Thoracic Radiotherapy Plus Maintenance Durvalumab After First Line Carboplatin and Etoposide Plus Durvalumab in Extensive-stage Disease Small Cell Lung Cancer (ED-SCLC).

NCT04472949 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: SAKK 15/19
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 14

Brief Summary

Standard of care for Extensive-Stage Disease (ED) Small Cell Lung Cancer (SCLC) as first-line treatment is 4 to 6 cycles of platinum based chemotherapy (carboplatin or cisplatin) in combination with etoposide. However, the outcome of the disease remains poor with a median overall survival of approximately 10 months, mainly caused by rapid development of drug resistance. The risk of intrathoracic recurrences can be reduced and an improved 2-year survival can be achieved with the addition of thoracic radiotherapy (tRT). The main objective of the trial is to evaluate the efficacy of tRT combined with maintenance durvalumab in SCLC after chemoimmunotherapy. Secondary objective is to evaluate the safety of tRT combined with maintenance durvalumab in SCLC after chemo-immunotherapy. For this trial durvalumab is the IMP. Patients will start with an induction phase (part 1): Patients will receive durvalumab in combination with carboplatin and etoposide for 4 cycles of 21 days. Patients with CR; PR or SD after the induction phase, will transfer to the maintenance phase (part 2): Patients will receive durvalumab treatment up to PD or max. 2 years, i.e. 26 maintenance cycles, in combination with tRT. Patients with PD after the induction phase will transfer to the follow-up phase: Patients will be followed up for 24 months, every 8 weeks.

Conditions

Small Cell Lung Cancer; Lung Cancer

Keywords

small cell lung cancer; lung cancer; ED-SCLC; Thoracic radiotherapy; Durvalumab; extensive-stage disease small cell lung cancer; Prospective; multicenter; single-arm; phase II trial; open-label; Carboplatin; Etoposide

Outcome Measures

Primary Outcomes (1)

• Progression-free rate (PFR) (RECIST v.1.1)

  PFR (RECIST v.1.1) at 12 months after registration, defined by the Kaplan-Meier estimator for progression-free survival (RECIST v.1.1) at 12 months (+ 4 weeks as we allow 4 weeks delay in the tumor assessment at 12 months).

  at 12 months after registration

Secondary Outcomes (7)

• Progression-free survival (PFS) (RECIST v.1.1)

  From the date of registration until the date of progressive disease according to RECIST v1.1 or death, whichever occurs first, assessed up to 4 years after registration.

• Progression-free survival (PFS) (RECIST v.1.1) outside the brain

  From the date of registration until the date of progressive disease according to RECIST v1.1 or death, whichever occurs first, assessed up to 4 years after registration

• Progression-free survival (RECIST v.1.1) after induction chemotherapy (PFS-IND)

  From the date of completion of induction chemotherapy until the date of progressive disease according to RECIST v1.1 or death, whichever occurs first, assessed up to 4 years after registration

• Overall Survival (OS)

  From the date of registration until the date of death, assessed up to 4 years after registration

• Objective response rate (ORR)

  From the date of registration until the date of progressive disease according to RECIST v1.1 or death, whichever occurs first, assessed up to 4 years after registration

Study Arms (1)

Durvalumab & thoratic radiotherapy

EXPERIMENTAL

Patients will start with an induction phase (part 1). Patients with CR; PR or SD after the induction phase, will transfer to the maintenance phase (part 2). Patients with PD after the induction phase will transfer to the follow-up phase. Induction phase (part 1): Patients will receive durvalumab in combination with carboplatin and etoposide for 4 cycles of 21 days: Maintenance phase (part 2): Patients will receive durvalumab treatment up to PD or max. 2 years, i.e. 26 maintenance cycles, in combination with tRT: Follow up phase: Patients will be followed up for 24 months, every 8 weeks.

Drug: Durvalumab; Drug: carboplatin; Drug: etoposide; Radiation: Thoracic radiotherapy

Interventions

Durvalumab DRUG

Durvalumab: 1500 mg iv

Also known as: MEDI4736

Durvalumab & thoratic radiotherapy

carboplatin DRUG

Carboplatin: AUC 5 mg/mL/min iv

Durvalumab & thoratic radiotherapy

etoposide DRUG

Etoposide: 100 mg/m2 iv

Durvalumab & thoratic radiotherapy

Thoracic radiotherapy RADIATION

Thoracic radiotherapy: 39 Gy in 13 fractions, starting 3-8 weeks after day 1 of last cycle of induction treatment, over 2.5 weeks Prophylactic cranial irradiation (PCI) is allowed but optional: according to local practice, starting 3-8 weeks after day 1 of last cycle of induction treatment Follow up phase Patients will be followed up for 24 months, every 8 weeks.

Durvalumab & thoratic radiotherapy

Eligibility Criteria

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

You may qualify if:

• Written informed consent according to Swiss law and ICH-GCP E6(R2) regulations before registration and prior to any trial specific procedures
• Histologically or cytologically1 confirmed extensive disease stage IV SCLC (T any, N any, M1 a/b) or T3-4 due to multiple lung nodules that are too extensive or have tumor/nodal volume that is too large to be encompassed in a tolerable radiation plan (according to American Joint Committee on Cancer Stage (8th edition)
• Patients must be considered suitable to receive carboplatin with etoposide as 1st line treatment for the ED-SCLC
• Patients with brain metastases are also eligible provided they are asymptomatic or treated central nervous system metastases and meet the following criteria:
• No ongoing requirement for corticosteroids at least 2 weeks prior to trial treatment
• No leptomeningeal disease
• Patients with a prior malignancy other than SCLC and treated with curative intention are eligible, if all treatment of that malignancy was completed at least 2 years before registration and the patient has no evidence of disease at registration. Less than 2 years is acceptable for malignancies with low risk of recurrence and/or no late recurrence, after consultation with the Coordinating Investigator
• Measurable disease per RECIST v1.1
• Age ≥ 18 years
• WHO performance status 0-1
• Adequate pulmonary function: forced expiratory volume in one second FEV (1) ≥ 1.0 liter
• Adequate bone marrow function:
• Absolute neutrophil count ≥ 1.5 x 109/L1
• Platelet count ≥ 100 x 109/L
• Hemoglobin ≥ 90 g/L

You may not qualify if:

• Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for ≥ 1 week prior to registration
• Prior chemotherapy treatment for ED-SCLC
• Any history of radiotherapy to the chest. Radiation therapy outside of the chest for palliative care (i.e., bone metastasis) is allowed but must be completed before first dose of -
• Prior systemic treatment including immune checkpoint inhibitors against SCLC
• Concomitant treatment within 30 days of registration with any other experimental drug and/or enrollment in another clinical trial
• Concomitant use of other anti-cancer drugs or radiotherapy. Except surgery for local pain control
• Severe or uncontrolled cardiovascular disease
• Congestive heart failure NYHA III or IV;
• Unstable angina pectoris
• History of myocardial infarction within the last 3 months
• Serious arrhythmias requiring medication (with exception of atrial fibrillation or paroxysmal supraventricular tachycardia)
• Uncontrolled hypertension
• Uncontrolled or symptomatic hypercalcemia, i.e.
• \> 1.5 mmol/L ionized calcium
• \> 12 mg/dL or \> 3 mmol/L corrected serum calcium

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (14)

Kantonsspital Aarau

Aarau, CH-5001, Switzerland

Location

Universitaetsspital Basel

Basel, 4031, Switzerland

Location

IOSI Ospedale Regionale di Bellinzona e Valli

Bellinzona, 6500, Switzerland

Location

Inselspital Bern

Bern, 3010, Switzerland

Location

Kantonsspital Graubuenden

Chur, CH-7000, Switzerland

Location

Hôpitaux Universitaires de Genève

Geneva, 1211, Switzerland

Location

Klinik Hirslanden

Männedorf, 8708, Switzerland

Location

Spital Männedorf

Männedorf, 8708, Switzerland

Location

Kantonsspital Olten

Olten, CH-4600, Switzerland

Location

Kantonsspital - St. Gallen

Sankt Gallen, CH-9007, Switzerland

Location

Regionalspital Thun

Thun, 3600, Switzerland

Location

HFR Freiburg - Kantonsspital

Villars-sur-Glâne, 1752, Switzerland

Location

Kantonsspital Winterthur

Winterthur, 8401, Switzerland

Location

UniversitätsSpital Zürich

Zurich, 8091, Switzerland

Location

MeSH Terms

Conditions

Small Cell Lung Carcinoma; Lung Neoplasms

Interventions

durvalumab; Carboplatin; Etoposide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Study Officials

• Alfredo Addeo, Prof

  Hôpitaux Universitaires Genève

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a prospective, multicenter, open-label, single-arm, phase II trial

Study Record Dates

• First Submitted: July 10, 2020
• First Posted: July 16, 2020
• Study Start: June 25, 2021
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: October 1, 2025

Record last verified: 2025-09

Locations

CH (14)