Chemo-immunotherapy Plus Thoracic Radiotherapy in Extensive Stage Small-cell Lung Cancer (TRIPLEX)

Norwegian University of Science and Technology

Status and phase: Terminated; Phase 3

Conditions: Small-cell Lung Cancer

Treatments: Procedure: Thoracic radiotherapy; Drug: Chemo-immunotherapy

Study type: Interventional

Funder types: Other

Identifiers

NCT05223647

EC#230766

2020203 (Other Grant/Funding Number)

Details and patient eligibility

About

Studies have shown that combining chemotherapy and immune checkpoint inhibitors (ICI) prolongs survival compared with chemotherapy alone in extensive stage small-cell lung cancer (ES SCLC), but the survival benefit is modest. The main aim of this trial is to investigate whether there is a synergistic/additive effect of concurrent thoracic radiotherapy in ES SCLC patients receiving carboplatin/etoposide/durvalumab.

Full description

Studies show that adding ICI therapy to standard chemotherapy prolongs survival in ES SCLC. The survival benefit, however, is modest, and there is a need for more effective therapy. It has been hypothesized that there is a synergistic effect of combining ICI with radiotherapy. In this randomized phase III study, the main aim is to investigate whether concurrent thoracic radiotherapy of 30 Gy/10 fractions improves survival in ES SCLC patients receiving carboplatin/etoposide/durvalumab.

It is currently not possible to classify the patients who benefit from ICIs in SCLC. In this study, biological material (tissue, blood, feces) which will be analyzed for potential predictive and prognostic biomarkers.

Prophylactic cranial irradiation in ES SCLC is debated, mainly due to the potentially detrimental effect on cognition. Thus, frequency and timing of brain metastases and cognitive function will be assessed before, during and after study treatment.

Enrollment: 239 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age > 18 years at time of study entry
2. ECOG performance status of 0 or 1
3. Body weight >30 kg
4. Adequate bone marrow, liver and kidney function
5. Life expectancy of at least 3 months
6. At least one measurable (RECIST 1.1), thoracic lesion that can be irradiated with 30 Gy/10 fractions
7. Histologically or cytologically confirmed SCLC
8. Stage III-IV disease (TNM v8)
9. FEV1 >1 L or >30 % of predicted value and DLCO >30 % of predicted value
10. 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

1. Previous chemo-, immuno- or radiotherapy for SCLC
2. Major surgical procedure last 28 days
3. History of allogenic organ transplantation, autoimmune disease, immunodeficiency, hepatitis or HIV
4. Uncontrolled intercurrent illness
5. Other active malignancy
6. Leptomeningeal carcinomatosis
7. Immunosuppressive medication
8. Pregnant or breastfeeding women

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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239 participants in 2 patient groups

Chemo-immunotherapy plus thoracic radiotherapy

Experimental group

Description:

Four courses of carboplatin/etoposide/durvalumab every 3 weeks followed by durvalumab every 4 weeks until intolerable toxicity, progressive disease leading to a need for other treatment, or until the patient no longer wishes to continue treatment. Thoracic radiotherapy of 30 Gy/10 fractions between 2nd and 3rd carboplatin/etoposide/durvalumab course.

Treatment:

Drug: Chemo-immunotherapy

Procedure: Thoracic radiotherapy

Chemo-immunotherapy

Active Comparator group

Description:

Four courses of carboplatin/etoposide/durvalumab every 3 weeks followed by durvalumab every 4 weeks until intolerable toxicity, progressive disease leading to a need for other treatment, or until the patient no longer wishes to continue treatment.

Treatment:

Drug: Chemo-immunotherapy