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Efecto de la inmunoterapia en pacientes con cáncer de pulmón de células no pequeñas oligometastásico (número limitado de metástasis) después de haber sido tratados con radioterapia y/o cirugía

Phase 2/3
Recruiting
Conditions
Non-small cell lung cancer
Registration Number
2023-508741-40-00
Lead Sponsor
European Organisation For Research And Treatment Of Cancer
Brief Summary

To assess whether continuation of cemiplimab treatment (for up to 12 months) increases progression free survival (PFS) as compared to placebo in patients with stage IV, synchronous, oligometastatic NSCLC who have not progressed following 4 cycles of platinum-based chemotherapy plus cemiplimab or cemiplimab alone and who received a radical treatment (primary tumour and metastases) if a complete response was not achieved.

Detailed Description

Not available

Recruitment & Eligibility

Status
Authorised, recruiting
Sex
Not specified
Target Recruitment
142
Inclusion Criteria

Registration phase: Histologic or cytologic confirmation of NSCLC. If small-cell elements present, participant will be ineligible.

Registration phase: Patients of childbearing / reproductive potential should agree to use adequate birth control measures, as defined by the protocol, during the study treatment period and for: • At least 6 months after the last dose of pemetrexed-if pemetrexed was administered. • At least 6 months after the last dose of cemiplimab/placebo.

Registration phase: Women who are breast feeding should discontinue nursing prior to the first dose of study treatment and until: • At least 6 months after the last dose of pemetrexed, if pemetrexed was administered. • At least 6 months after the last dose of cemiplimab/placebo.

Registration phase: Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

At randomization: Stable disease, partial or complete response according to RECIST v.1.1 after 4 cycles of induction treatment and radical treatment of all residual disease (if applicable). Patients with progressive disease will be excluded.

At randomization: Anticipated life expectancy >12 weeks

At randomization: Hepatic function: • Serum total bilirubin ≤1.5x ULN (or ≤3x ULN, if liver metastases or in patients with history of Gilbert syndrome) • AST and/or ALT ≤3x ULN (or ≤5x ULN, if liver metastases)

At randomization: Renal function: GFR based on MDRD equation ≥30 mL/min

At randomization: Bone marrow function: • Haemoglobin ≥9.0 g/dL • ANC ≥1.5 x 10^9/L • Platelet count ≥100 x 10^9/L

At randomization: WOCBP must have a negative serum or highly negative urine pregnancy test within 7 days prior to the first dose of consolidation treatment.

Registration phase: Synchronous oligometastatic disease at diagnosis – and still oligometastatic at registration into the study - defined as maximum 5 metastases, in maximum 3 organs. Hilar, mediastinal and/or supraclavicular lymph nodes are not considered as metastases.

Registration phase: Measurable disease according to RECIST 1.1.

Registration phase: Age at registration ≥18 years

Registration phase: Eastern Cooperative Oncology Group performance status (ECOG PS)/ World Health Organization (WHO) 0-1.

Registration phase: Hepatic function: • Serum total bilirubin ≤1.5x upper limit of normal (ULN), or ≤3x ULN, if liver metastases or in patients with history of Gilbert syndrome • Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤3x ULN (or ≤5x ULN, if liver metastases)

Registration phase: Renal function: Glomerular filtration rate (GFR) based on the modification of diet in renal disease (MDRD) equation ≥30 mL/min

Registration phase: Bone marrow function: • Haemoglobin ≥9.0 g/dL • Absolute neutrophil count (ANC) ≥1.5 x 10^9/L • Platelet count ≥100 x 10^9/L

Registration phase: Women of childbearing potential (WOCBP) must have a negative serum or highly sensitive urine pregnancy test within 7 days prior to the first dose of treatment.

Exclusion Criteria

Registration phase: Presence of malignant pleural, pericardial and/or peritoneal effusion.

Registration phase: History of any solid or haematological malignancy in the past 3 years before registration. Exceptions include patients who underwent successful definitive treatment of basal or squamous cell carcinoma of the skin, or any in-situ carcinoma(s).

Registration phase: Any uncontrolled, intercurrent illness or clinical situation that would, in the judgment of investigator, limit compliance with study requirements.

Registration phase: Any uncontrolled active infection, defined as an infection ≥ grade 3 according to CTCAE version 5.0.

Registration phase: Any autoimmune disease that has required systemic treatment in the past 2 years (defined as any use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine for hypothyroidism or insulin for type I diabetes) is not considered a form of systemic treatment. The following treatments are allowed: • Intranasal, inhaled and topical steroids as well as local steroid injections (e.g., intra articular injection). • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent. • Systemic corticosteroid replacement therapy for adrenal or pituitary insufficiency. • Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)

Registration phase: Receipt of live vaccines (including attenuated) within 30 days of first study treatment.

Registration phase: Participation in any other clinical study involving an investigational drug or device within 4 weeks before registration.

Registration phase: History of documented allergic reaction or acute hypersensitivity reaction attributed to antibody treatments.

Registration phase: Sensitivity to any of the study interventions, or components thereof, or other allergy that, in the opinion of the investigator, contraindicates participation in the study.

Registration phase: Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol, understanding and completion of questionnaires and followup schedule; those conditions should be assessed and discussed with the patient before the enrolment in the trial

At randomization: Use of immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within 2 weeks prior to the first dose of cemiplimab/placebo. Patients who require brief courses of steroids (e.g., as prophylaxis for imaging studies due to hypersensitivity to contrast agents) can be included.

Registration phase: Known active hepatitis B or C, defined as a positive HBV surface antigen (HBsAg) result or positive HCV RNA.

Registration phase: Known active HIV infection, defined as >200 copies of HIV per ml of blood.

Registration phase: History of interstitial lung disease (e.g., idiopathic pulmonary fibrosis, organizing pneumonia) or history of non-infectious pneumonitis that required systemic glucocorticoids to assist with management. A history of radiation pneumonitis in the radiation field is permitted as long as pneumonitis resolved ≥12 months prior to registration.

Registration phase: Immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within 2 weeks prior to the first dose of cemiplimab. Patients who require brief courses of steroids (e.g., as prophylaxis for imaging studies due to hypersensitivity to contrast agents) can be included.

Registration phase: Presence of leptomeningeal carcinomatosis.

Registration phase: Tumour known to be positive for EGFR exon 19 or 21 mutations, ALK translocations or ROS1 fusions.

Registration phase: Prior pneumonectomy, radiotherapy (including mediastinal radiotherapy), chemotherapy, immune-check inhibitors or targeted therapy for lung cancer within the last 3 years before registration.

Registration phase: Previously treated brain metastases that are radiologically non-stable.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Primary Outcome Measures
NameTimeMethod
Progression Free Survival according to RECIST 1.1

Progression Free Survival according to RECIST 1.1

Secondary Outcome Measures
NameTimeMethod
Overall survival

Overall survival

Time to disease progression

Time to disease progression

Time to development of new metastatic lesions

Time to development of new metastatic lesions

Time to progression in oligometastatic lesions initially present at registration

Time to progression in oligometastatic lesions initially present at registration

AEs according to NCI-CTCAE v5.0 and SAEs

AEs according to NCI-CTCAE v5.0 and SAEs

Patient-reported symptoms and treatment side-effects as measured by the EORTC QLQ-C30 and IL316 questionnaires.

Patient-reported symptoms and treatment side-effects as measured by the EORTC QLQ-C30 and IL316 questionnaires.

Trial Locations

Locations (18)

Institut Paoli Calmettes

🇫🇷

Marseille, France

GIE Groupe hospitalier Paris Saint-Joseph/Vinci

🇫🇷

Paris Cedex 14, France

Centre Hospitalier De La Cote Basque

🇫🇷

Bayonne, France

Azienda Sanitaria Universitaria Friuli Centrale

🇮🇹

Udine, Italy

Humanitas Mirasole S.p.A.

🇮🇹

Rozzano, Italy

Azienda Unita Sanitaria Locale Della Romagna

🇮🇹

Ravenna, Italy

Fondazione IRCCS Policlinico San Matteo

🇮🇹

Pavia, Italy

Azienda Socio Sanitaria Territoriale Ovest Milanese

🇮🇹

Legnano, Italy

Ospedale Mater Salutis Di Legnago

🇮🇹

Legnago, Italy

Micancer Center S.L.P.

🇪🇸

Barcelona, Spain

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Institut Paoli Calmettes
🇫🇷Marseille, France
Philippe Rochigneux
Site contact
+33491223537
rochigneuxp@ipc.unicancer.fr
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