Ignite Creation Date:
2025-12-24 @ 3:38 PM
Ignite Modification Date:
2025-12-25 @ 5:14 PM
Study NCT ID:
NCT07015892
Status:
NOT_YET_RECRUITING
Last Update Posted:
2025-06-11
First Post:
2025-05-28
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Dose-Escalation Radiotherapy in Limited-Stage Small Cell Lung Cancer: A Phase III Randomized Trial
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D055752', 'term': 'Small Cell Lung Carcinoma'}], 'ancestors': [{'id': 'D002283', 'term': 'Carcinoma, Bronchogenic'}, {'id': 'D001984', 'term': 'Bronchial Neoplasms'}, {'id': 'D008175', 'term': 'Lung Neoplasms'}, {'id': 'D012142', 'term': 'Respiratory Tract Neoplasms'}, {'id': 'D013899', 'term': 'Thoracic Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D008171', 'term': 'Lung Diseases'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': '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.'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 300}}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2025-09-01', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-06', 'completionDateStruct': {'date': '2028-12-31', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-06-06', 'studyFirstSubmitDate': '2025-05-28', 'studyFirstSubmitQcDate': '2025-06-06', 'lastUpdatePostDateStruct': {'date': '2025-06-11', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2025-06-11', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2028-09-01', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Progression-Free Survival (PFS)', 'timeFrame': 'From date of randomization until disease progression or death, whichever occurs first, assessed up to 5 years', 'description': '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.'}], 'secondaryOutcomes': [{'measure': 'Overall Survival (OS)', 'timeFrame': 'From date of randomization until death from any cause, assessed up to 5 years', 'description': 'Overall Survival (OS) is defined as the time from randomization to death from any cause. Patients will be followed longitudinally through scheduled clinical visits and survival status checks'}, {'measure': 'Incidence of Acute and Late Toxicities (per CTCAE v4.0)', 'timeFrame': 'From treatment initiation through 5-year follow-up', 'description': 'Toxicity will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Both acute and late toxicities (e.g., esophagitis, pneumonitis, hematologic toxicity) will be recorded during treatment and follow-up.'}, {'measure': 'Quality of Life Assessment (EORTC QLQ-C30)', 'timeFrame': 'Baseline, 3 months, 6 months, 12 months, and annually up to 5 years', 'description': 'Quality of life will be measured using the EORTC QLQ-C30. Changes in scores over time will be analyzed to evaluate treatment impact on physical, emotional, and functional well-being. The EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30) is a validated instrument designed to assess the quality of life of cancer patients. It includes 30 items organized into multi-item scales and single-item measures, covering a range of functional domains, symptoms, and overall health status. All items are scored on a 1 to 4 Likert scale (1 = "Not at all" to 4 = "Very much"), except for the two items of the global health status/QoL scale, which are scored from 1 to 7 (1 = "Very poor" to 7 = "Excellent").\n\nA high score on a functional scale reflects better functioning. A high score on a symptom scale reflects worse symptom severity. A high global health/QoL score indicates overall good health and quality of life as perceived by the patient.'}, {'measure': 'Quality of life Assesment (LC13)', 'timeFrame': 'Baseline, 3 months, 6 months, 12 months, and annually up to 5 years', 'description': 'Quality of life will be measured using lung cancer-specific module LC13. Changes in scores over time will be analyzed to evaluate treatment impact on physical, emotional, and functional well-being. The EORTC QLQ-LC13 is a lung cancer-specific module designed to be used in conjunction with the EORTC QLQ-C30. It focuses on lung cancer-related symptoms and treatment side effects, particularly from chemotherapy and radiotherapy. Just like with the QLQ-C30, raw scores are linearly transformed to a 0-100 scale for each item or symptom scale. Higher scores always reflect worse symptoms or more severe treatment-related side effects. A change of ≥10 points is typically considered clinically meaningful.\n\nCombined with the QLQ-C30, the LC13 enhances sensitivity to lung-specific disease burden and treatment toxicity.'}, {'measure': 'Quality of Life Assesment (LC29)', 'timeFrame': 'Baseline, 3 months, 6 months, 12 months, and annually up to 5 years', 'description': 'Quality of life will be measured using the lung cancer-specific module LC29. Changes in scores over time will be analyzed to evaluate treatment impact on physical, emotional, and functional well-being. The EORTC QLQ-LC29 is a lung cancer-specific quality of life questionnaire, that captures a broader and more contemporary range of lung cancer symptoms and treatment-related side effects, especially relevant to newer therapies like immunotherapy and targeted agents. The QLQ-LC29 is designed to be used in conjunction with the EORTC QLQ-C30. All items are scored on a 1-4 Likert scale:\n\n1. = Not at all\n2. = A little\n3. = Quite a bit\n4. = Very much Scores are linearly transformed to a 0-100 scale. For all LC29 items and scales: Higher scores indicate more severe symptoms or problems.\n\nLC29 retains some items from LC13 (e.g., cough, dyspnea, pain) but adds new domains (e.g., fear of progression, trouble concentrating). Provides a broader range of symptoms, including psychosocial concerns.'}, {'measure': 'Time to First Local or Distant Recurrence', 'timeFrame': 'From randomization until first documented recurrence, assessed up to 5 years', 'description': 'Time to recurrence will be measured based on clinical and radiological evaluations. Recurrences will be categorized as local (within the irradiated field) or distant (outside the thoracic field).'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Radiotherapy', 'Chemoradiotherapy', 'Dose-Response Relationship', 'Radiation'], 'conditions': ['Small Cell Lung Carcinoma']}, 'descriptionModule': {'briefSummary': "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.\n\nThe 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.\n\nThis 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", 'detailedDescription': '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).\n\nPatients 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.\n\nThe 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.\n\nLS-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.\n\nThe 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.\n\nThis 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Histologically confirmed diagnosis of small cell lung cancer (SCLC)\n* Limited-stage disease (Stage I-III; any T, any N, M0), eligible for definitive radiotherapy\n* Measurable disease according to RECIST 1.1\n* Age ≥18 years\n* ECOG performance status 0-2\n* No prior thoracic radiotherapy\n* Signed informed consent\n* Adequate hematologic function: WBC ≥3.0×10⁹/L, neutrophils ≥1.5×10⁹/L, platelets ≥100×10⁹/L, hemoglobin ≥90 g/L\n* Adequate liver and renal function: total bilirubin ≤1.5×ULN, AST/ALT ≤1.5×ULN, creatinine normal or CrCl ≥60 mL/min\n* Pulmonary function: FEV1 \\>1 L or \\>30% predicted; DLCO \\>30% predicted\n\nExclusion Criteria:\n\n* Prior surgery or radiotherapy for any lung cancer (SCLC or NSCLC)\n* Presence of malignant cells in pleural or pericardial effusion\n* Serious uncontrolled systemic disorders (e.g., active infection, unstable cardiovascular disease)\n* Medical, psychological, or social conditions that could interfere with compliance\n* Active malignancy other than SCLC (except localized prostate/breast cancer or basal cell carcinoma)\n* Refusal or inability to sign informed consent'}, 'identificationModule': {'nctId': 'NCT07015892', 'acronym': 'ESCALADOR', 'briefTitle': 'Dose-Escalation Radiotherapy in Limited-Stage Small Cell Lung Cancer: A Phase III Randomized Trial', 'organization': {'class': 'OTHER', 'fullName': 'Instituto de Investigación Biomédica de Salamanca'}, 'officialTitle': '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)', 'orgStudyIdInfo': {'id': 'ESCALADOR Study'}, 'secondaryIdInfos': [{'id': 'PI 2024 11 1761', 'type': 'REGISTRY', 'domain': 'Ethics Committee for Clinical Research of the Health Area of Salamanca (CEIm Salamanca)'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Standard Radiotherapy Arm (45 Gy BID)', '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).', 'interventionNames': ['Radiation: Thoracic Radiotherapy 45 Gy BID']}, {'type': 'EXPERIMENTAL', 'label': 'Escalated Dose Radiotherapy Arm (60 Gy BID)', '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.', 'interventionNames': ['Radiation: Thoracic Radiotherapy 60 Gy BID']}, {'type': 'EXPERIMENTAL', 'label': 'Simultaneous Integrated Boost Radiotherapy Arm (45-54 Gy BID)', '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.', 'interventionNames': ['Radiation: Thoracic Radiotherapy SIB 45-54 Gy BID']}], 'interventions': [{'name': 'Thoracic Radiotherapy 45 Gy BID', 'type': 'RADIATION', 'description': '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.', 'armGroupLabels': ['Standard Radiotherapy Arm (45 Gy BID)']}, {'name': 'Thoracic Radiotherapy 60 Gy BID', 'type': 'RADIATION', 'description': '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.', 'armGroupLabels': ['Escalated Dose Radiotherapy Arm (60 Gy BID)']}, {'name': 'Thoracic Radiotherapy SIB 45-54 Gy BID', 'type': 'RADIATION', 'description': '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.', 'armGroupLabels': ['Simultaneous Integrated Boost Radiotherapy Arm (45-54 Gy BID)']}]}, 'contactsLocationsModule': {'locations': [{'zip': '37007', 'city': 'Salamanca', 'state': 'Salamanca', 'country': 'Spain', 'contacts': [{'name': 'Iñigo San Miguel Arregui, MD PhD', 'role': 'CONTACT', 'email': 'isanm@saludcastillayleon.es', 'phone': '+34 923291600'}, {'name': 'Cristina Cigarral García, MD', 'role': 'SUB_INVESTIGATOR'}, {'name': 'Edel Del Barco Morillo, MD PhD', 'role': 'SUB_INVESTIGATOR'}, {'name': 'Lorena Bellido Hernández, MD PhD', 'role': 'SUB_INVESTIGATOR'}, {'name': 'Iñigo San Miguel Arregui, MD PhD', 'role': 'PRINCIPAL_INVESTIGATOR'}, {'name': 'Juan Alejandro Cascón Hernández, MD', 'role': 'SUB_INVESTIGATOR'}, {'name': 'Irene Jiménez García, MD', 'role': 'SUB_INVESTIGATOR'}, {'name': 'Paloma Garcia-Talavera San Miguel, MD PhD', 'role': 'SUB_INVESTIGATOR'}, {'name': 'Marta Rodríguez González, MD PhD', 'role': 'SUB_INVESTIGATOR'}, {'name': 'Francisco Javier Martín Vallejo, PhD', 'role': 'SUB_INVESTIGATOR'}], 'facility': 'Complejo Asistencial Universitario de Salamanca', 'geoPoint': {'lat': 40.96882, 'lon': -5.66388}}, {'city': 'Almería', 'country': 'Spain', 'contacts': [{'name': 'Manuel Luna, PhD', 'role': 'CONTACT', 'email': 'luna.me92@gmail.com', 'phone': '+34 950 016 000'}], 'facility': 'Hospital Universitario de Torrecardenas', 'geoPoint': {'lat': 36.83814, 'lon': -2.45974}}, {'city': 'Barakaldo', 'country': 'Spain', 'contacts': [{'name': 'Jon Cacicedo, PhD', 'role': 'CONTACT', 'email': 'jon.cacicedofernandezbobadilla@osakidetza.eus', 'phone': '+34 946 00 60 00'}], 'facility': 'Hospital Universitario de Cruces', 'geoPoint': {'lat': 43.29639, 'lon': -2.98813}}, {'city': 'Girona', 'country': 'Spain', 'contacts': [{'name': 'Ester Oliva, PhD', 'role': 'CONTACT', 'email': 'eoliva@iconcologia.net', 'phone': '+34 972 22 51 58'}], 'facility': 'Instituto Catalán de Oncología', 'geoPoint': {'lat': 41.98311, 'lon': 2.82493}}, {'city': 'Las Palmas de Gran Canaria', 'country': 'Spain', 'contacts': [{'name': 'Marta Lloret, PhD', 'role': 'CONTACT', 'email': 'mllosae@hotmail.com', 'phone': '+34 928 45 00 00'}], 'facility': 'Hospital Dr. Negrin', 'geoPoint': {'lat': 28.10178, 'lon': -15.41573}}, {'city': 'Madrid', 'country': 'Spain', 'contacts': [{'name': 'Marina Santos, PhD', 'role': 'CONTACT', 'email': 'marinasantos15@hotmail.com', 'phone': '+34 915 86 80 00'}], 'facility': 'Hospital Gregorio Marañon', 'geoPoint': {'lat': 40.4165, 'lon': -3.70256}}, {'city': 'Madrid', 'country': 'Spain', 'contacts': [{'name': 'Margarita Martín, PhD', 'role': 'CONTACT', 'email': 'oncomarga@gmail.com', 'phone': '+34 913 36 80 00'}], 'facility': 'Hospital Ramon y Cajal', 'geoPoint': {'lat': 40.4165, 'lon': -3.70256}}, {'city': 'Murcia', 'country': 'Spain', 'contacts': [{'name': 'Francisco Javier López, PhD', 'role': 'CONTACT', 'email': 'flopezsoler@hotmail.com', 'phone': '+34 968 36 95 00'}], 'facility': 'Hospital Universitario Virgen de Arrixaca', 'geoPoint': {'lat': 37.98704, 'lon': -1.13004}}, {'city': 'Santander', 'country': 'Spain', 'contacts': [{'name': 'Ivan Díaz de Cerio, PhD', 'role': 'CONTACT', 'email': 'ivancerio@hotmail.com', 'phone': '+34 942 20 25 20'}], 'facility': 'Hospital Marques de Valdecilla', 'geoPoint': {'lat': 43.46589, 'lon': -3.80493}}, {'city': 'Santiago de Compostela', 'country': 'Spain', 'contacts': [{'name': 'Begoña Taboada, PhD', 'role': 'CONTACT', 'email': 'btabval@gmail.com', 'phone': '+34 981 95 00 00'}], 'facility': 'Complejo Hospitalario Universitario de Santiago', 'geoPoint': {'lat': 42.88052, 'lon': -8.54569}}, {'city': 'Seville', 'country': 'Spain', 'contacts': [{'name': 'Jose Antonio González, PhD', 'role': 'CONTACT', 'email': 'sevilla@genesiscare.es', 'phone': '+34 954 46 70 53'}], 'facility': 'Genesis Care', 'geoPoint': {'lat': 37.38283, 'lon': -5.97317}}, {'city': 'Seville', 'country': 'Spain', 'contacts': [{'name': 'Jose Luis Lopez Guerra, PhD', 'role': 'CONTACT', 'email': 'chanodetriana@yahoo.es', 'phone': '+34 955 01 20 00'}], 'facility': 'Hospital Universitario Virgen del Rocio', 'geoPoint': {'lat': 37.38283, 'lon': -5.97317}}, {'city': 'Valencia', 'country': 'Spain', 'contacts': [{'name': 'Rodolfo Chicas, PhD', 'role': 'CONTACT', 'email': 'rchicas@ufm.edu', 'phone': '+34 961 24 40 00'}], 'facility': 'Hospital La Fe', 'geoPoint': {'lat': 39.47391, 'lon': -0.37966}}], 'centralContacts': [{'name': 'Iñigo San Miguel Arregui, MD PhD', 'role': 'CONTACT', 'email': 'isanm@saludcastillayleon.es', 'phone': '+34 923291600'}, {'name': 'Cristina Cigarral García, MD', 'role': 'CONTACT', 'email': 'ccigarral@usal.es', 'phone': '+34 923291600'}], 'overallOfficials': [{'name': 'Iñigo San Miguel Arregui, MD PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Institute of Biomedical Research of Salamanca'}]}, 'ipdSharingStatementModule': {'infoTypes': ['STUDY_PROTOCOL', 'ICF'], 'timeFrame': 'Data will be available starting 12 months after publication of primary results and for a minimum of 5 years thereafter.', 'ipdSharing': 'YES', 'description': 'Individual participant data (IPD) that underlie the results reported in future publications (after de-identification) will be made available upon reasonable request. This includes data related to baseline characteristics, treatment administration, toxicity, tumor response, survival outcomes, and quality of life assessments', 'accessCriteria': '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'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Instituto de Investigación Biomédica de Salamanca', 'class': 'OTHER'}, 'collaborators': [{'name': 'Spanish Lung Cancer Group', 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR'}}}}