Durvalumab With Consolidative Radiochemotherapy and Ablative Stereotactic Radiotherapy in Oligometastatic ES-SCLC

NCT06223711 | Recruiting Phase 2 DMC

• 1 other identifier: DuCoRa-SCLC
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 5

Brief Summary

Open-label, single-arm, prospective multicenter phase II clinical trial to determine the efficacy of immunotherapy with durvalumab concomitant with radiochemotherapy, followed by durvalumab maintenance therapy in combination with stereotactic radiotherapy in extensive stage SCLC

Conditions

Extensive-stage Small-cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS) rate

  Efficacy of a treatment scheme consisting of thoracic radiotherapy concomitant to platinum/etoposide/durvalumab therapy followed by stereotactic radiotherapy concomitant to durvalumab maintenance to improve the one year PFS rate using investigator assessments according to RECIST 1.1

  12 month

Secondary Outcomes (1)

• overall survival (OS)

  12 month

Study Arms (1)

Treatment

EXPERIMENTAL

Thoracic Radiochemotherapy concomitant 2 cycles of etoposide/platinum + durvalumab Stereotactic radiotherapy of further tumor locations + durvalumab maintenance

Radiation: Thoracic Radiochemotherapy; Drug: durvalumab; Radiation: Stereotactic radiotherapy of further tumor locations; Drug: Chemotherapy

Interventions

Thoracic Radiochemotherapy RADIATION

Radiotherapy to the primary tumor including mediastinal lymph node metastases is delivered in single fractions of 1.8Gy once daily up to a cumulative dose of 63.0Gy by intensity modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT).

Treatment

durvalumab DRUG

Durvalumab is administered in fixed dose 1500mg in q3w cycles concomitant to chemotherapy and q4w cycles during maintenance treatment

Treatment

Stereotactic radiotherapy of further tumor locations RADIATION

Stereotactic radiotherapy is delivered to the up to four further tumor locations during durvalumab maintenance therapy and will be performed according to local standards with established dose and fractionation schemes in ablative doses depending on the affected organ system.

Treatment

Chemotherapy DRUG

Concomitant chemotherapy consists of further two cycles platinum/etoposide q3w (summarized cycle 3-4).

Treatment

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed first diagnosis of ES-SCLC according to the Veterans Administration Lung Study Group (VALG) Staging System for SCLC1 (disease extension that cannot be treated within one radiation field).
• Oligometastatic disease defined as follows:
• Primary tumor with or without mediastinal or supraclavicular lymph node metastases (counts as one lesion if it can be treated within one radiation field).
• Up to four distant tumor lesions/metastases that can be treated with stereotactic radiotherapy (stereotactic radiotherapy of lung metastases in addition to radiochemotherapy of primary tumor should previously be discussed with the principal investigator).
• No cytologically confirmed malignant pleural effusion (in case of suspected malignant pleural effusion in imaging, pleurocentesis for cytological assessment is required).
• Stable disease (SD) or partial response (PR) according to RECIST 1.1 criteria after previous treatment with two cycles of platinum/etoposide/durvalumab.
• Adequate lung function defined as forced expiratory volume in the first second (FEV1) ≥1.3 liter in spirometry.
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent including European Union Data Privacy Directive obtained from the patient prior to performing any protocol-related procedures, including screening evaluations.
• Age \> 18 years at time of study entry.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Body weight \>30 kg.
• Adequate normal organ and marrow function as defined below:
• Hemoglobin ≥9.0 g/dL
• White Blood Cells (WBC) ≥ 3,000 per mm3
• Platelet count \>100,000 per mm3

You may not qualify if:

• Participation in another clinical study with an investigational product during the last 4 weeks.
• Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
• Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician.
• Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
• Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug.
• Major surgical procedure (as defined by the investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
• History of allogenic organ transplantation.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease (e.g., colitis or Crohn's disease), diverticulitis (with the exception of diverticulosis), systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome (granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia
• Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
• Any chronic skin condition that does not require systemic therapy
• Patients without active disease in the last 5 years may be included but only after consultation with the study physician
• Patients with celiac disease controlled by diet alone
• Uncontrolled intercurrent illness, including but not limited to, ongoing or active symptomatic infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, QTcF (QT interval on ECG corrected using the Frederica's formula) \>470 ms, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.

Sponsors & Collaborators

• Universität des Saarlandes: lead

Study Sites (5)

University Hospital Augsburg, Radiation Oncology

Augsburg, Bavaria, 86156, Germany

RECRUITING

University Hospital Erlangen, Radiation Oncology

Erlangen, Bavaria, 91054, Germany

RECRUITING

University Hospital Regensburg, Clinic and Polyclinic for Radiotherapy

Regensburg, Bavaria, 93053, Germany

RECRUITING

Kliniken Maria Hilf

Mönchengladbach, North Rhine-Westphalia, 41063, Germany

RECRUITING

Saarland University Medical Center and Saarland University Faculty of Medicine, Clinic for Radiotherapy and Radiooncology

Homburg, Saarland, 66421, Germany

RECRUITING

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

durvalumab; Drug Therapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Therapeutics

Central Study Contacts

Wiebke Pirschel, M.Sc.

CONTACT

+49684116; wiebke.pirschel@uks.eu

Markus Hecht, Prof.

CONTACT

+49684116; markus.hecht.clinicaltrials@uks.eu

Study Design

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

Study Record Dates

• First Submitted: December 1, 2023
• First Posted: January 25, 2024
• Study Start: October 6, 2023
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: April 5, 2024

Record last verified: 2024-04

Locations

DE (5)