Study of Durvalumab Following Radiation Therapy in Patients With Stage 3 Unresectable NSCLC Ineligible for Chemotherapy

Non-small Cell Lung Cancer Clinical Trial

— DUART  

Official title:

A Phase II, Open-label, Multicenter, International Study of Durvalumab Following Radiation Therapy in Patients With Stage III, Unresectable Non-Small Cell Lung Cancer Who Are Ineligible for Chemotherapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04249362
• Other study ID #: D4194C00009
• Secondary ID: 2019-004336-31
• Status: Completed
• Phase: Phase 2
• Start date: November 26, 2020
• Est. completion date: December 5, 2023

Study information

• Verified date: March 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase II open-label, single-arm, multicenter, international study to evaluate the clinical activity of durvalumab in patients with Stage III unresectable NSCLC who are deemed to be ineligible for chemotherapy per Investigator assessment. Patients will be enrolled into 2 cohorts according to radiotherapy pretreatment dose (Cohort A: standard radiation therapy [60 gray (Gy) ± 10% or hypofractionated bioequivalent dose (BED)]; Cohort B: palliative radiation therapy [40 to < 54 Gy or hypofractionated BED])

Description:

This is a Phase II open-label, single-arm, multicenter, international study to evaluate the clinical activity of durvalumab in patients with Stage III unresectable NSCLC who have an Eastern Cooperative Oncology Group (ECOG) PS of 0 to 2 and who were treated with radiotherapy but are ineligible for chemotherapy. Patients will be enrolled into 2 cohorts according to the dose of radiotherapy received prior to study entry (Cohort A: Standard Radiotherapy [60 Gy ± 10% or hypofractionated BED]; Cohort B: Palliative Radiotherapy [40 to < 54 Gy or hypofractionated BED]). Patients must not have progressed following radiation therapy, and radiation therapy must be completed within 6 weeks (42 days) prior to first study drug administration. The last dose of radiation therapy is defined as the day of the last radiation treatment session. All patients will receive 1500 mg durvalumab via IV infusion every 4 weeks (q4w) for up to a maximum of 12 months (up to 13 doses/cycles)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 102
• Est. completion date: December 5, 2023
• Est. primary completion date: March 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

Inclusion Criteria:

1. Capable of giving signed informed consent.

2. Age = 18 years at study entry.

3. Histologically or cytologically documented NSCLC with locally-advanced, unresectable Stage III disease.

4. Deemed ineligible for chemotherapy per Investigator assessment.

5. Receipt of radiation therapy that was completed within 42 days prior to first study drug administration.

6. Must have received a total dose of radiation of 40 to 66 Gy (standard or hypofractionated BED).

7. Must not have progressed following radiation therapy, as per Investigator assessed RECIST 1.1 criteria: a) Patients with measurable disease and/or nonmeasurable and/or no evidence of disease assessed at baseline by computed tomography /magnetic resonance imaging will be eligible for this study. b) Prior irradiated lesions may be considered measurable and selected as target lesions (TLs) providing they fulfill the other criteria for measurability.

8. World Health Organization/ECOG performance status of =2.

9. No prior exposure to immune-mediated therapy including, but not limited to, anti-CTLA-4, anti-PD-1, anti-PD-L1, and antiprogrammed cell death ligand 2 (anti-PD-L2) antibodies, excluding therapeutic anticancer vaccines.

10. Patients must have adequate organ and marrow function as defined below:

• Hemoglobin = 9.0 g/dL
• Absolute neutrophil count = 1.0 × 109 /L
• Platelet count = 75 × 109/L
• Serum bilirubin = 1.5 × the upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome.
• Alanine aminotransferase and aspartate aminotransferase = 2.5 × ULN
• Measured creatinine clearance > 30 mL/min or calculated CL > 30 mL/min as determined by Cockcroft-Gault

11. Life expectancy of greater than 12 weeks.

12. Body weight greater than 30 kg at study entry and at first study drug administration

Exclusion Criteria:

1. Patients with locally-advanced NSCLC whose disease has progressed following radiation therapy.

2. Mixed small cell lung cancer and NSCLC histology.

3. History of allogeneic organ transplantation.

4. Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative, systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome).

5. Uncontrolled intercurrent illness (e.g., ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris)

6. History of another primary malignancy except for (a) malignancy treated with curative intent and with no known active disease = 5 years before the first study drug administration, (b) adequately treated nonmelanoma skin cancer or lentigo maligna without evidence of disease, and c) treated carcinoma in situ without evidence of disease.

7. History of leptomeningeal carcinomatosis

8. History of active primary immunodeficiency

9. Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus

10. Any unresolved toxicity NCI CTCAE Grade = 2 from previous anticancer therapy with the exception of alopecia, vitiligo, lymphopenia, and the laboratory values defined in the inclusion criteria

11. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.

12. Receipt of live attenuated vaccine within 30 days prior to the first dose of durvalumab

13. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of durvalumab.

14. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab.

15. Participation in another clinical study with an IP administered in the last 4 weeks.

16. Concurrent enrollment in another clinical study, unless it is an observational (noninterventional) clinical study or during the follow-up period of an interventional study

17. Prior randomization or treatment in a previous durvalumab clinical study regardless of treatment arm assignment

18. Patients who refuse chemotherapy by their own decision.

19. Involvement in the planning and/or conduct of the study

20. Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control.

21. Judgment by the Investigator that the patient should not participate in the study

22. Genetics research study (optional):

Exclusion criteria for participation in the optional genetics research component of the study include: a) Previous allogeneic bone marrow transplant b)Nonleukocyte-depleted whole blood transfusion within 120 days of genetic sample collection.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

Drug:
• Durvalumab
All patients will receive 1500 mg durvalumab via IV infusion q4w for up to a maximum of 12 months.

Locations

Country	Name	City	State
France	Research Site	Limoges
France	Research Site	Marseille
France	Research Site	Montpellier
France	Research Site	Nimes
France	Research Site	Rouen
Italy	Research Site	Brescia
Italy	Research Site	Firenze
Italy	Research Site	Genova
Italy	Research Site	Meldola
Italy	Research Site	Messina
Italy	Research Site	Modena
Italy	Research Site	Monza
Italy	Research Site	Negrar
Italy	Research Site	Pavia
Italy	Research Site	Pisa
Italy	Research Site	Ravenna
Italy	Research Site	Roma
Poland	Research Site	Bialystok
Poland	Research Site	Gdansk
Poland	Research Site	Olsztyn
Poland	Research Site	Szczecin
Poland	Research Site	Warszawa
Russian Federation	Research Site	St. Petersburg
Russian Federation	Research Site	St. Petersburg
Russian Federation	Research Site	Ufa
Spain	Research Site	A Coruña
Spain	Research Site	Barcelona
Spain	Research Site	Castello de la Plana
Spain	Research Site	Madrid
Spain	Research Site	Oviedo
Spain	Research Site	Pamplona
Spain	Research Site	Sabadell(Barcelona)
United States	Research Site	Royal Oak	Michigan
United States	Research Site	Tampa	Florida
United States	Research Site	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  France,  Italy,  Poland,  Russian Federation,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with Grade 3 and Grade 4 possibly-related adverse events (PRAEs)	To assess the safety and tolerability profile of durvalumab as defined by Grade 3 and Grade 4 PRAEs	From screening (day -28) to 6 months from the initiation of durvalumab treatment
Secondary	Median Progression-free survival (PFS)	To assess the efficacy of durvalumab treatment . PFS is defined as the time from the first date of treatment until the date of objective disease progression or death regardless of whether the patient withdraws from investigational product (IP) or receives another anticancer therapy prior to progression	From the first date of treatment until the date of objective disease progression or death (up to maximum 12 months)
Secondary	PFS at 6 months (PFS6)	To assess the efficacy of durvalumab treatment . PFS is defined as the time from the first date of treatment until the date of objective disease progression or death regardless of whether the patient withdraws from IP or receives another anticancer therapy prior to progression	From the first date of treatment until the date of objective disease progression or death (up to maximum 6 months)
Secondary	PFS at 12 months (PFS12)	To assess the efficacy of durvalumab treatment. PFS is defined as the time from the first date of treatment until the date of objective disease progression or death regardless of whether the patient withdraws from IP or receives another anticancer therapy prior to progression	From the first date of treatment until the date of objective disease progression or death (up to maximum 12 months)
Secondary	Median overall survival (OS)	To assess the efficacy of durvalumab treatment. OS is defined as the time from the first date of treatment until death due to any cause	From the first date of treatment until death due to any cause (up to maximum 12 months)
Secondary	OS at 12 months (OS12)	To assess the efficacy of durvalumab treatment. OS is defined as the time from the first date of treatment until death due to any cause	From the first date of treatment until death due to any cause (up to maximum 12 months)
Secondary	Objective response rate (ORR)	To assess the efficacy of durvalumab treatment in terms of ORR based on Investigator assessments per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria	From 8 weeks ±1 week after investigational product (IP) treatment initiation and continue every 8 weeks (q8w) ±1 week through 48 weeks and every 12 weeks (q12w) ±1 week until disease progression (up to maximum of 12 months)
Secondary	Duration of response (DoR)	To assess the efficacy of durvalumab treatment in terms of DoR. DoR is defined as the time from the date of first documented response per RECIST1.1 until the first date of documented progression per RECIST1.1 or death in the absence of disease progression	From 8 weeks ±1 week after IP treatment initiation and continue q8w ±1 week through 48 weeks and q12w ±1 week until disease progression (up to maximum of 12 months)
Secondary	Number of participants with lung cancer mortality	To assess the efficacy of durvalumab treatment in terms of lung cancer mortality	From date of treatment start until death due to lung cancer (up to maximum of 12 months)
Secondary	Number of participants with adverse events, serious adverse events, adverse event of special interests, and immune-mediated adverse event	To assess the safety and tolerability profile of durvalumab treatment	From screening (Day -28) till final visit (up to a maximum of 12 months)
Secondary	Number of participants with abnormal physical examinations	To assess the safety and tolerability profile of durvalumab treatment	At screening
Secondary	Number of participants with abnormal blood pressure	To assess the safety and tolerability profile of durvalumab treatment	From screening (Day -28) till final visit (up to a maximum of 12 months
Secondary	Number of participants with abnormal pulse	To assess the safety and tolerability profile of durvalumab treatment	From screening (Day -28) till final visit (up to a maximum of 12 months)
Secondary	Number of participants with abnormal electrocardiograms	To assess the safety and tolerability profile of durvalumab treatment	From screening (Day -28) till final visit (up to a maximum of 12 months)
Secondary	Number of participants with abnormal clinical chemistry	To assess the safety and tolerability profile of durvalumab treatment	From screening (Day -28) till final visit (up to a maximum of 12 months)
Secondary	Number of participants with abnormal hematology	To assess the safety and tolerability profile of durvalumab treatment	From screening (Day -28) till final visit (up to a maximum of 12 months
Secondary	Number of participants with abnormal urinalysis	To assess the safety and tolerability profile of durvalumab treatment	From screening (Day -28) till final visit (up to a maximum of 12 months