Clinical trial NCT04745689: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Small-Cell Lung Cancer
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
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2021-02-09
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Primary outcomes:
measure: Maintenance Participants Alive and Progression Free (APF12) Per RECIST 1.1 [Efficacy]
timeFrame: Up to 12 months
Secondary outcomes:
measure: Maintenance Participants Alive at 12 Months (OS12), 15 Months (OS15), and 18 Months (OS18)
timeFrame: Up to 18 months
measure: Maintenance Participants Alive and Progression Free at 6 Months (APF6) and 9 Months (APF9) Using Investigator Assessments According to RECIST 1.1
timeFrame: Up to 9 months
measure: Objective Response Rate (ORR) for All Participants Using Investigator Assessments According to RECIST 1.1
timeFrame: Up to approximately 10 months
measure: Maintenance Participants Progression-free Survival (PFS) Using Investigator Assessments According to RECIST 1.1
timeFrame: Up to approximately 10 months
measure: Overall Survival (OS) in Maintenance Participants
timeFrame: Up to approximately 13 months
measure: AZD2811 PK: Pharmacokinetics of AZD2811 and Its Metabolites by Measuring Whole Blood Concentration
timeFrame: Up to Cycle 8 Day 8 (approximately 5 months)
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.
timeFrame: Up to Cycle 10 Day 1, approximately 7 months
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.
timeFrame: Up to Cycle 10 Day 1, approximately 7 months
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. Use of Pain Medication (Yes/No)
timeFrame: Up to Cycle 10 Day 1, approximately 7 months
Other outcomes:
Locations:
city: Grand Rapids
country: United States
facility: Research Site
state: Michigan
city: Cheongju-si
country: Korea, Republic of
facility: Research Site
city: Jinju-si
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Bydgoszcz
country: Poland
facility: Research Site
city: Olsztyn
country: Poland
facility: Research Site
city: Poznan
country: Poland
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
Study officials:
References: