Study of AZD2811 + Durvalumab in ES-SCLC

Small-Cell Lung Cancer Clinical Trial

— TAZMAN  

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 Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04745689
• Other study ID #: D6132C00001
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: February 23, 2021
• Est. completion date: March 31, 2023

Study information

• Verified date: December 2022
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 31
• Est. completion date: March 31, 2023
• Est. primary completion date: June 18, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

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.

Related Conditions & MeSH terms

• Lung Neoplasms
• Small Cell Lung Carcinoma
• Small-Cell Lung Cancer

Intervention

Drug:
• Durvalumab
IV infusions through induction phase. IV infusions through maintenance phase until PD or other discontinuation criteria.
• AZD2811
IV infusions through maintenance phase until PD or other discontinuation criteria.
• Carboplatin
IV infusions through induction phase if chosen by Investigator.
• Cisplatin
IV infusions through induction phase if chosen by Investigator.
• Etoposide
IV infusions through induction phase.

Locations

Country	Name	City	State
Korea, Republic of	Research Site	Cheongju-si
Korea, Republic of	Research Site	Jinju-si
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Poland	Research Site	Bydgoszcz
Poland	Research Site	Olsztyn
Poland	Research Site	Poznan
Spain	Research Site	Sevilla
Spain	Research Site	Valencia
United States	Research Site	Grand Rapids	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Korea, Republic of,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maintenance participants alive and progression free (APF12) per RECIST 1.1 [Efficacy]		Up to 12 months
Secondary	Maintenance participants alive at 12 months (OS12), 15 months (OS15), and 18 months (OS18)		Up to 18 months
Secondary	Maintenance participants alive and progression free at 6 months (APF6) and 9 months (APF9) using investigator assessments according to RECIST 1.1		Up to 9 months
Secondary	Objective response rate (ORR) for all participants using investigator assessments according to RECIST 1.1		Approximately 3 years
Secondary	Maintenance participants Progression-free survival (PFS) using investigator assessments according to RECIST 1.1		Approximately 3 years
Secondary	Overall survival (OS) in maintenance participants		Approximately 3 years
Secondary	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	Incidence of adverse events as measured by CTCAE 5.0	Approximately 3 years
Secondary	Cmin of durvalumab		Predose Maintenance Day 1 of Cycles 5 and 7 (up to approximately 3 years)
Secondary	Cmax of durvalumab		Predose Maintenance Day 1 of Cycles 5 and 7 (up to approximately 3 years)
Secondary	AZD2811 PK: Pharmacokinetics of AZD2811 and its metabolites by measuring whole blood concentration		Approximately 3 years
Secondary	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.	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).	Approximately 3 years
Secondary	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.	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.	Approximately 3 years