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

NCT07015892 | Recruiting Phase 3

• 2 other identifiers: ESCALADOR StudyPI 2024 11 1761
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 13

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

Conditions

Small Cell Lung Carcinoma

Keywords

Radiotherapy; Chemoradiotherapy; Dose-Response Relationship; Radiation

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  Progression-Free Survival (PFS) is defined as the time from randomization to documented disease progression based on RECIST 1.1 criteria or death from any cause. Patients will be evaluated at baseline, every 3 months for the first 2 years, then every 6 months up to year 5 using imaging and clinical assessment.

  From date of randomization until disease progression or death, whichever occurs first, assessed up to 5 years

Secondary Outcomes (6)

• Overall Survival (OS)

  From date of randomization until death from any cause, assessed up to 5 years

• Incidence of Acute and Late Toxicities (per CTCAE v4.0)

  From treatment initiation through 5-year follow-up

• Quality of Life Assessment (EORTC QLQ-C30)

  Baseline, 3 months, 6 months, 12 months, and annually up to 5 years

• Quality of life Assesment (LC13)

  Baseline, 3 months, 6 months, 12 months, and annually up to 5 years

• Quality of Life Assesment (LC29)

  Baseline, 3 months, 6 months, 12 months, and annually up to 5 years

Study Arms (3)

Standard Radiotherapy Arm (45 Gy BID)

ACTIVE COMPARATOR

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).

Radiation: Thoracic Radiotherapy 45 Gy BID

Escalated Dose Radiotherapy Arm (60 Gy BID)

EXPERIMENTAL

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.

Radiation: Thoracic Radiotherapy 60 Gy BID

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

EXPERIMENTAL

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.

Radiation: Thoracic Radiotherapy SIB 45-54 Gy BID

Interventions

Thoracic Radiotherapy 60 Gy BID RADIATION

60 Gy delivered in 40 fractions of 1.5 Gy BID. A minimum dose of 54 Gy will be accepted if organ-at-risk tolerance is exceeded.

Escalated Dose Radiotherapy Arm (60 Gy BID)

Thoracic Radiotherapy 45 Gy BID RADIATION

45 Gy delivered in 30 fractions of 1.5 Gy twice daily over three weeks, with 95% of the planning target volume (PTV) receiving at least 95% of the prescribed dose.

Standard Radiotherapy Arm (45 Gy BID)

Thoracic Radiotherapy SIB 45-54 Gy BID RADIATION

45 Gy in 30 fractions (1.5 Gy BID) to PTV and 54 Gy in 30 fractions (1.8 Gy BID) to high-risk CTV. Both delivered simultaneously using 3D conformal planning.

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Spanish Lung Cancer Group: collaborator
• Instituto de Investigación Biomédica de Salamanca: lead

Study Sites (13)

Complejo Asistencial Universitario de Salamanca

Salamanca, Salamanca, 37007, Spain

RECRUITING

Hospital Universitario de Torrecardenas

Almería, Spain

NOT YET RECRUITING

Hospital Universitario de Cruces

Barakaldo, Spain

NOT YET RECRUITING

Instituto Catalán de Oncología

Girona, Spain

NOT YET RECRUITING

Hospital Dr. Negrin

Las Palmas de Gran Canaria, Spain

NOT YET RECRUITING

Hospital Gregorio Marañon

Madrid, Spain

NOT YET RECRUITING

Hospital Ramon y Cajal

Madrid, Spain

RECRUITING

Hospital Universitario Virgen de Arrixaca

Murcia, Spain

NOT YET RECRUITING

Hospital Marques de Valdecilla

Santander, Spain

NOT YET RECRUITING

Complejo Hospitalario Universitario de Santiago

Santiago de Compostela, Spain

NOT YET RECRUITING

Genesis Care

Seville, Spain

NOT YET RECRUITING

Hospital Universitario Virgen del Rocio

Seville, Spain

RECRUITING

Hospital La Fe

Valencia, Spain

NOT YET RECRUITING

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Iñigo San Miguel Arregui, MD PhD

  Institute of Biomedical Research of Salamanca

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Iñigo San Miguel Arregui, MD PhD

CONTACT

+34 923291600; isanm@saludcastillayleon.es

Cristina Cigarral García, MD

CONTACT

+34 923291600; ccigarral@usal.es

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: May 28, 2025
• First Posted: June 11, 2025
• Study Start: March 1, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: March 31, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Data will be available starting 12 months after publication of primary results and for a minimum of 5 years thereafter.
• Access Criteria: Qualified researchers with a methodologically sound proposal, as determined by the study steering committee, will be able to access the data. Requests should be directed to the study PI. A data access agreement will be required

Locations

ES (13)