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

ConditionsStage III Non-small Cell Lung CancerLocally AdvancedUnresectable
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorTheraOp

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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))

Disqualifiers

Mixed small cell and NSCLC histology

Neuroendocrine tumor

Distant metastases

Malignant pleural effusion or pericardial effusion

Trial design

Design model

Parallel

Treatments tested in this trial

  • standard Radiotherapy

    Radiation

    standard FDG-PET-based radiotherapy

  • Chemotherapy

    Drug

    concurrent standard of care chemotherapy

  • 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.

  • Experimental Radiotherapy

    Radiation

    FDG-PET-based small volume accelerated radiotherapy

Treatment groups

110 Participants
are divided into 2 treatment groups
Group A: Conventional ArmActive comparator 3 interventions
Group B: Experimental ArmExperimental treatment 3 interventions

Trial outcomes

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.

Time frame
approximately 22 weeks after start of radio-chemotherapy

Secondary outcomes

1

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

To assess the safety and tolerability of an FDGPET- based small volume accelerated chemoradiotherapy followed by immunotherapy with durvalumab compared to standard FDG-PET-based chemoradiotherapy followed by immunotherapy with durvalumab Occurrence of adverse events and serious events: * adverse events grade ≥ 3 (according to NCI CTCAE v5.0) * SAEs * Unexpected AEs

Time frame
up to 78 weeks
2

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

Assess efficacy of FDG-PET-based smallvolumeaccelerated CRT followed by immunotherapy compared to standard FDG-PET-based CRT followed by immunotherapy in terms of time to locoreg. progression, time to locoreg. in- and out-of-RTfield progress \- Time to locoregional progression

Time frame
time from randomization to progression in the primary tumor or any of mediastinal lymph nodes, up to 143,5 weeks
3

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

Assess efficacy of FDG-PET-based smallvolumeaccelerated CRT followed by immunotherapy compared to standard FDG-PET-based CRT followed by immunotherapy in terms of time to locoreg. progression, time to locoreg. in- and out-of-RTfield progress · Time to locoregional in-RT-field progression

Time frame
time from rando to progression in primary tumor or mediastinal lymph nodes within the target volume, up to 143,5 weeks
4

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

Assess efficacy of FDG-PET-based smallvolumeaccelerated CRT followed by immunotherapy compared to standard FDG-PET-based CRT followed by immunotherapy in terms of time to locoreg. progression, time to locoreg. in- and out-of-RTfield progress · Time to locoregional out-of-RT-field progression

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

Other outcomes

1

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

Quantifiable imaging parameters (e.g., SUV) will be correlated to response and survival outcomes, reflected in separate protocol to be setup SUV is a common unitless measurement for radioactivity uptake. In the study we will measure maximum SUV and mean SUV from tumor volume. The tumor volume with the unit millilitre will be measured by an automatic segmentation were any area with SUV above a threshold value of 40% of SUVmax will be attributed to the tumor volume. These imaging parameters will be correlated with time to progression from randomization

Time frame
time from randomization to disease progression or death by any cause, up to 143,5 weeks
2

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

Quantifiable imaging parameters (e.g., SUV) will be correlated to response and survival outcomes, reflected in separate protocol to be setup SUV is a common unitless measurement for radioactivity uptake. In the study we will measure maximum SUV and mean SUV from tumor volume. The tumor volume with the unit millilitre will be measured by an automatic segmentation were any area with SUV above a threshold value of 40% of SUVmax will be attributed to the tumor volume. These parameters will be correlated with time to progression from randomization Also, for changes of measurements of SUVmax and SUVmax from baseline correlation will be done with time to progression. In this analyisis also changes in tumor diameter (measured from CT) and changes in tumor volume (measured from PET) will be included into the analysis.

Time frame
time from randomization to disease progression or death by any cause, up to 143,5 weeks
3

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

Quantifiable imaging parameters (e.g., SUV) will be correlated to response and survival outcomes, reflected in separate protocol to be setup SUV is a common unitless measurement for radioactivity uptake. In the study we will measure maximum SUV and mean SUV from tumor volume. The tumor volume with the unit millilitre will be measured by an automatic segmentation were any area with SUV above a threshold value of 40% of SUVmax will be attributed to the tumor volume. These imaging parameters will be correlated with time to progression from randomization Further changes of measurements of SUVmax, SUVmax, tumor diameter and tumor volume from end of chemoradiation therapy will be correlated with time to progression in the subgroup receiving three PET/CT scans.

Time frame
time from randomization to disease progression or death by any cause, up to 143,5 weeks
4

To exploratively analyze the impact of the neutrophil to lymphocyte ratio (NLR) as predictive biomarker for response to consolidating immunotherapy and survival

Relation of NLR to response and survival outcomes, reflected in separate protocol to be setup It is calculated by dividing the number of neutrophils by number of lymphocytes.

Time frame
up to 55 months

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

TheraOp

Lead sponsor

AstraZeneca

Collaborator

Source ClinicalTrials.gov
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