A study on the efficacy and safety of cisplatin/etoposide and concomitant radiotherapy in combination with durvalumab, an immunotherapy, in patients with local limited small cell lung cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

16 Dec 2020 → ongoing

Decision date (initial)

2024-09-03

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca GmbH, Germany

External identifiers

EU CT number

2024-513433-20-00

EudraCT number

2020-001050-22

ClinicalTrials.gov

NCT04602533

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

Assess the efficacy in the Durvalumab treatment group versus control group measured by progression-free survival (PFS) after 18 months

Secondary objectives 1

1. Superior efficacy in the Durvalumab treatment group versus control group by means of overall survival (OS), Quality of life (QoL), overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS) at any tumor assessments, Safety and Tolerability

Conditions and MedDRA coding

Limited Disease Small Cell Lung Cancer

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Signed and dated informed consent of the subject must be available before start of any specific trial procedures
2. Male or female ≥ 18 years
3. Histological confirmed limited disease small cell lung cancer (stage 2 and 3; T2-4, N1-3, M0 according UICC8 criteria), if primarius is not eligible as RECIST1.1 target lesion (in cases with T1a and T1b) at least one lymph node must meet RECIST1.1 criteria for target lesion (≥15 mm short axis)
4. Availability of tumor tissue or fresh tumor material for translational research by central lab testing
5. ECOG PS 0-1
6. At least one measurable lesion according RECIST 1.1
7. Body weight > 30 kg
8. Adequate normal organ function: a. Hemoglobin ≥ 9.0 g/dL; b. Absolute neutrophil count (ANC) ≥ 1.5 x109/L; c. Platelet count ≥ 100 x109/L; d. AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal; e. Serum Bilirubin ≤ 1.5 x institutional upper limit of normal; f. Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min for Carboplatin, ≥60 mL/min for Cisplatin, calculated by the Cockcroft-Gault formula
9. Life expectancy of at least 12 weeks in the discretion of the investigator
10. Ability of subject to understand nature, importance and individual consequences of clinical trial

Exclusion criteria 15

1. Extensive disease small cell lung cancer (Tx, Nx, M1; stage IV)
2. Major surgical process within 28 day prior first dose of IMP and/or Radiochemotherapy
3. History of allogenic organ transplantation
4. Active or prior documented autoimmune or inflammatory disorder (including inflammatory bowel disease [e.g. 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, uveitis, etc.). The following are exceptions to this criterion: a. Patients with vitiligo or alopecia; b. Patients with hypothyroidism (e.g. following Hashimoto syndrome) stable on hormone replacement; c. Patients with any chronic skin condition that not required systemic therapy; d. Patients without active disease in the last 5 years may be included but only after consultation with the study physician; e. Patients with celiac disease controlled by diet alone
5. Uncontrolled intercurrent illness (i.e. active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, interstitial lung disease, serious chronic gastrointestinal conditions (i.e. diarrhea), psychiatric illness)
6. History of another primary malignancy in the last 5 years, except adequately treated non-melanoma skin cancer, adequately treated carcinoma in situ (without evidence of disease)
7. History of leptomeningeal carcinomatosis, or brain metastases
8. Known HIV positive and/or active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C. 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 (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA
9. Current or prior use of immunosuppressive medication within 14 days before the first dose. The following are exceptions to this criterion: a. Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection); b. Systemic corticosteroids at physiologic doses not exceeding 10 mg/day of prednisone or its equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
10. Receipt of live attenuated vaccine within 30 days prior to the first dose of IMP
11. Participation in another clinical trial with an investigational product within the last 30 days (unless during follow-up period of an interventional study)
12. Known hypersensitivity to one of the ingredients
13. Medical or psychological conditions that would jeopardize an adequate and orderly completion of the trial
14. Pregnancy, lactation and contraception: a. Women who are pregnant, nursing or who plan to become pregnant while in the trial; b. Women of child-bearing potential (WOCBP) and men who are able to father a child, unwilling to be abstinent or use highly effective methods of birth control that result in a low failure rate of less than 1% per year when used consistently and correctly beginning at informed consent, for the duration of drug treatment and for the drug out washout period (90 days after last dose of Durvalumab and/or 6 months after last dose of cisplatin and etoposide))
15. Patients who are legally institutionalized

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression-free survival (PFS) after 18 months according to RECIST1.1 as well as iRECIST for Durvalumab group only

Secondary endpoints 6

1. Progression-free survival (PSF) after other assessments
2. Overall survival (OS)
3. Overall response rate (ORR)
4. Disease control rate (DCR)
5. Safety and Tolerability
6. Symptom control assessed by patient-reported quality of life (QoL) with QLQ-C30, QLQ-LC13 and EQ-5D

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR

Sponsor organisation

Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR

Address

Langenbeckstrasse 1, Oberstadt Oberstadt

City

Mainz

Postcode

55131

Country

Germany

Scientific contact point

Organisation

Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR

Contact name

Sponsor contact point clinical trials

Public contact point

Organisation

Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR

Contact name

Sponsor contact point clinical trials

Third parties 1

Locations

1 EU/EEA country · 16 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 21 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications