Trial Title:
Durvalumab With Consolidative Radiochemotherapy and Ablative Stereotactic Radiotherapy in Oligometastatic ES-SCLC
NCT ID:
NCT06223711
Condition:
Extensive-stage Small-cell Lung Cancer
Conditions: Official terms:
Small Cell Lung Carcinoma
Durvalumab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Radiation
Intervention name:
Thoracic Radiochemotherapy
Description:
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).
Arm group label:
Treatment
Intervention type:
Drug
Intervention name:
durvalumab
Description:
Durvalumab is administered in fixed dose 1500mg in q3w cycles concomitant to chemotherapy
and q4w cycles during maintenance treatment
Arm group label:
Treatment
Intervention type:
Radiation
Intervention name:
Stereotactic radiotherapy of further tumor locations
Description:
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.
Arm group label:
Treatment
Intervention type:
Drug
Intervention name:
Chemotherapy
Description:
Concomitant chemotherapy consists of further two cycles platinum/etoposide q3w
(summarized cycle 3-4).
Arm group label:
Treatment
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
Detailed description:
This is an open-label, prospective, multi-center single-arm phase II trial. Patients with
oligometastatic extensive stage SCLC will be enrolled in the trial. In this trial
oligometastatic disease is defined as up to five tumor lesions, whereas the primary tumor
including mediastinal lymph node metastases counts as one tumor lesion. The primary tumor
including lymph node metastases must be suitable for radiochemotherapy and all distant
metastases for stereotactic radiotherapy. Patients must have completed systemic therapy
with two cycles of platinum/etoposide/durvalumab and have stable disease or partial
response according to RECIST 1.1 criteria. After study inclusion, patients receive
radiochemotherapy with concomitant durvalumab (MEDI4736). Concomitant chemotherapy
consists of further two cycles platinum/etoposide q3w (summarized cycle 3-4). Dosing of
chemotherapy is etoposide 90mg/m² body surface area (BSA) day 1-3 in combination with
cisplatin 75mg/m² BSA on day 1 or carboplatin area under the curve (AUC) 5 mg/ml per
minute on day 1. Split dose of platinum chemotherapy to 2-3 days is an allowed treatment
option. Durvalumab is administered in fixed dose 1500mg in q3w cycles concomitant to
chemotherapy and q4w cycles during maintenance treatment. 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). In the following, stereotactic
radiotherapy is delivered to the up to four further tumor locations during durvalumab
maintenance therapy. Sequencing of radiotherapy of the primary tumor and metastases may
be changed if radiotherapy of brain, vertebral or other symptomatic metastases is
urgently necessary. Stereotactic radiotherapy will be performed according to local
standards with established dose and fractionation schemes in ablative doses depending on
the affected organ system.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
For inclusion in the study patients must fulfill all of the following criteria:
1. 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).
2. 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).
3. Stable disease (SD) or partial response (PR) according to RECIST 1.1 criteria after
previous treatment with two cycles of platinum/etoposide/durvalumab.
4. Adequate lung function defined as forced expiratory volume in the first second
(FEV1) ≥1.3 liter in spirometry.
5. 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.
6. Age > 18 years at time of study entry.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
8. Body weight >30 kg.
9. 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
- Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). This will not
apply to patients with confirmed Gilbert's syndrome (persistent or recurrent
hyperbilirubinemia that is predominantly unconjugated in the absence of
hemolysis or hepatic pathology), who will be allowed only in consultation with
their physician.
- AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal unless liver
metastases are present, in which case it must be ≤5x ULN
- Calculated creatinine CL>40 mL/min by the Cockcroft-Gault formula
10. Patient is willing and able to comply with the protocol for the duration of the
study including undergoing treatment and scheduled visits and examinations including
follow-up.
11. Must have a life expectancy of at least 12 weeks.
Exclusion Criteria:
Patients should not enter the study if any of the following exclusion criteria are
fulfilled:
1. Participation in another clinical study with an investigational product during the
last 4 weeks.
2. 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.
3. Prior systemic anticancer therapy (chemotherapy, immunotherapy, targeted therapy),
apart from two cycles of etoposide/platinum + durvalumab (prior chemotherapy/
immunotherapy/ targeted therapy for other malignancy treated with curative intent ≥5
years ago is no exclusion criterion).
4. Any unresolved toxicity NCI CTCAE Grade ≥2 from previous chemo-immunotherapy (2
cycles of platinum/etoposide + durvalumab) with the exception of alopecia, vitiligo,
and the laboratory values defined in the inclusion criteria
1. Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis
after consultation with the Study Physician.
2. Patients with irreversible toxicity not reasonably expected to be exacerbated
by treatment with durvalumab may be included only after consultation with the
Study Physician.
5. 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.
6. 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.
7. 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.
8. History of allogenic organ transplantation.
9. 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:
1. Patients with vitiligo or alopecia
2. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on
hormone replacement
3. Any chronic skin condition that does not require systemic therapy
4. Patients without active disease in the last 5 years may be included but only
after consultation with the study physician
5. Patients with celiac disease controlled by diet alone
10. 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.
11. History of another primary malignancy except for
1. Malignancy treated with curative intent and with no known active disease ≥5
years before the first dose of IP and of low potential risk for recurrence
2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
of disease
3. Adequately treated carcinoma in situ without evidence of disease
12. History of leptomeningeal carcinomatosis.
13. History of active primary immunodeficiency.
14. Known active hepatitis infection, positive hepatitis C virus (HCV) antibody,
hepatitis B virus (HBV) surface antigen (HBsAg) or HBV core antibody (anti-HBc), at
screening. Participants with a past or resolved HBV infection (defined as the
presence of anti HBc and absence of HBsAg) are eligible. Participants positive for
HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
15. Known to have tested positive for human immunodeficiency virus (HIV) (positive HIV
1/2 antibodies) or active tuberculosis infection (clinical evaluation that may
include clinical history, physical examination and radiographic findings).
16. Current or prior use of immunosuppressive medication within 14 days before the first
dose of durvalumab. The following are exceptions to this criterion:
1. Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra
articular injection)
2. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of
prednisone or its equivalent
3. Steroids as premedication for hypersensitivity reactions (e.g., CT scan
premedication)
17. Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.
Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and
up to 30 days after the last dose of IP.
18. Female patients who are pregnant or breastfeeding or male or female patients of
reproductive potential who are not willing to employ effective birth control from
screening to 90 days after the last dose of durvalumab monotherapy.
19. Known allergy or hypersensitivity to any of the study drugs or any of the study drug
excipients.
20. Prior randomization or treatment in a previous durvalumab clinical study regardless
of treatment arm assignment.
21. Judgment by the investigator that the patient is unsuitable to participate in the
study and the patient is unlikely to comply with study procedures, restrictions and
requirements.
22. Known allergy or hypersensitivity to IP or any excipient.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University Hospital Augsburg, Radiation Oncology
Address:
City:
Augsburg
Zip:
86156
Country:
Germany
Status:
Recruiting
Facility:
Name:
University Hospital Erlangen, Radiation Oncology
Address:
City:
Erlangen
Zip:
91054
Country:
Germany
Status:
Recruiting
Facility:
Name:
University Hospital Regensburg, Clinic and Polyclinic for Radiotherapy
Address:
City:
Regensburg
Zip:
93053
Country:
Germany
Status:
Recruiting
Facility:
Name:
Kliniken Maria Hilf
Address:
City:
Mönchengladbach
Zip:
41063
Country:
Germany
Status:
Recruiting
Facility:
Name:
Saarland University Medical Center and Saarland University Faculty of Medicine, Clinic for Radiotherapy and Radiooncology
Address:
City:
Homburg
Zip:
66421
Country:
Germany
Status:
Recruiting
Start date:
October 6, 2023
Completion date:
December 2027
Lead sponsor:
Agency:
Universität des Saarlandes
Agency class:
Other
Source:
Universität des Saarlandes
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06223711
