Clinical Trials /

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

NCT04249362

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 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]).

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Durvalumab Following Radiation Therapy in Patients With Stage 3 Unresectable NSCLC Ineligible for Chemotherapy
  • 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 IDs

  • ORG STUDY ID: D4194C00009
  • NCT ID: NCT04249362

Conditions

  • Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
DurvalumabMEDI4736Cohort A

Purpose

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]).

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)
    

Trial Arms

NameTypeDescriptionInterventions
Cohort AExperimentalPatients received standard radiotherapy [60 gray (Gy) ± 10% or hypofractionated BED] prior to study entry.
  • Durvalumab
Cohort BExperimentalPatients received palliative radiotherapy [40 to < 54 Gy or hypofractionated BED] prior to study entry.
  • Durvalumab

Eligibility Criteria

        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.
      
Maximum Eligible Age:130 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with Grade 3 and Grade 4 possibly-related adverse events (PRAEs)
Time Frame:From screening (day -28) to 6 months from the initiation of durvalumab treatment
Safety Issue:
Description:To assess the safety and tolerability profile of durvalumab as defined by Grade 3 and Grade 4 PRAEs

Secondary Outcome Measures

Measure:Median Progression-free survival (PFS)
Time Frame:From the first date of treatment until the date of objective disease progression or death (up to maximum 12 months)
Safety Issue:
Description: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
Measure:PFS at 6 months (PFS6)
Time Frame:From the first date of treatment until the date of objective disease progression or death (up to maximum 6 months)
Safety Issue:
Description: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
Measure:PFS at 12 months (PFS12)
Time Frame:From the first date of treatment until the date of objective disease progression or death (up to maximum 12 months)
Safety Issue:
Description: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
Measure:Median overall survival (OS)
Time Frame:From the first date of treatment until death due to any cause (up to maximum 12 months)
Safety Issue:
Description: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
Measure:OS at 12 months (OS12)
Time Frame:From the first date of treatment until death due to any cause (up to maximum 12 months)
Safety Issue:
Description: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
Measure:Objective response rate (ORR)
Time Frame: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)
Safety Issue:
Description: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
Measure:Duration of response (DoR)
Time Frame: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)
Safety Issue:
Description: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
Measure:Number of participants with lung cancer mortality
Time Frame:From date of treatment start until death due to lung cancer (up to maximum of 12 months)
Safety Issue:
Description:To assess the efficacy of durvalumab treatment in terms of lung cancer mortality
Measure:Number of participants with adverse events, serious adverse events, adverse event of special interests, and immune-mediated adverse event
Time Frame:From screening (Day -28) till final visit (up to a maximum of 12 months)
Safety Issue:
Description:To assess the safety and tolerability profile of durvalumab treatment
Measure:Number of participants with abnormal physical examinations
Time Frame:At screening
Safety Issue:
Description:To assess the safety and tolerability profile of durvalumab treatment
Measure:Number of participants with abnormal blood pressure
Time Frame:From screening (Day -28) till final visit (up to a maximum of 12 months
Safety Issue:
Description:To assess the safety and tolerability profile of durvalumab treatment
Measure:Number of participants with abnormal pulse
Time Frame:From screening (Day -28) till final visit (up to a maximum of 12 months)
Safety Issue:
Description:To assess the safety and tolerability profile of durvalumab treatment
Measure:Number of participants with abnormal electrocardiograms
Time Frame:From screening (Day -28) till final visit (up to a maximum of 12 months)
Safety Issue:
Description:To assess the safety and tolerability profile of durvalumab treatment
Measure:Number of participants with abnormal clinical chemistry
Time Frame:From screening (Day -28) till final visit (up to a maximum of 12 months)
Safety Issue:
Description:To assess the safety and tolerability profile of durvalumab treatment
Measure:Number of participants with abnormal hematology
Time Frame:From screening (Day -28) till final visit (up to a maximum of 12 months
Safety Issue:
Description:To assess the safety and tolerability profile of durvalumab treatment
Measure:Number of participants with abnormal urinalysis
Time Frame:From screening (Day -28) till final visit (up to a maximum of 12 months
Safety Issue:
Description:To assess the safety and tolerability profile of durvalumab treatment

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

  • Radiation therapy
  • Phase II
  • Palliative Radiotherapy

Last Updated

June 17, 2020