PACCELIO - FDG-PET based small volume accelerated immuno chemoradio-therapy in locally advanced NSCLC

Overview

Sponsor-declared trial summary

Key facts

Sponsor

TheraOp gGmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

15 Apr 2024 → ongoing

Decision date (initial)

2024-07-30

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-510506-41-00

EudraCT number

2022-003408-33

ClinicalTrials.gov

NCT06102057

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Safety, Therapy, Efficacy

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

Secondary objectives 4

1. - To assess the safety and tolerability of an FDG-PET-based small volume accelerated chemoradiotherapy followed by immunotherapy with durvalumab
2. - 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
3. - 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 chemoradiotherapy followed by immunotherapy with durvalumab
4. For more information please refer to the most current study protocol (chapter 2)

Conditions and MedDRA coding

Locally advanced, unresectable non-small-cell lung cancer (NSCLC) (Stage III) with a PD-L1-expression of ≥ 1%

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

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 folliclestimulating 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

Exclusion criteria 25

1. Mixed small cell and NSCLC histology
2. Neuroendocrine tumour, except of large cell neuroendocrine carcinoma of the lung
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) Basal cell carcinoma of the Skin b) Second malignancy diagnosed > 2 years prior to NSCLC diagnosis if after curative treatment without persistence or progression at baseline. 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. c) Adequately treated non-melanoma skin cancer or lentigo maligna without evi-dence of disease d) 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Completion rate defined as rate of patients having received: • the prescribed radiotherapy dose ± 2 fractions and
2. simultaneous platinum-based chemotherapy and
3. immunotherapy consolidation with durvalumab starting within 42 days after the last dose of chemoradiotherapy and
4. 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.

Secondary endpoints 11

1. Safety endpoints: Adverse events grade ≥ 3 (according to NCI CTCAE v5.0), SAEs, unexpected AEs
2. Efficacy endpoints: • Time to locoregional progression: time from randomization to progression in the primary tumor or any of mediastinal lymph nodes
3. 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
4. Time to locoregional out-of-RT-field progression: time from randomization to progression in mediastinal lymph nodes outside the target volume
5. Time to distant progression: time from randomization to appearance of metasta-ses elsewhere
6. Progression-free survival (PFS)
7. Overall survival (OS)
8. Objective response rate (ORR) defined as the proportion of randomized patients with best response of complete or partial response
9. Disease control rate (DCR) defined as the proportion of randomized patients with best response of complete response, partial response, or stable disease
10. Quality of Life: EORTC QLQ-C30 and QLQ-LC13: Change in symptoms, functioning, and global healthstatus/QoL
11. Radiotherapy quality: Percentage of patients without major proto-col deviations regarding radiotherapy quality

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

TheraOp gGmbH

Sponsor organisation

TheraOp gGmbH

Address

Winchester Strasse 3

City

Giessen

Postcode

35394

Country

Germany

Scientific contact point

Organisation

TheraOp gGmbH

Contact name

Bernhard Remes

Public contact point

Organisation

TheraOp gGmbH

Contact name

Bernhard Remes

Third parties 1

Locations

1 EU/EEA country · 10 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications