,
10. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal subjects. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy). o Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
11. 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

Exclusion criteria 18

1. Centrally located tumours
2. No regional or distant metastases are allowed (i.e. no stage IIB-IV disease)
3. Oxygen usage or a FEV1 < 0.7 L and CO diffusion capacity < 30%
4. 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
5. Participation in another clinical study with an investigational product during the last 4 weeks
6. Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
7. Second primary residual malignancy. Other malignancy diagnosed and treated > 2 years ago without relapse and deemed to have a low likelihood of relapse is allowed. (Carcinoma in situ of the cervix or adequately treated basal cell carcinoma of the skin < 2 years are allowed, as is other low-grade malignancy with low likelihood of becoming metastatic or impact on survival e.g. low-grade prostate cancer not in need of treatment)
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) 28 days prior to the first dose of study drug
9. Current or prior use of immunosuppressive medication within 14 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
10. 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: o Subjects with vitiligo or alopecia o Subjects with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement o Any chronic skin condition that does not require systemic therapy o Subjects without active disease in the last 5 years may be included but only after consultation with the study physician o Subjects with celiac disease controlled by diet alone
11. History of primary immunodeficiency
12. History of allogeneic organ transplant
13. History of hypersensitivity to durvalumab or any excipient
14. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (NYHA III-IV), uncontrolled hypertension, unstable angina pectoris, interstitial lung disease, cardiac arrhythmia, active peptic ulcer disease, active bleeding diatheses or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent
15. Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Subjects with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Subjects positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA
16. Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab
17. Female subjects who are pregnant or breastfeeding or male or female subjects of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy.
18. Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. time to progression (TTP)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Vaestra Goetalandsregionen

Sponsor organisation

Vaestra Goetalandsregionen

Address

Regionens Hus

City

Vänersborg

Postcode

462 80

Country

Sweden

Scientific contact point

Organisation

Vaestra Goetalandsregionen

Contact name

Andreas Hallqvist

Public contact point

Organisation

Vaestra Goetalandsregionen

Contact name

Andreas Hallqvist

Locations

3 EU/EEA countries · 15 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications