Trial Title:
PACCELIO - FDG-PET Based Small Volume Accelerated Immuno Chemoradiotherapy in Locally Advanced NSCLC
NCT ID:
NCT06102057
Condition:
Stage III Non-small Cell Lung Cancer
Locally Advanced
Unresectable
Conditions: Official terms:
Carcinoma, Non-Small-Cell Lung
Immunomodulating Agents
Conditions: Keywords:
chemoradiotherapy
immunotherapy
small volume accelerated chemoradiotherapy
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Experimental Arm (FDG-PET-based small volume accelerated radiotherapy with concurrent
standard of care chemotherapy) Conventional Arm (standard FDG-PET-based radiotherapy with
concurrent standard of care chemotherapy)
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Radiation
Intervention name:
standard Radiotherapy
Description:
standard FDG-PET-based radiotherapy
Arm group label:
Conventional Arm
Other name:
standard
Intervention type:
Drug
Intervention name:
Chemotherapy
Description:
concurrent standard of care chemotherapy
Arm group label:
Conventional Arm
Arm group label:
Experimental Arm
Other name:
standard
Intervention type:
Drug
Intervention name:
Immunotherapy
Description:
standard of care consolidation therapy with durvalumab (fixed dose of 1500 mg q4w) for up
to 12 months or until progression of disease, unacceptable toxicity, patient´s wish, or
investigator´s decision, whichever comes first.
Arm group label:
Conventional Arm
Arm group label:
Experimental Arm
Other name:
standard
Intervention type:
Radiation
Intervention name:
Experimental Radiotherapy
Description:
FDG-PET-based small volume accelerated radiotherapy
Arm group label:
Experimental Arm
Other name:
Experimental
Summary:
Multinational, randomized, controlled, open-label, multicenter phase II trial. Eligible
patients will be randomized in a ratio of 1:1 to Experimental Arm (FDG-PET-based small
volume accelerated radiotherapy with concurrent standard of care chemotherapy) or
Conventional Arm (standard FDG-PET-based radiotherapy with concurrent standard of care
chemotherapy). Patients showing complete response, partial response, or stable disease
following chemoradiotherapy will receive standard of care consolidation therapy with
durvalumab (fixed dose of 1500 mg q4w) for up to 12 months or until progression of
disease, unacceptable toxicity, patient´s wish, or investigator´s decision, whichever
comes first.
After end of durvalumab therapy, patients will undergo safety follow up for 90 (+7) days
followed by survival follow up until overall end of study. Overall end of study will be
reached 24 months after the last patient has started durvalumab therapy. Patients showing
PD following chemoradiotherapy will be treated according to investigator´s decision but
will be followed up until overall end of study.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Written informed consent
- Patients irrespective of sex and gender, aged 18 years or older at the time of
signing the ICF
- Patients must be willing and able to comply with scheduled visits, treatment
schedule, laboratory testing, and other requirements of the study as determined by
the investigator
- Patients with histologically or cytologically documented NSCLC who present with
locally advanced, unresectable (Stage III) disease (according to version 8 of the
International Association for the Study of Lung Cancer Staging Manual in Thoracic
Oncology (IASLC Staging Manual in Thoracic Oncology 2016))
- Patients fit for simultaneous chemoradiotherapy and consolidation immunotherapy
according to interdisciplinary consensus
- Histologically proven PD-L1-expression of ≥ 1% (tumor proportion score; TPS) in
tumor sample as assessed in routine staging using a validated test such as Ventana
SP236 assay
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 at
enrolment
- Tumor assessment by FDG-PET CT within 21 days prior to start of chemoradiotherapy.
- Adequate pulmonary function test results
- Pre- or post-bronchodilator forced expiratory volume 1 of 1.0 L or >40% of
predicted AND
- Diffusing capacity of the lung for carbon monoxide (DLCO) >30% of predicted
- Adequate bone marrow and organ function at enrolment
- Hemoglobin ≥9.0 g/dL
- Absolute neutrophil count >1.5 × 109/L
- Platelet count >100 × 109/L
- Serum bilirubin ≤1.5 × upper limit of normal (ULN)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN
- Measured creatinine clearance (CrCl) >40 mL/min or calculated CL >40 mL/min as
determined by Cockcroft-Gault (using actual body weight)
- Body weight of >30 kg at enrolment
- Evidence of post-menopausal status, or negative urinary or serum pregnancy test for
female pre-menopausal patients. Women will be considered post-menopausal if they are
amenorrhoic for 12 months or more without an alternative medical cause. The
following age-specific requirements apply:
- Women <50 years old would be considered post-menopausal if they have been
amenorrhoic for 12 months or more following cessation of exogenous hormonal
treatments with luteinizing hormone and follicle-stimulating hormone levels in
the post-menopausal range for the institution
- Women ≥50 years old would be considered post-menopausal if they have been
amenorrhoic for 12 months or more following cessation of all exogenous hormonal
treatments, radiation-induced oophorectomy with last menses >1 year ago,
chemotherapyinduced menopause with >1 year interval since last menses, or
surgical sterilization (bilateral oophorectomy or hysterectomy)
- Women of childbearing potential (WOCBP) and male patients with partners of
childbearing potential must agree to always use a highly effective form of
contraception according to the Clinical Trials Facilitation and Coordination Group
during the treatment phase of this study and for at least 90 days after the last
dose durvalumab or 6 months after the last dose of chemotherapy, whichever occurs
last
Exclusion Criteria:
- Mixed small cell and NSCLC histology
- Neuroendocrine tumor
- Distant metastases
- Malignant pleural effusion or pericardial effusion
- Acute superior vena cava obstruction
- Receipt of prior or current cancer treatment for NSCLC, including but not limited
to, surgical resection, radiation therapy, investigational agents, chemotherapy, and
monoclonal antibodies (mAbs). Exception: Prior surgical resection of limited
metachronous NSCLC (i.e., stage I or II) is permitted.
- Receipt of live attenuated vaccine within 30 days prior to the start of therapy.
Note: Patients, if enrolled, should not receive live vaccine during treatment phase
and up to 30 days end of treatment
- Major surgical procedure (as defined by the Investigator) within 28 days prior start
of treatment.
- Prior exposure to immune-mediated therapy, including but not limited to, other
anti-CTLA-4, anti-PD-1, anti-PD-L1 (including durvalumab), and anti-PD-L2
antibodies, including therapeutic anticancer vaccines
- Current use of ongoing long-term immunosuppressive medication. The following are
exceptions to this criterion
- Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra
articular injection)
- Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of
prednisone or its equivalent
- Steroids as premedication for hypersensitivity reactions (e.g., CT scan
premedication)
- History of allogeneic 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, 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 at randomization may be
included but only after consultation with the local study physician
- Patients with celiac disease controlled by diet alone
- Uncontrolled intercurrent illness, including but not limited to, ongoing or active
infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
angina pectoris, cardiac arrhythmia, ILD, 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
- Patients with oxygen dependence
- Acute inflammation of mediastinal lymph nodes/mediastinal lymphadenopathy in the
context of active pneumoconiosis, sarcoidosis or tuberculosis
- History of another primary malignancy except for o Diagnosis of second malignancy
(except basal cell carcinoma) < 2 years prior to NSCLC diagnosis, or persistence or
progression of previously diagnosed malignancy.
Patients with a previous history of radiation therapy are eligible provided field overlap
is minimal and the risk of toxicity to tissues in the overlapping region(s) is deemed to
be acceptable by treating radiation oncologist.
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of
disease
- Adequately treated carcinoma in situ without evidence of disease
- History of leptomeningeal carcinomatosis
- Positive diagnostic test for hepatitis B (hepatitis B surface antigen) or
hepatitis C (hepatitis C antibody or hepatitis C RNA)
- Known active infection of tuberculosis or human immunodeficiency virus
- Known allergy or hypersensitivity to concomitant chemotherapy and durvalumab or
any of the excipients
- Any medical contraindication to treatment with platinum-based doublet
chemotherapy as listed in the applying SmPCs
- Patients who have disease considered for surgical treatment as part of their
care plan, such as Pancoast or superior sulcus tumors.
- Concurrent enrolment in another clinical study, unless it is an observational
(noninterventional) clinical study or the follow-up period of an interventional
study
- Participation in another clinical study with an investigational product during
the 4 weeks prior to enrolment
- Pregnancy or breast-feeding
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Medical Center - University Of Freiburg, Department of Radiation Oncology
Address:
City:
Freiburg
Zip:
79106
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Tanja Schimek-Jasch, Dr.
Facility:
Name:
Universitätsmedizin Göttingen, Department for Radiotherapy and Radiooncology
Address:
City:
Göttingen
Zip:
37075
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Rami El Shafie, Prof. Dr.
Facility:
Name:
Universität des Saarlandes, Klinik für Strahlentherapie und Radioonkologie
Address:
City:
Homburg
Zip:
66421
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Markus Hecht, Prof. Dr.
Facility:
Name:
Kliniken Maria Hilf GmbH Mönchengladbach
Address:
City:
Mönchengladbach
Zip:
41063
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Ursula Nestle, Prof. Dr.
Facility:
Name:
Klinikum der Universitaet Muenchen AöR, Department of Radiotherapy and Radiation Oncology
Address:
City:
München
Zip:
81377
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Eze Chukwuka, Dr.
Facility:
Name:
Pius-Hospital Oldenburg, Hematology and Oncology
Address:
City:
Oldenburg
Zip:
26121
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Frank Griesinger, Prof. Dr.
Facility:
Name:
Vinzenz Von Paul Kliniken gGmbH, Klinik für Strahlentherapie und Palliativmedizin
Address:
City:
Stuttgart
Zip:
70199
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Thomas Hehr, Prof. Dr.
Facility:
Name:
Universitätsspital Zürich
Address:
City:
Zürich
Zip:
8091
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Guckenberger Guckenberger, Prof. Dr.
Start date:
July 1, 2024
Completion date:
June 2028
Lead sponsor:
Agency:
TheraOp
Agency class:
Other
Collaborator:
Agency:
AstraZeneca
Agency class:
Industry
Source:
TheraOp
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06102057
