Clinical trial NCT07015892: Dose-Escalation Radiotherapy in Limited-Stage Small Cell Lung Cancer: A Phase III Randomized Trial
Official title: Phase III Randomized Clinical Trial to Evaluate the Efficacy and Safety of Twice-Daily Hyperfractionated Dose-Escalated Thoracic Radiotherapy in Patients With Limited-Stage Small Cell Lung Cancer (ESCALADOR Study)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Small Cell Lung Carcinoma
Keywords: Radiotherapy
Chemoradiotherapy
Dose-Response Relationship
Radiation
Lead sponsor: Instituto de Investigación Biomédica de Salamanca
Sponsor class: OTHER
Collaborators: name: Spanish Lung Cancer Group
First posted: 2025-06-11
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Eligible patients are randomized in a 1:1:1 ratio to one of three parallel treatment arms. All arms include concurrent chemoradiotherapy with cisplatin and etoposide, but differ in the radiotherapy dose and technique: standard-dose BID radiotherapy (45 Gy), dose-escalated BID radiotherapy (60 Gy), or BID radiotherapy with a simultaneous integrated boost to 54 Gy.
Primary purpose: TREATMENT

Brief summary: This is a phase III clinical trial that aims to evaluate whether increasing the dose of radiotherapy given twice a day can improve treatment outcomes in patients with localized small cell lung cancer (SCLC). All patients will receive standard chemotherapy with cisplatin and etoposide and will be randomly assigned to one of three radiotherapy regimens.

The main objective is to determine whether this intensified radiotherapy improves progression-free survival and overall survival. The study will also compare two different dose escalation strategies and assess treatment side effects and patients' quality of life.

This research may help identify a more effective treatment approach for patients with limited-stage SCLC and could contribute to improving long-term survival in this aggressive type of cancer

Detailed description: This is a phase III, prospective, randomized, multicenter trial designed to evaluate whether a dose escalation strategy using twice-daily hyperfractionated thoracic radiotherapy can improve outcomes in patients with limited-stage small cell lung cancer (LS-SCLC).

Patients will be randomly assigned to one of three treatment arms: (A) standard-dose radiotherapy (45 Gy in 30 fractions BID), (B) escalated-dose radiotherapy (60 Gy in 40 fractions BID), or (C) standard-dose with a simultaneous integrated boost (45-54 Gy BID). All patients will receive concurrent chemotherapy with cisplatin and etoposide.

The study aims to determine if intensified radiotherapy increases progression-free survival (PFS) and overall survival (OS). Secondary objectives include comparing toxicity profiles, quality of life (using EORTC QLQ-C30 and LC13/LC29), and exploratory analyses of circulating biomarkers.

LS-SCLC has high recurrence rates despite aggressive treatment. Although BID thoracic radiotherapy (TRT) of 45 Gy is considered standard, new evidence suggests that higher doses may further improve survival without increasing toxicity. Modern radiotherapy techniques and improved imaging (e.g., PET-CT) allow more accurate targeting and potential dose escalation.

The study plans to enroll 300 patients over 36 months across 10-15 Spanish centers, coordinated by the Instituto de Investigación Biomédica de Salamanca (IBSAL) and supported by SEOR-GOECP. An interim analysis will be conducted at year 1 and year 3, with a final analysis at 5 years. Data will be collected via REDCap and follow FAIR principles. The protocol has been approved by the Salamanca Research Ethics Committee.

This trial seeks to define whether a higher radiotherapy dose improves long-term outcomes in LS-SCLC and to explore how biomarker data might inform future personalized treatments.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed diagnosis of small cell lung cancer (SCLC)
* Limited-stage disease (Stage I-III; any T, any N, M0), eligible for definitive radiotherapy
* Measurable disease according to RECIST 1.1
* Age ≥18 years
* ECOG performance status 0-2
* No prior thoracic radiotherapy
* Signed informed consent
* Adequate hematologic function: WBC ≥3.0×10⁹/L, neutrophils ≥1.5×10⁹/L, platelets ≥100×10⁹/L, hemoglobin ≥90 g/L
* Adequate liver and renal function: total bilirubin ≤1.5×ULN, AST/ALT ≤1.5×ULN, creatinine normal or CrCl ≥60 mL/min
* Pulmonary function: FEV1 \>1 L or \>30% predicted; DLCO \>30% predicted

Exclusion Criteria:

* Prior surgery or radiotherapy for any lung cancer (SCLC or NSCLC)
* Presence of malignant cells in pleural or pericardial effusion
* Serious uncontrolled systemic disorders (e.g., active infection, unstable cardiovascular disease)
* Medical, psychological, or social conditions that could interfere with compliance
* Active malignancy other than SCLC (except localized prostate/breast cancer or basal cell carcinoma)
* Refusal or inability to sign informed consent

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: From date of randomization until disease progression or death, whichever occurs first, assessed up to 5 years
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From date of randomization until death from any cause, assessed up to 5 years
measure: Incidence of Acute and Late Toxicities (per CTCAE v4.0)
timeFrame: From treatment initiation through 5-year follow-up
measure: Quality of Life Assessment (EORTC QLQ-C30)
timeFrame: Baseline, 3 months, 6 months, 12 months, and annually up to 5 years
measure: Quality of life Assesment (LC13)
timeFrame: Baseline, 3 months, 6 months, 12 months, and annually up to 5 years
measure: Quality of Life Assesment (LC29)
timeFrame: Baseline, 3 months, 6 months, 12 months, and annually up to 5 years
measure: Time to First Local or Distant Recurrence
timeFrame: From randomization until first documented recurrence, assessed up to 5 years
Other outcomes:
Locations:
city: Almería
country: Spain
facility: Hospital Universitario de Torrecardenas
city: Barakaldo
country: Spain
facility: Hospital Universitario de Cruces
city: Girona
country: Spain
facility: Instituto Catalán de Oncología
city: Las Palmas de Gran Canaria
country: Spain
facility: Hospital Dr. Negrin
city: Madrid
country: Spain
facility: Hospital Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal
city: Murcia
country: Spain
facility: Hospital Universitario Virgen de Arrixaca
city: Salamanca
country: Spain
facility: Complejo Asistencial Universitario de Salamanca
city: Santander
country: Spain
facility: Hospital Marques de Valdecilla
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago
city: Sevilla
country: Spain
facility: Genesis Care
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital La Fe
Study officials:
affiliation: Institute of Biomedical Research of Salamanca
name: Iñigo San Miguel Arregui, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: