Dose-Escalation Radiotherapy in Limited-Stage Small Cell Lung Cancer: A Phase III Randomized Trial (ESCALADOR)

Instituto de Investigación Biomédica de Salamanca

Status and phase: Not yet enrolling; Phase 3

Conditions: Small Cell Lung Carcinoma

Treatments: Radiation: Thoracic Radiotherapy SIB 45-54 Gy BID; Radiation: Thoracic Radiotherapy 45 Gy BID; Radiation: Thoracic Radiotherapy 60 Gy BID

Study type: Interventional

Funder types: Other

Identifiers

NCT07015892

ESCALADOR Study

PI 2024 11 1761 (Registry Identifier)

Details and patient eligibility

About

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

Full 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.

Enrollment: 300 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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300 participants in 3 patient groups

Standard Radiotherapy Arm (45 Gy BID)

Active Comparator group

Description:

Patients in this group will receive concurrent chemoradiotherapy consisting of cisplatin and etoposide with standard-dose thoracic radiotherapy: 45 Gy administered in 30 fractions of 1.5 Gy twice daily (BID).

Treatment:

Radiation: Thoracic Radiotherapy 45 Gy BID

Escalated Dose Radiotherapy Arm (60 Gy BID)

Experimental group

Description:

Patients in this group will receive the same chemotherapy as Arm 1, combined with an escalated thoracic radiotherapy dose: 60 Gy delivered in 40 fractions of 1.5 Gy twice daily (BID). Dose may be reduced to 54 Gy if organs at risk exceed tolerance.

Treatment:

Radiation: Thoracic Radiotherapy 60 Gy BID

Simultaneous Integrated Boost Radiotherapy Arm (45-54 Gy BID)

Experimental group

Description:

Patients in this group will receive the same chemotherapy as in other arms, with thoracic radiotherapy delivered as a simultaneous integrated boost (SIB): 45 Gy to the general target volume and 54 Gy to the high-risk clinical target volume (CTV) in 30 fractions BID.

Treatment:

Radiation: Thoracic Radiotherapy SIB 45-54 Gy BID