Durvalumab Plus Chemotherapy in ES-SCLC (Oriental)

Sponsor

AstraZeneca (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04449861

Collaborator

(none)

166

Enrollment

Locations

Arm

24.7

Anticipated Duration (Months)

5.5

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This will be an open-label, single-arm, multicenter, Phase IIIb study to determine the safety of durvalumab + etoposide and cisplatin or carboplatin as first-line treatment in patients with extensive stage small-cell lung cancer.

Condition or Disease	Intervention/Treatment	Phase
Small Cell Lung Carcinoma Extensive Disease	Drug: Durvalumab plus chemotherapy	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

166 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Open Label, Multicenter Study of First-Line Durvalumab Plus Platinum-Based Chemotherapy in Chinese Patients With Extensive Stage Small-Cell Lung Cancer (Oriental)

Actual Study Start Date :

Dec 7, 2020

Anticipated Primary Completion Date :

Dec 30, 2022

Anticipated Study Completion Date :

Dec 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Durvalumab plus 4-6 cycles chemotherapy Participants will receive treatment with durvalumab + etoposide and either cisplatin or carboplatin (EP) for 4 to 6 cycles. Durvalumab will be administered at a dose of 1500 mg every 3 weeks (Q3W) with first-line chemotherapy (EP) and will continue to be administered as monotherapy every 4 weeks (Q4W) post-chemotherapy until progressive disease (PD). Prophylactic cranial irradiation (PCI) is allowed at the investigators' discretion as per SoC guidance for ES-SCLC. Patients will attend a safety follow up visit 90 days after last dose of durvalumab.	Drug: Durvalumab plus chemotherapy Drug: Durvalumab IV infusions every 3 weeks for 4-6 cycles and every 4 weeks thereafter until PD or other discontinuation criteria. Drug: Carboplatin 4-6 cycles every 3 weeks Drug: Cisplatin 4-6 cycles every 3 weeks Drug: Etoposide 4-6 cycles every 3 weeks

Arm

Intervention/Treatment

Experimental: Durvalumab plus 4-6 cycles chemotherapy

Participants will receive treatment with durvalumab + etoposide and either cisplatin or carboplatin (EP) for 4 to 6 cycles. Durvalumab will be administered at a dose of 1500 mg every 3 weeks (Q3W) with first-line chemotherapy (EP) and will continue to be administered as monotherapy every 4 weeks (Q4W) post-chemotherapy until progressive disease (PD). Prophylactic cranial irradiation (PCI) is allowed at the investigators' discretion as per SoC guidance for ES-SCLC. Patients will attend a safety follow up visit 90 days after last dose of durvalumab.

Drug: Durvalumab plus chemotherapy

Drug: Durvalumab IV infusions every 3 weeks for 4-6 cycles and every 4 weeks thereafter until PD or other discontinuation criteria. Drug: Carboplatin 4-6 cycles every 3 weeks Drug: Cisplatin 4-6 cycles every 3 weeks Drug: Etoposide 4-6 cycles every 3 weeks

Outcome Measures

Primary Outcome Measures

Incidence of Grade ≥3 AE and Incidence of imAE [Up to 2 years]

Secondary Outcome Measures

Pogression-free survival (PFS) using investigator assessments according to RECIST 1.1 [Up to 2 years]
Kaplan-Meier estimate of PFS curve, including quartiles (when estimable) and PFS at landmark time-points. All estimates will be accompanied by the appropriate confidence interval.
Proportion of patients alive and progression free at 12 months after first dose of study treatment (APF12) [Up to 12 months]
Kaplan-Meier estimate of the PFS curve at 12 months, together with confidence interval.
Objective response rate (ORR) using investigator assessments according to RECIST 1.1 [Up to 2 years]
The proportion of subjects with an objective response, including confidence interval.
Duration of Response (DoR) [Up to 2 years]
For responders only, the Kaplan Meier curve of DoR including quartiles and DoR at landmark times. All estimates will be accompanied by the appropriate confidence interval.
Overall survival (OS) [Up to 2 years]
Kaplan-Meier estimate of OS curve, including quartiles (when estimable) and OS at landmark time-points. All estimates will be accompanied by the appropriate confidence interval.
Overall survival at 12 months (OS12) after first dose of study treatment [Up to 12 months]
Kaplan-Meier estimate of the OS curve at 12 months, together with confidence interval
AE (including all AEs, SAEs, adverse event of special interest [AESI], AE resulting in treatment discontinuation) [Up to 2 years]
Estimates of the incidence of AEs overall, and by different categories of AE

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

For inclusion in the study, patients should fulfill the following criteria:

Male or female ≥18 years at the time of Screening.
Written informed consent obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
Histologically or cytologically documented extensive stage SCLC (stage IV [T any, N any, M1 a/b], or with 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, according to American Joint Committee on Cancer Stage 8th edition).

Brain metastases; must be asymptomatic or treated and stable off steroids and anti-convulsants for at least 1 month prior to study treatment. Patients with suspected brain metastases at screening should have a CT/MRI of the brain prior to study entry.

Patients must be considered suitable to receive a platinum-based chemotherapy regimen as 1st line treatment for the ES-SCLC. Chemotherapy must contain either cisplatin or carboplatin in combination with etoposide.
Life expectancy ≥12 weeks at Day 1.
World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2 at enrollment.

Note: Patients with PS2 will be limited to a maximum of 20% of the total study population; once this limit is met, additional enrolled patients must have PS 0-1.

Body weight >30 kg.
At least 1 lesion, not previously irradiated, that can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes which must have a short axis ≥15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and that is suitable for accurate repeated measurements as per RECIST 1.1 guidelines.
Baseline CT/MRI results of the chest and abdomen (including liver and adrenal glands) within 28 days prior to the treatment initiation.
No prior exposure to immune-mediated therapy including, but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD-L1, and anti-programmed cell death ligand 2 (anti-PD-L2) antibodies, excluding therapeutic anticancer vaccines.
Adequate organ and marrow function as defined below (test can be repeated once if necessary):

Hemoglobin ≥9.0 g/dL.
Absolute neutrophil count ≥1.5 × 10^9/L (use of granulocyte colony-stimulating factor is not permitted at within 7 days before testingscreening).
Platelet count ≥100 × 10^9/L.
Serum bilirubin ≤1.5 × the upper limit of normal (ULN).
In patients without hepatic metastasis: ALT and AST ≤2.5 × ULN.
In patients with hepatic metastases, ALT and AST ≤5 × ULN.
Measured or calculated creatinine clearance: >60mL/min for patients planned to be treated with cisplatin and >40mL/min for patients planned to be treated with carboplatin

Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause.

The following age-specific requirements apply:

Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).

Patients should not enter the study if any of the following exclusion criteria are fulfilled:

Previous IP assignment in the present study.
Medical contraindication to etoposide-platinum (carboplatin or cisplatin)-based chemotherapy.
Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
Received prior systemic therapy for ES-SCLC. Patients who have received prior chemoradiotherapy for limited-stage SCLC must have been treated with curative intent and experienced a treatment-free interval of at least 6 months since last chemotherapy, radiotherapy, or chemoradiotherapy cycle from diagnosis of ES-SCLC
Any condition that, in the opinion of the treating physician, would interfere with evaluation of the study drug or interpretation of patient safety.
Planned consolidation chest radiation therapy. Radiation therapy outside of the chest for palliative care (ie, bone metastasis) is allowed but must be completed before first dose of the study medication.
Major surgical procedure (as defined by the investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
History of allogeneic organ transplantation.
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 or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis with the exception of diverticulosis, systemic lupus erythematosus, sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, and uveitis, etc]). The following are exceptions to this criterion:

Patients with vitiligo or alopecia
Patients with hypothyroidism (eg, following Hashimoto syndrome) and stable on hormone replacement
Any chronic skin condition that does not require systemic therapy
Patients without active disease in the last 5 years may be included but only after consultation with the Study Physician
Patients with celiac disease controlled by diet alone

Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, active interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
History of active primary immunodeficiency.
Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice), hepatitis B (known positive HBV surface antigen [HbsAg] result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HbsAg) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:

Intranasal, inhaled, topical steroids or local steroid injections (eg, intra articular
injection).
Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent.
Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication). Premedication with steroids for chemotherapy is acceptable.

Receipt of live, attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP.
Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from Screening to 90 days after the last dose of durvalumab.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Research Site	Baoding	China	071000
2	Research Site	Changchun	China	130012
3	Research Site	Chengdu	China	610041
4	Research Site	Dalian	China	116001
5	Research Site	Dongyang	China	322100
6	Research Site	Guangdong	China	510120
7	Research Site	Guangzhou	China	510080
8	Research Site	Guangzhou	China	510280
9	Research Site	Haerbin	China	150081
10	Research Site	Hangzhou	China	310016
11	Research Site	Hangzhou	China	310022
12	Research Site	Hefei	China	230000
13	Research Site	Huai'an	China	223000
14	Research Site	Jiangyin	China	214400
15	Research Site	Jinan	China	250117
16	Research Site	Jinhua	China	321099
17	Research Site	Nanchang	China	330000
18	Research Site	Nanjing	China	210032
19	Research Site	Ningbo	China	315000
20	Research Site	Qingdao	China	266100
21	Research Site	Shanghai	China	200025
22	Research Site	Shanghai	China	200040
23	Research Site	ShenZhen	China	518020
24	Research Site	Taizhou	China	318000
25	Research Site	Tianjin	China	300060
26	Research Site	Whenzhou	China	325000
27	Research Site	Wuhan	China	430022
28	Research Site	Wuxi	China	214023
29	Research Site	Yangzhou	China	225012
30	Research Site	Zhengzhou	China	450000

Sponsors and Collaborators

AstraZeneca

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

AstraZeneca

ClinicalTrials.gov Identifier:

NCT04449861

Other Study ID Numbers:

D419BR00018

First Posted:

Jun 29, 2020

Last Update Posted:

Aug 15, 2022

Last Verified:

Aug 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Small Cell Lung Carcinoma

Durvalumab

Study Results

No Results Posted as of Aug 15, 2022