PACCELIO - FDG-PET Based Small Volume Accelerated Immuno Chemoradiotherapy in Locally Advanced NSCLC

NCT06102057 | Recruiting Phase 2 DMC

• 3 other identifiers: ESR-21-215362022-003408-33ARO 2023-06
• Study Type: interventional
• Target: 110
• Locations: 2 countries
• Sites: 11

Brief 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.

Conditions

Locally Advanced; Unresectable; Stage III Non-small Cell Lung Cancer

Keywords

chemoradiotherapy; immunotherapy; small volume accelerated chemoradiotherapy

Outcome Measures

Primary Outcomes (1)

• Comparison of the Completion rate of Experimental Arm to Conventional Arm

  To assess the feasibility of an FDG-PET-based small volume accelerated chemoradiotherapy followed by immunotherapy with durvalumab compared to standard FDG-PET-based chemoradiotherapy followed by immunotherapy with durvalumab Completion rate defined as rate of patients having received: * the prescribed radiotherapy dose ± 2 fractions and * simultaneous platinum-based chemotherapy and · immunotherapy consolidation with durvalumab starting within 42 days after the last dose of chemoradiotherapy and * either at least 3 doses of durvalumab or less than 3 doses of durvalumab in case immunotherapy was permanently discontinued due to documented extrathoracic immune-related toxicity.

  approximately 22 weeks after start of radio-chemotherapy

Secondary Outcomes (13)

• Comparison of the Occurrence of adverse events and serious events of Experimental Arm to Conventional Arm

  up to 78 weeks

• Comparison of the Time to locoregional progression of Experimental Arm to Conventional Arm

  time from randomization to progression in the primary tumor or any of mediastinal lymph nodes, up to 143,5 weeks

• Comparison of the Time to locoregional in-RT-field progression of Experimental Arm to Conventional Arm

  time from rando to progression in primary tumor or mediastinal lymph nodes within the target volume, up to 143,5 weeks

• Comparison of the Time to locoregional out-of-RT-field progression of Experimental Arm to Conventional Arm

  time from rando to progression in mediastinal lymph nodes outside the target volume, up to 143,5 weeks

• Comparison of the Time to distant progression time from rando to appearance of metastases elsewhere of Experimental Arm to Conventional Arm

  time from rando to appearance of metastases elsewhere, up to 143,5 weeks

Other Outcomes (9)

• To exploratively analyze the impact of lesional FDG uptake in baseline PET/CT as predictive factor for response to radio-chemo-immunotherapy, PFS, and survival

  time from randomization to disease progression or death by any cause, up to 143,5 weeks

• To exploratively analyze anatomic (RECIST)/metabolic (PERCIST) response to chemoradiotherapy in FDG-PET/CT at the end of chemoradiotherapy as predictive factor for overall response, response to consolidating immunotherapy, PFS, and survival

  time from randomization to disease progression or death by any cause, up to 143,5 weeks

• Exploratively evaluate add.effect of consolidation immunotherapy measured 3 months after the end of CRT on metabolic response beyond that measured at the end of CRT, further PFS and survival as potential hint for necessary treatment intensification

  time from randomization to disease progression or death by any cause, up to 143,5 weeks

Study Arms (2)

Conventional Arm

ACTIVE COMPARATOR

standard FDG-PET-based radiotherapy with concurrent standard of care chemotherapy

Radiation: standard Radiotherapy; Drug: Chemotherapy; Drug: Immunotherapy

Experimental Arm

EXPERIMENTAL

FDG-PET-based small volume accelerated radiotherapy with concurrent standard of care chemotherapy

Drug: Chemotherapy; Drug: Immunotherapy; Radiation: Experimental Radiotherapy

Interventions

Immunotherapy DRUG

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.

Also known as: standard

Conventional Arm; Experimental Arm

Experimental Radiotherapy RADIATION

FDG-PET-based small volume accelerated radiotherapy

Also known as: Experimental

Experimental Arm

standard Radiotherapy RADIATION

standard FDG-PET-based radiotherapy

Also known as: standard

Conventional Arm

Chemotherapy DRUG

concurrent standard of care chemotherapy

Also known as: standard

Conventional Arm; Experimental Arm

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
• 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

You may not qualify if:

• 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:

Sponsors & Collaborators

• AstraZeneca: collaborator
• TheraOp: lead

Study Sites (11)

Universitätsklinik Carl Gustav Carus der Technischen Universität Dresden

Dresden, 01307, Germany

RECRUITING

Universitätsklinikum Essen - Klinik für Strahlentherapie

Essen, 45122, Germany

NOT YET RECRUITING

Medical Center - University Of Freiburg, Department of Radiation Oncology

Freiburg im Breisgau, 79106, Germany

RECRUITING

Universitätsmedizin Göttingen, Department for Radiotherapy and Radiooncology

Göttingen, 37075, Germany

RECRUITING

Universität des Saarlandes, Klinik für Strahlentherapie und Radioonkologie

Homburg, 66421, Germany

RECRUITING

Kliniken Maria Hilf GmbH Mönchengladbach

Mönchengladbach, 41063, Germany

RECRUITING

Klinikum der Universitaet Muenchen AöR, Department of Radiotherapy and Radiation Oncology

München, 81377, Germany

RECRUITING

Pius-Hospital Oldenburg, Hematology and Oncology

Oldenburg, 26121, Germany

RECRUITING

Vinzenz Von Paul Kliniken gGmbH, Klinik für Strahlentherapie und Palliativmedizin

Stuttgart, 70199, Germany

RECRUITING

Überörtliche Berufsausübungsgemeinschaft Troisdorf

Troisdorf, 53840, Germany

RECRUITING

Universitätsspital Zürich

Zurich, 8091, Switzerland

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Drug Therapy; Immunotherapy

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; Immunomodulation; Biological Therapy

Study Officials

• Ursula Nestle, Prof.

  Kliniken Maria Hilf GmbH

  PRINCIPAL INVESTIGATOR

• Stefan Rieken, Prof.

  Universitätsmedizin Göttingen (UMG)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bernhard Remes, Dr.

CONTACT

+49 641 944 36 36; paccelio@theraop.de

Sascha Herzer

CONTACT

+49 641 944 36 36; sahe@alcedis.de

Study Design

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

Model Details: 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)

Study Record Dates

• First Submitted: September 8, 2023
• First Posted: October 26, 2023
• Study Start: July 1, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2028
• Last Updated: December 17, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

DE (10); CH (1)