Strona Badania kliniczne Nct

Summary
EudraCT Number:2022-003408-33
Sponsor's Protocol Code Number:ESR-21-21536
National Competent Authority:Germany - PEI
Clinical Trial Type:EEA CTA
Trial Status:Ongoing
Date on which this record was first entered in the EudraCT database:2022-12-02
Trial results
A. Protocol Information
A.1Member State ConcernedGermany - PEI
A.2EudraCT number2022-003408-33
A.3Full title of the trial
PACCELIO - FDG-PET based small volume accelerated immuno chemoradio-therapy in locally advanced NSCLC
A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
Treating patients with locally advanced, unresectable non-small-cell lung cancer with a small volume accelerated chemoradiotherapy followed by immunotherapy with durvalumab
A.3.2Name or abbreviated title of the trial where available
PACCELIO
A.4.1Sponsor's protocol code numberESR-21-21536
A.7Trial is part of a Paediatric Investigation Plan No
A.8EMA Decision number of Paediatric Investigation Plan
B. Sponsor Information
B.Sponsor: 1
B.1.1Name of SponsorTheraOp gGmbH
B.1.3.4CountryGermany
B.3.1 and B.3.2Status of the sponsorNon-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1Name of organisation providing supportAstraZeneca GmbH
B.4.2CountryGermany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1Name of organisationTheraOp gGmbH
B.5.2Functional name of contact pointSascha Herzer
B.5.3 Address:
B.5.3.1Street AddressWinchester Straße 3
B.5.3.2Town/ cityGießen
B.5.3.3Post code35394
B.5.3.4CountryGermany
B.5.4Telephone number+4964194436256
B.5.5Fax number+496419443670
B.5.6E-mailpaccelio@theraop.de
D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation Yes
D.2.1.1.1Trade name IMFINZI®
D.2.1.1.2Name of the Marketing Authorisation holderAstraZeneca AB
D.2.1.2Country which granted the Marketing AuthorisationGermany
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.4Pharmaceutical form Concentrate for solution for infusion
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPIntravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNDurvalumab
D.3.9.1CAS number 1428935-60-7
D.3.9.4EV Substance CodeSUB176342
D.3.10 Strength
D.3.10.1Concentration unit mg milligram(s)
D.3.10.2Concentration typeequal
D.3.10.3Concentration number1500
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin No
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) Yes
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.8 Information on Placebo
E. General Information on the Trial
E.1 Medical condition or disease under investigation
E.1.1Medical condition(s) being investigated
Locally advanced, unresectable non-small-cell lung cancer (NSCLC) (Stage III) with a PD-L1-expression of ≥ 1%
E.1.1.1Medical condition in easily understood language
lung cancer
E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
MedDRA Classification
E.1.2 Medical condition or disease under investigation
E.1.2Version 21.1
E.1.2Level PT
E.1.2Classification code 10029519
E.1.2Term Non-small cell lung cancer stage III
E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
E.1.3Condition being studied is a rare disease No
E.2 Objective of the trial
E.2.1Main objective of the trial
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
E.2.2Secondary objectives of the trial
- To assess the safety and tolerability of an FDG-PET-based small volume accelerated chemoradiotherapy followed by immunotherapy with durvalumab
- To assess the efficacy 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 in terms of time to locoregional progression, time to locoregional in- and out-of-RT-field progression, time to distant progression, progression-free survival, overall survival, objective response rate, disease control rate
- To assess symptoms and patient-reported health-related quality of life (QoL) in patients receiving an FDG-PET-based small volume accelerated chemoradiotherapy followed by immunotherapy with durvalumab compared to patients receiving standard FDG-PET-based chemo-radiotherapy followed by immunotherapy with durvalumab

For more information please refer to the most current study protocol (chapter 2)
E.2.3Trial contains a sub-study No
E.3Principal inclusion criteria
1. Written informed consent
2. Patients irrespective of sex and gender, aged 18 years or older at the time of signing the ICF
3. 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
4. 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))
5. Patients fit for simultaneous chemoradiotherapy and consolidation immunotherapy according to interdisciplinary consensus
6. 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
7. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 at enrolment
8. Tumor assessment by FDG-PET CT within 21 days prior to start of chemoradiotherapy.
9. Adequate pulmonary function test results
a. Pre- or post-bronchodilator forced expiratory volume 1 of 1.0 L or >40% of predicted
AND
b. Diffusing capacity of the lung for carbon monoxide (DLCO) >30% of predicted
10. Adequate bone marrow and organ function at enrolment
a) Hemoglobin ≥9.0 g/dL
b) Absolute neutrophil count >1.5 × 109/L
c) Platelet count >100 × 109/L
d) Serum bilirubin ≤1.5 × upper limit of normal (ULN)
e) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN
f) Measured creatinine clearance (CrCl) >40 mL/min or calculated CL >40 mL/min as determined by Cockcroft-Gault (using actual body weight)
11. Body weight of >30 kg at enrolment
12. 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:
a. 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
b. 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, chemotherapy-induced menopause with >1 year interval since last menses, or surgical sterilization (bilateral oophorectomy or hysterectomy)
13. 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
E.4Principal exclusion criteria
1. Mixed small cell and NSCLC histology
2. Neuroendocrine tumour
3. Distant metastases
4. Malignant pleural effusion or pericardial effusion
5. Acute superior vena cava obstruction
6. Receipt of prior or current cancer treatment for NSCLC, including but not limited to, surgical resection, radiation therapy, investigational agents, hemotherapy, and mAbs. Exception: Prior surgical resection of limited metachronous NSCLC (i.e., stage I or II) is permitted.
7. 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
8. Major surgical procedure (as defined by the Investigator) within 28 days prior start of treatment.
9. 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
10. Current use of ongoing long-term immunosuppressive medication. The following are exceptions to this criterion
a. Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
b. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of pred-nisone or its equivalent
c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
11. History of allogeneic organ transplantation
12. 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:
a. Patients with vitiligo or alopecia
b. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
c. Any chronic skin condition that does not require systemic therapy
d. Patients without active disease in the last 5 years at randomization may be included but only after consultation with the local study physician
e. Patients with celiac disease controlled by diet alone
13. 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
14. Patients with oxygen dependence
15. Acute inflammation of mediastinal lymph nodes/mediastinal lymphadenopathy in the context of active pneumoconiosis, sarcoidosis or tuberculosis
16. History of another primary malignancy except for
a. 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.
b. Adequately treated non-melanoma skin cancer or lentigo maligna without evi-dence of disease
c. Adequately treated carcinoma in situ without evidence of disease
17. History of leptomeningeal carcinomatosis
18.Positive diagnostic test for hepatitis B (hepatitis B surface antigen) or hepatitis C (hepatitis C
antibody or hepatitis C RNA)
19. Known active infection of tuberculosis or human immunodeficiency virus
20. Known allergy or hypersensitivity to concomitant chemotherapy and durvalumab or any of the excipients
21. Any medical contraindication to treatment with platinum-based doublet chemotherapy as listed in the applying SmPCs
22. Patients who have disease considered for surgical treatment as part of their care plan, such as Pancoast or superior sulcus tumors.
23. Concurrent enrolment in another clinical study, unless it is an observational (noninterventional) clinical study or the follow-up period of an interventional study
24. Participation in another clinical study with an investigational product during the 4 weeks prior to enrolment
25. Pregnancy or breast-feeding
E.5 End points
E.5.1Primary end point(s)
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.

E.5.1.1Timepoint(s) of evaluation of this end point
approximately 22 weeks after start of radio-chemotherapy
E.5.2Secondary end point(s)
Safety endpoints:
Adverse events grade ≥ 3 (according to NCI CTCAE v5.0), SAEs, unexpected AEs

Efficacy endpoints:
• Time to locoregional progression: time from randomization to progression in the primary tumor or any of mediastinal lymph nodes
• Time to locoregional in-RT-field progres-sion: time from randomization to progres-sion in primary tumor or mediastinal lymph nodes within the target volume
• Time to locoregional out-of-RT-field progression: time from randomization to progression in mediastinal lymph nodes outside the target volume
• Time to distant progression: time from randomization to appearance of metasta-ses elsewhere
• Progression-free survival (PFS)
• Overall survival (OS)
• Objective response rate (ORR) defined as the proportion of randomized patients with best response of complete or partial response
• Disease control rate (DCR) defined as the proportion of randomized patients with best response of complete response, partial response, or stable disease

Quality of Life:
EORTC QLQ-C30 and QLQ-LC13: Change in symptoms, functioning, and global healthstatus/QoL

Radiotherapy quality:
Percentage of patients without major proto-col deviations regarding radiotherapy quality
E.5.2.1Timepoint(s) of evaluation of this end point
Safety Endpoints: during the whole study
PFS: time from randomization to disease progression or death by any cause
OS: time from randomization to death by any cause
ORR, DCR: end of study
Quality of Life: during whole study
Radiotherapy quality: during whole study
E.6 and E.7 Scope of the trial
E.6Scope of the trial
E.6.1Diagnosis No
E.6.2Prophylaxis No
E.6.3Therapy Yes
E.6.4Safety Yes
E.6.5Efficacy Yes
E.6.6Pharmacokinetic No
E.6.7Pharmacodynamic No
E.6.8Bioequivalence No
E.6.9Dose response Yes
E.6.10Pharmacogenetic No
E.6.11Pharmacogenomic No
E.6.12Pharmacoeconomic No
E.6.13Others No
E.7Trial type and phase
E.7.1Human pharmacology (Phase I) No
E.7.1.1First administration to humans No
E.7.1.2Bioequivalence study No
E.7.1.3Other No
E.7.1.3.1Other trial type description
E.7.2Therapeutic exploratory (Phase II) Yes
E.7.3Therapeutic confirmatory (Phase III) No
E.7.4Therapeutic use (Phase IV) No
E.8 Design of the trial
E.8.1Controlled Yes
E.8.1.1Randomised Yes
E.8.1.2Open Yes
E.8.1.3Single blind No
E.8.1.4Double blind No
E.8.1.5Parallel group Yes
E.8.1.6Cross over No
E.8.1.7Other No
E.8.2 Comparator of controlled trial
E.8.2.1Other medicinal product(s) No
E.8.2.2Placebo No
E.8.2.3Other Yes
E.8.2.3.1Comparator description
Standard FDG-PET-based radiotherapy with concurrent soc chemotherapy following immunotherapy
E.8.2.4Number of treatment arms in the trial2
E.8.3 The trial involves single site in the Member State concerned No
E.8.4 The trial involves multiple sites in the Member State concerned Yes
E.8.4.1Number of sites anticipated in Member State concerned10
E.8.5The trial involves multiple Member States Yes
E.8.5.1Number of sites anticipated in the EEA10
E.8.6 Trial involving sites outside the EEA
E.8.6.1Trial being conducted both within and outside the EEA Yes
E.8.6.2Trial being conducted completely outside of the EEA No
E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
Switzerland
E.8.7Trial has a data monitoring committee No
E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
Overall end of study will be reached 24 months after the last patient has started durvalumab therapy
E.8.9 Initial estimate of the duration of the trial
E.8.9.1In the Member State concerned years4
E.8.9.1In the Member State concerned months3
E.8.9.1In the Member State concerned days0
E.8.9.2In all countries concerned by the trial years4
E.8.9.2In all countries concerned by the trial months3
E.8.9.2In all countries concerned by the trial days0
F. Population of Trial Subjects
F.1 Age Range
F.1.1Trial has subjects under 18 No
F.1.1.1In Utero No
F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
F.1.1.3Newborns (0-27 days) No
F.1.1.4Infants and toddlers (28 days-23 months) No
F.1.1.5Children (2-11years) No
F.1.1.6Adolescents (12-17 years) No
F.1.2Adults (18-64 years) Yes
F.1.2.1Number of subjects for this age range: 55
F.1.3Elderly (>=65 years) Yes
F.1.3.1Number of subjects for this age range: 55
F.2 Gender
F.2.1Female Yes
F.2.2Male Yes
F.3 Group of trial subjects
F.3.1Healthy volunteers No
F.3.2Patients Yes
F.3.3Specific vulnerable populations Yes
F.3.3.1Women of childbearing potential not using contraception No
F.3.3.2Women of child-bearing potential using contraception Yes
F.3.3.3Pregnant women No
F.3.3.4Nursing women No
F.3.3.5Emergency situation No
F.3.3.6Subjects incapable of giving consent personally No
F.3.3.7Others No
F.4 Planned number of subjects to be included
F.4.1In the member state100
F.4.2 For a multinational trial
F.4.2.1In the EEA 100
F.4.2.2In the whole clinical trial 110
F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
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.
G. Investigator Networks to be involved in the Trial
N. Review by the Competent Authority or Ethics Committee in the country concerned
N.Competent Authority Decision Authorised
N.Date of Competent Authority Decision2023-01-12
N.Ethics Committee Opinion of the trial applicationFavourable
N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
N.Date of Ethics Committee Opinion2023-04-25
P. End of Trial
P.End of Trial StatusOngoing
3