PD-(L)1 iNhibitors with concurrent IRadiation at VAried tumour sites in advanced Non-small cell lung cAncer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Unicancer

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

21 Mar 2019 → ongoing

Decision date (initial)

2024-10-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

INCa

External identifiers

EU CT number

2024-512173-27-00

EudraCT number

2017-005142-29

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

To compare Overall Survival (OS) rate between anti-PD-1 and chemotherapy versus anti-PD-1 and chemotherapy + radiotherapy with report of 1 year-rate.

Secondary objectives 10

1. To compare between the two arms: Toxicities according to CTCAE v5
2. To compare between the two arms: Tumour response according to RECIST 1.1 and iRECIST (centralized response evaluation)
3. To compare between the two arms: Overall Survival (OS) with report of 2 year-rate
4. To compare between the two arms: Progression Free Survival (PFS) with report of 1 year-rate.
5. To compare between the two arms: Cancer Specific Survival (CSS) with report of 1 year-rate.
6. To compare between the two arms: To compare between the two arms: In irradiated patients: local and distant control with report of 6 months and 1-year rates in irradiated and non-irradiated sites, respectively.
7. To compare between the two arms: Quality of life according to QLQ-C30.
8. To compare : Best tumour response between arms, local and distant control according to RECIST 1.1 and iRECIST (centralized response evaluation) on irradiated and non-irradiated sites
9. To compare : Best tumour response between arms,
10. To compare : iPFS between arms.

Conditions and MedDRA coding

Advanced (stage IIIB/IIIC/IV) NSCLC patients eligible for treatment with a PD-1 antagonist (pembrolizumab) according to the European Marketing Authorisation in a first line

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Patient must have signed a written informed consent form prior to any study specific procedures
2. Histologically or cytologically confirmed advanced (stage IIIB/IIIC/IV), squamous or non-squamous NSCLC
3. NSCLC patients eligible for treatment with pembrolizumab and chemotherapy according to the European Marketing Authorization: a. squamous: in combination with carboplatin and either paclitaxel or nab-paclitaxel ; b. non squamous with no EGFR or ALK positive mutations: in combination with pemetrexed and a platinum based chemotherapy
4. Patient ≥18 years of age.
5. ECOG performance status 0 – 1
6. Life expectancy >3 months
7. Measurable lesion as assessed by RECIST version 1.1.
8. Metastases and/or primary tumour eligible for 3 dimensional conventional radiotherapy (3D-CRT) or stereotactic ablative radiotherapy (SABR) in terms of dose constraints at organ at risk (according to QUANTEC review)
9. Patients must have adequate organ function defined by the following laboratory results obtained within 14 days prior to the first study treatment: a. absolute neutrophil count of ≥1 500 /mm3, b. platelets ≥ 100 000/mm3, c. haemoglobin >9 g/dL (transfusions allowed), d. creatinine clearance >60 mL/min e. bilirubin ≤1.5 X ULN (unless Gilbert’s syndrome where 3 X ULN is permitted) f. serum ALT and AST ≤2.5 X ULN (unless documented liver metastasis where ≤5 X ULN is permitted) g. ALP ≤2.5 X ULN (unless documented bone or liver metastasis where ≤5X ULN is permitted). h. INR , PT, PTT ≤1.5 X ULN (unless the subject is receiving anticoagulant therapy)
10. Woman of childbearing potential and male patients must agree to use adequate contraception for the duration of study participation and up to 6 months after completing treatment/therapy
11. Patients affiliated to the social security system (or equivalent).
12. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits, and examinations including follow-up.

Exclusion criteria 24

1. Non-squamous NSCLC with targetable tumor mutations, activating EGFR mutations or ALK translocation.
2. Stage IIIB/IIIC NSCLC patient eligible to curative (thoracic radiotherapy or surgery) treatments in first line treatment.
3. Prior therapy with T-cell costimulation or checkpoint-targeted agents
4. Clinical need of radiotherapy (e.g.: whole brain irradiation, painful metastasis, bleeding, compressive metastases)
5. Irradiation within 2 months before inclusion.
6. Leptomeningeal carcinomatosis, or metastases with indistinct borders making targeting not feasible
7. Patient with evidence of active (presence of symptoms or requiring steroid treatment) central nervous system (CNS) metastases and/or carcinomatous meningitis. Patient with brain metastasis can be included if asymptomatic and not requiring steroids
8. Metastases located within 3 cm of the previously irradiated structures (EQD2doses): a. Spinal cord previously irradiated to >40 Gy; b. Brachial plexus previously irradiated to >50 Gy; c. Small intestine, large intestine, or stomach previously irradiated to >45 Gy; d. Brainstem previously irradiated to >50 Gy; e. Lung previously irradiated with prior V20Gy >30%
9. Active autoimmune disease except vitiligo, type-1 diabetes, hypothyroid stabilized with hormonal substitution, psoriasis
10. Symptomatic interstitial lung disease
11. Systemic immunosuppression or systemic immunosuppressive medicinal products within 2 weeks prior to study entry.
12. Concomitant treatment with steroids > 10 mg.
13. Prior invasive malignancy within the past 2 years (except non-melanomatous skin cancer non-invasive carcinoma in-situ of the breast, oral cavity, bladder or cervix)
14. Known Acquired Immune Deficiency Syndrome (AIDS) or severe uncontrolled co-morbidity
15. Known currently active infection including hepatitis B and hepatitis C
16. Patient who was administered a live, attenuated vaccine within 28 days prior to enrolment
17. Patient with any other disease or illness that requires hospitalisation or is incompatible with the study treatment are not eligible. Patient unable to comply with study obligations for geographic, social, or physical reasons, or who is unable to understand the purpose and procedures of the study
18. Patient who have taken any investigational medicinal product or have used an investigational device within 30 days of inclusion
19. Pregnant or breast feeding woman
20. Person deprived of their liberty or under protective custody or guardianship.
21. If pemetrexed: patient is unable or unwilling to take folic acid or vitamin B12 supplementation
22. Pre-existing peripheral neuropathy of a severity of grade ≥ 2 by NCI CTCAE v5.0.
23. Known hypersensitivity to one of the compounds or substances used in this protocol.
24. Major surgery within the 28 days before initiating study treatment

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint of this trial is overall survival (OS) defined as the time from randomization to the date of documented death from any cause or last follow-up. OS rate will be reported at 1 year.

Secondary endpoints 7

1. Acute/ late toxicity will be assessed according to the flowchart and graded by CTCAE v5 (toxic death and serious adverse events)
2. Tumour response is defined as the percentage of patients with a complete response (CR) or partial response (PR), according to RECIST 1.1 and iRECIST (centralized response evaluation).
3. Overall survival (OS) is defined as the time from randomization to the date of documented death from any cause or last follow-up. OS rate will be reported at 2 years.
4. Progression-free survival (PFS) or iPFS [Seymour, 2017] are defined as the time from randomization until documented disease progression (PD) according to RECIST 1.1 and iRECIST (centralized response evaluation for both arms), or death, or last follow-up for patient alive whichever occurs first. PFS rate will be reported at 1 year.
5. Cancer specific survival (CSS) is defined as the time from randomization to documented death from cancer from the treatment. CSS rate will be reported at 1 year.
6. Local and distant controls in irradiated patients are defined as the time from randomization to the first documented loco-regional event or distant event. Control rates will be reported at 6 months and 1 year
7. Quality of life will be assessed using self-administered questionnaires (EORTC QLQ-C30) according to the flowchart.

Investigational products

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

Test 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Unicancer

Sponsor organisation

Unicancer

Address

101 Rue De Tolbiac

City

Paris

Postcode

75013

Country

France

Scientific contact point

Organisation

Unicancer

Contact name

Nourredine AIT RAHMOUNE

Public contact point

Organisation

Unicancer

Contact name

Nourredine AIT RAHMOUNE

Locations

1 EU/EEA country · 37 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 10 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