TAZMAN: Study of AZD2811 + Durvalumab in ES-SCLC

Sponsor

AstraZeneca (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04745689

Collaborator

(none)

Enrollment

Locations

Arm

32.2

Anticipated Duration (Months)

2.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Small-Cell Lung Cancer	Drug: Durvalumab Drug: AZD2811 Drug: Carboplatin Drug: Cisplatin Drug: Etoposide	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

31 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Masking Description:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Feb 23, 2021

Anticipated Primary Completion Date :

Mar 31, 2023

Anticipated Study Completion Date :

Oct 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AZD2811 + Durvalumab Induction: Durvalumab + Platinum Chemotherapy (Carboplatin or cisplatin & Etoposide) Maintenance: AZD2811 + Durvalumab	Drug: Durvalumab IV infusions through induction phase. IV infusions through maintenance phase until PD or other discontinuation criteria. Other Names: Imfinzi Drug: AZD2811 IV infusions through maintenance phase until PD or other discontinuation criteria. Drug: Carboplatin IV infusions through induction phase if chosen by Investigator. Drug: Cisplatin IV infusions through induction phase if chosen by Investigator. Drug: Etoposide IV infusions through induction phase.

Arm

Intervention/Treatment

Experimental: AZD2811 + Durvalumab

Induction: Durvalumab + Platinum Chemotherapy (Carboplatin or cisplatin & Etoposide) Maintenance: AZD2811 + Durvalumab

Drug: Durvalumab

IV infusions through induction phase. IV infusions through maintenance phase until PD or other discontinuation criteria.

Other Names:

Imfinzi

Drug: AZD2811

IV infusions through maintenance phase until PD or other discontinuation criteria.

Drug: Carboplatin

IV infusions through induction phase if chosen by Investigator.

Drug: Cisplatin

IV infusions through induction phase if chosen by Investigator.

Drug: Etoposide

IV infusions through induction phase.

Outcome Measures

Primary Outcome Measures

Maintenance participants alive and progression free (APF12) per RECIST 1.1 [Efficacy] [Up to 12 months]

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Grand Rapids	Michigan	United States	49503
2	Research Site	Cheongju-si		Korea, Republic of	28644
3	Research Site	Jinju-si		Korea, Republic of	52727
4	Research Site	Seoul		Korea, Republic of	03722
5	Research Site	Seoul		Korea, Republic of	06591
6	Research Site	Seoul		Korea, Republic of	138-736
7	Research Site	Seoul		Korea, Republic of	6351
8	Research Site	Bydgoszcz		Poland	85-796
9	Research Site	Olsztyn		Poland	10-357
10	Research Site	Poznan		Poland	60-693
11	Research Site	Sevilla		Spain	41071
12	Research Site	Valencia		Spain	46015