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

• Sponsor: AstraZeneca (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04249362
• Collaborator: (none)
• Enrollment: 150
• Locations: 53
• Arms: 2
• Anticipated Duration (Months): 36.1
• Patients Per Site: 2.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief 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])

Condition or Disease	Intervention/Treatment	Phase
Non-small Cell Lung Cancer	Drug: Durvalumab	Phase 2

Detailed 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)

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 150 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Nov 26, 2020
• Anticipated Primary Completion Date: Nov 21, 2022
• Anticipated Study Completion Date: Nov 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort A Patients received standard radiotherapy [60 gray (Gy) ± 10% or hypofractionated BED] prior to study entry.	Drug: Durvalumab; All patients will receive 1500 mg durvalumab via IV infusion q4w for up to a maximum of 12 months.; Other Names: MEDI4736
Experimental: Cohort B Patients received palliative radiotherapy [40 to < 54 Gy or hypofractionated BED] prior to study entry.	Drug: Durvalumab; All patients will receive 1500 mg durvalumab via IV infusion q4w for up to a maximum of 12 months.; Other Names: MEDI4736

Outcome Measures

Primary Outcome Measures

1. Number of participants with Grade 3 and Grade 4 possibly-related adverse events (PRAEs) [From screening (day -28) to 6 months from the initiation of durvalumab treatment]

   To assess the safety and tolerability profile of durvalumab as defined by Grade 3 and Grade 4 PRAEs

Secondary Outcome Measures

1. Median Progression-free survival (PFS) [From the first date of treatment until the date of objective disease progression or death (up to maximum 12 months)]

   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

2. PFS at 6 months (PFS6) [From the first date of treatment until the date of objective disease progression or death (up to maximum 6 months)]

   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

3. PFS at 12 months (PFS12) [From the first date of treatment until the date of objective disease progression or death (up to maximum 12 months)]

   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

4. Median overall survival (OS) [From the first date of treatment until death due to any cause (up to maximum 12 months)]

   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

5. OS at 12 months (OS12) [From the first date of treatment until death due to any cause (up to maximum 12 months)]

   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

6. Objective response rate (ORR) [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)]

   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

7. Duration of response (DoR) [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)]

   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

8. Number of participants with lung cancer mortality [From date of treatment start until death due to lung cancer (up to maximum of 12 months)]

   To assess the efficacy of durvalumab treatment in terms of lung cancer mortality

9. Number of participants with adverse events, serious adverse events, adverse event of special interests, and immune-mediated adverse event [From screening (Day -28) till final visit (up to a maximum of 12 months)]

   To assess the safety and tolerability profile of durvalumab treatment

10. Number of participants with abnormal physical examinations [At screening]

    To assess the safety and tolerability profile of durvalumab treatment

11. Number of participants with abnormal blood pressure [From screening (Day -28) till final visit (up to a maximum of 12 months]

    To assess the safety and tolerability profile of durvalumab treatment

12. Number of participants with abnormal pulse [From screening (Day -28) till final visit (up to a maximum of 12 months)]

    To assess the safety and tolerability profile of durvalumab treatment

13. Number of participants with abnormal electrocardiograms [From screening (Day -28) till final visit (up to a maximum of 12 months)]

    To assess the safety and tolerability profile of durvalumab treatment

14. Number of participants with abnormal clinical chemistry [From screening (Day -28) till final visit (up to a maximum of 12 months)]

    To assess the safety and tolerability profile of durvalumab treatment

15. Number of participants with abnormal hematology [From screening (Day -28) till final visit (up to a maximum of 12 months]

    To assess the safety and tolerability profile of durvalumab treatment

16. Number of participants with abnormal urinalysis [From screening (Day -28) till final visit (up to a maximum of 12 months]

    To assess the safety and tolerability profile of durvalumab treatment

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 130 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

1. Life expectancy of greater than 12 weeks.

2. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Tucson	Arizona	United States	85704
2	Research Site	Tampa	Florida	United States	33612
3	Research Site	Royal Oak	Michigan	United States	48073
4	Research Site	Tacoma	Washington	United States	98405
5	Research Site	Bayonne		France	64100
6	Research Site	Limoges		France	87000
7	Research Site	Lyon Cedex 08		France	69373
8	Research Site	Marseille		France	13009
9	Research Site	Montpellier		France	34070
10	Research Site	Nimes		France	30029
11	Research Site	Rouen		France	76031
12	Research Site	Vantoux		France	57070
13	Research Site	Ancona		Italy	60126
14	Research Site	Brescia		Italy	25100
15	Research Site	Firenze		Italy	50134
16	Research Site	Genova		Italy	16132
17	Research Site	Meldola		Italy	47014
18	Research Site	Messina		Italy	98158
19	Research Site	Modena		Italy	41124
20	Research Site	Monza		Italy	20900
21	Research Site	Negrar		Italy	37024
22	Research Site	Pavia		Italy	27100
23	Research Site	Pisa		Italy	56124
24	Research Site	Ravenna		Italy	48121
25	Research Site	Roma		Italy	00128
26	Research Site	Białystok		Poland	15-044
27	Research Site	Gdańsk		Poland	80-214
28	Research Site	Koszalin		Poland	75-581
29	Research Site	Olsztyn		Poland	10-228
30	Research Site	Skorzewo		Poland	60-185
31	Research Site	Szczecin		Poland	71-730
32	Research Site	Warszawa		Poland	02-781
33	Research Site	Wroclaw		Poland	53-413
34	Research Site	Barnaul		Russian Federation	656049
35	Research Site	Kazan		Russian Federation	420029
36	Research Site	Nizhny Novgorod		Russian Federation	603081
37	Research Site	Orenburg		Russian Federation	460021
38	Research Site	St. Petersburg		Russian Federation	197002
39	Research Site	St. Petersburg		Russian Federation	197758
40	Research Site	St.Petersburg		Russian Federation	191014
41	Research Site	Ufa		Russian Federation	450054
42	Research Site	Yaroslavl		Russian Federation	150054
43	Research Site	A Coruña		Spain	15006
44	Research Site	Barcelona		Spain	8035
45	Research Site	Castello de la Plana		Spain	12002
46	Research Site	Madrid		Spain	28007
47	Research Site	Madrid		Spain	28040
48	Research Site	Madrid		Spain	28050
49	Research Site	Oviedo		Spain	33011
50	Research Site	Pamplona		Spain	31008
51	Research Site	Sabadell(Barcelona)		Spain	08208
52	Research Site	Sevilla		Spain	41013
53	Research Site	Valencia		Spain	46015

Sponsors and Collaborators

• AstraZeneca

Investigators

• Principal Investigator: Dr Andrea Riccardo Filippi, Fondazione IRCCS Policlinico San Matteo

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT04249362
• Other Study ID Numbers: D4194C00009
• First Posted: Jan 30, 2020
• Last Update Posted: Aug 23, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by AstraZeneca: Radiation therapy; Phase II; Palliative Radiotherapy
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Durvalumab

Study Results

No Results Posted as of Aug 23, 2022