Is there a survival benefit of administering thoracic radiotherapy concurrently with immunnotherapy and chemotherapy for patients with extensive stage small-cell lung cancer?

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Norwegian University Of Science And Technolology

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

11 Jan 2022 → ongoing

Decision date (initial)

2023-12-04

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-505514-15-00

EudraCT number

2021-001648-91

ClinicalTrials.gov

NCT05223647

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

To investigate whether addid thoracic radiotherapy (TRT) to durvalumab plus chemotherapy improves 1-year survival.

Secondary objectives 9

1. To investigate whether adding TRT improves 2-, 3-, 4- and 5-year overall survival.
2. To investigate whether adding TRT improves overall response rates, response rates in non-irradiated lesions and PFS.
3. To investigate whether TRT improves local control.
4. To compare the frequency and severity of adverse events between the treatment arms.
5. To compare health related quality of life between treatment arms.
6. To compare the duration of severe adverse events between the treatment arms.
7. To compare the frequency and timing of brain metastases between treatment arms.
8. To assess cognitive function in the whole study cohort and compare cognitive function between those who receive PCI and those who do not.
9. To investigate associations between outcomes of study treatment and biomarkers in tissue, blood and stool (e.g. ctDNA in blood, miRNA, gut microbiome).

Conditions and MedDRA coding

Small-cell lung cancer, extensive stage

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization (e.g. Health Insurance Portability and Accountability Act in the US, European Union [EU] Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocolrelated procedures, including screening evaluations.
2. Age at least 18 years at time of study entry.
3. ECOG performance status of 0 or 1.
4. Body weight >30 kg.
5. Adequate organ and marrow function.
6. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow-up.
7. Life expectancy of at least 3 months.
8. At least 1 lesion in the thorax, not previously irradiated, that qualifies as a RECIST 1.1 target lesion (TL) at baseline and is possible to irradiate to 30 Gy in 10 fractions. Tumor assessment by computed tomography (CT) scan or magnetic resonance imaging (MRI) must be performed within 28 days prior to randomization.
9. Histologically or cytologically confirmed SCLC. Mixed histology may be acceptable as long as the SCLC component accounts for more than 90%.
10. Stage IV disease according to the TNM v8. Patients with stage III disease are eligible if the disease is too widespread to be treated as limited stage SCLC.
11. Pulmonary function: FEV1 >1 L or >30 % of predicted value and DLCO >30 % of predicted value.
12. Female patients of childbearing potential (postmenarcheal, not postmenopausal [>12 continuous months of amenorrhea with no identified cause other than menopause], and no surgical sterilization) should use highly effective contraception and take active measures to avoid pregnancy while undergoing systemic study therapy and for at least 5 months after the last dose.
13. Patients with brain metastases are eligible provided they are asymptomatic or treated and stable on steroids and/or anticonvulsants prior to the start of treatment.

Exclusion criteria 24

1. Participation in another clinical study with an investigational product during the last 30 days.
2. Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
3. Previous chemo- or radiotherapy for SCLC. Patients who have undergone surgery, but no adjuvant therapy are eligible.
4. Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.
5. Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Chief Investigator.
6. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Chief Investigator.
7. Any concurrent chemotherapy, investigational product or biologic cancer therapy.
8. Any prior checkpoint inhibitor therapy, including durvalumab.
9. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drugs.
10. Immediate need for thoracic radiotherapy or bulky disease outside the thorax, or need for such radiotherapy before completion of chemo-immunotherapy.
11. Major surgical procedure within 28 days prior to the first dose of study drugs. Note: Local surgery of isolated lesions for palliative intent is acceptable.
12. History of allogenic organ transplantation.
13. Active or prior documented autoimmune or inflammatory disorders (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]).
14. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia or QTcF value >470 ms on ECG, 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.
15. History of another primary malignancy.
16. Leptomeningeal carcinomatosis.
17. Untreated, symptomatic central nervous system (CNS) metastases. Any neurologic symptoms that developed either as a result of the brain metastases or their treatment must have resolved or be stable either, without the use of steroids, or are stable on steroids and/or anticonvulsants prior to the start of treatment.
18. History of active primary immunodeficiency.
19. 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.
20. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab.
21. 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.
22. 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 monotherapy.
23. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
24. Judgment by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1-year overall survival

Secondary endpoints 8

1. 2-year, 3-year, 4-year and 5-year overall survival
2. Overall response rates
3. Response rates in non-irradiated lesions
4. Progression free survival
5. Progression free survival in non-irradiated lesions
6. Local control rates in the thorax
7. Frequency and severity of adverse events
8. Health-related quality of life

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Norwegian University Of Science And Technolology

Sponsor organisation

Norwegian University Of Science And Technolology

Address

Hoegskoleringen 1

City

Trondheim

Postcode

7034

Country

Norway

Scientific contact point

Organisation

Norwegian University Of Science And Technolology

Contact name

Bjørn Henning Grønberg

Public contact point

Organisation

Norwegian University Of Science And Technolology

Contact name

Ragnhild Green Helgaas

Locations

5 EU/EEA countries · 22 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Unexpected events 1 · Art. 53 CTR

Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.

Results and documents

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

Documents 19 files

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

Application history

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