Clinical Trials /

Study of AZD2811 + Durvalumab in ES-SCLC

NCT04745689

Description:

A Phase II Multicenter, Open-Label, Single Arm Study to Determine the Efficacy, Safety and Tolerability of AZD2811 and Durvalumab Combination as Maintenance Therapy After Induction with Platinum-Based Chemotherapy Combined with Durvalumab, for the First-Line Treatment of Patients with Extensive Stage Small-Cell Lung Cancer

Related Conditions:
  • Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of AZD2811 + Durvalumab in ES-SCLC
  • Official Title: A Phase II Multicenter, Open-Label, Single Arm Study to Determine the Efficacy, Safety and Tolerability of AZD2811 and Durvalumab Combination as Maintenance Therapy After Induction With Platinum-Based Chemotherapy Combined With Durvalumab, for the First-Line Treatment of Patients With Extensive Stage Small-Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: D6132C00001
  • NCT ID: NCT04745689

Conditions

  • Small-Cell Lung Cancer

Interventions

DrugSynonymsArms
DurvalumabImfinziAZD2811 + Durvalumab
AZD2811AZD2811 + Durvalumab
CarboplatinAZD2811 + Durvalumab
CisplatinAZD2811 + Durvalumab
EtoposideAZD2811 + Durvalumab

Purpose

A Phase II Multicenter, Open-Label, Single Arm Study to Determine the Efficacy, Safety and Tolerability of AZD2811 and Durvalumab Combination as Maintenance Therapy After Induction with Platinum-Based Chemotherapy Combined with Durvalumab, for the First-Line Treatment of Patients with Extensive Stage Small-Cell Lung Cancer

Detailed Description

      Primary objective of this study is to evaluate the efficacy of AZD2811 and durvalumab in
      patients who have not progressed following induction therapy with platinum-based chemotherapy
      combined with durvalumab.

      This is an open-label, single arm study. Patients will be treated in an induction phase with
      platinum-based induction therapy and durvalumab. At the end of this induction period,
      participants will be assessed for disease progression, per RECIST v1.1.

      Participants who have not progressed per RECIST v1.1 at the end of the induction phase will
      roll over into the maintenance phase of the trial, where patients will commence AZD2811 and
      durvalumab combination.

      Participants will be treated with AZD2811 and durvalumab as maintenance therapy until
      confirmed progressive disease, start of non-protocol defined anticancer therapy, unacceptable
      toxicity, or withdrawal of consent.

      If study intervention is permanently discontinued, the participant will remain in the study
      to be evaluated for safety assessment, as well as for confirmed disease progression and for
      survival.

      Targeted population are adult patients (aged ≥18 years) with histologically or cytologically
      documented extensive disease (American Joint Committee on Cancer Stage (7th edition) IV SCLC
      [T any, N any,M1 a/b]), or T3-4 due to multiple lung nodules that are too extensive or have
      tumor/nodal volume that is too large to be encompassed in a tolerable radiation plan.
      Patients must have WHO/ECOG performance status of 0 or 1.

      Tumor assessments will be performed at Screening as baseline with follow-up every 6 weeks ± 1
      week for the first 36 weeks, and then every 8 weeks ±1 week until confirmed objective disease
      progression.
    

Trial Arms

NameTypeDescriptionInterventions
AZD2811 + DurvalumabExperimentalInduction: Durvalumab + Platinum Chemotherapy (Carboplatin or cisplatin & Etoposide) Maintenance: AZD2811 + Durvalumab
  • Durvalumab
  • AZD2811
  • Carboplatin
  • Cisplatin
  • Etoposide

Eligibility Criteria

        Inclusion Criteria:

          -  Documented evidence of extensive stage SCLC (ES-SCLC)

          -  Participants must be considered suitable to receive an induction platinum-based
             chemotherapy regimen, combined with durvalumab, as first-line treatment for ES-SCLC

          -  No prior exposure to immune-mediated therapy

          -  Life expectancy ≥12 weeks at Day 1.

          -  ECOG 0 or 1 at enrolment.

        Exclusion Criteria:

          -  Any history of radiotherapy to the chest prior to systemic therapy or planned
             consolidation chest radiation therapy

          -  Has a paraneoplastic syndrome (PNS) of autoimmune nature, requiring systemic treatment
             (systemic steroids or immunosuppressive agents) or has a clinical symptomatology
             suggesting worsening of PNS

          -  Active infection including tuberculosis, HIV, hepatitis B and C

          -  Active or prior documented autoimmune or inflammatory disorders

          -  Uncontrolled intercurrent illness, including but not limited to interstitial lung
             disease.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maintenance participants alive and progression free (APF12) per RECIST 1.1 [Efficacy]
Time Frame:Up to 12 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Maintenance participants alive at 12 months (OS12), 15 months (OS15), and 18 months (OS18)
Time Frame:Up to 18 months
Safety Issue:
Description:
Measure:Maintenance participants alive and progression free at 6 months (APF6) and 9 months (APF9) using investigator assessments according to RECIST 1.1
Time Frame:Up to 9 months
Safety Issue:
Description:
Measure:Objective response rate (ORR) for all participants using investigator assessments according to RECIST 1.1
Time Frame:Approximately 3 years
Safety Issue:
Description:
Measure:Maintenance participants Progression-free survival (PFS) using investigator assessments according to RECIST 1.1
Time Frame:Approximately 3 years
Safety Issue:
Description:
Measure:Overall survival (OS) in maintenance participants
Time Frame:Approximately 3 years
Safety Issue:
Description:
Measure:Assess safety and tolerability profile in terms safety assessments, adverse events per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event [CTCAE] v5.0, and dose modifications
Time Frame:Approximately 3 years
Safety Issue:
Description:Incidence of adverse events as measured by CTCAE 5.0
Measure:Cmin of durvalumab
Time Frame:Predose Maintenance Day 1 of Cycles 5 and 7 (up to approximately 3 years)
Safety Issue:
Description:
Measure:Cmax of durvalumab
Time Frame:Predose Maintenance Day 1 of Cycles 5 and 7 (up to approximately 3 years)
Safety Issue:
Description:
Measure:AZD2811 PK: Pharmacokinetics of AZD2811 and its metabolites by measuring whole blood concentration
Time Frame:Approximately 3 years
Safety Issue:
Description:
Measure:EORTC 30: Health related quality of life based on the European Organisation for Research and Treatment of Cancer (EORTC) Quality of life Questionnaire - Cancer (QLQ-C30) v3.0.
Time Frame:Approximately 3 years
Safety Issue:
Description:The EORTC QLQ-C30 consists of 30 questions that can be combined to produce 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea/vomiting), 6 individual items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties), and a global measure of health status. The EORTC QLQ-C30 will be scored according to the EORTC QLQ-C30 Scoring Manual. Quality of life issues are assessed using a four-point scale (1= not at all, 2 = a little, 3 = quite a bit, 4 = very much), apart from two questions which are measured between 1 (Very Poor) to 7 (Excellent).
Measure:EORTC 13: Lung cancer specific quality of life based on the European Organisation for Research and Treatment of Cancer (EORTC) Quality of life Questionnaire - Lung Cancer (QLQ-LC13) v1.0.
Time Frame:Approximately 3 years
Safety Issue:
Description:The EORTC QLQ-LC13 is a 13-item questionnaire comprised of 1 symptom scale assessing dysponea, and a series of single questions assessing cough, haemoptysis, sore mouth, dysphagis, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts, and use of pain medication. All items are assessed using a Likert four-point scale (1= not at all to 4 = very much). Scoring will be done according to the EORTC QLQ-C30 Scoring Manual (Fayers et al., 2001). A high score for a symptom scale or single item represents a high level of symptomology or problems.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

  • Extensive Stage Small-Cell Lung Cancer
  • Carcinoma, Small Cell Lung
  • Oat Cell Carcinoma of Lung
  • Oat Cell Lung Cancer
  • Small Cell Cancer Of The Lung
  • Small Cell Lung Cancer
  • SCLC
  • ES-SCLC

Last Updated

March 11, 2021