Trial evaluating maintenance pembrolizumab (± pemetrexed) until progression versus observation (± pemetrexed) after 6 months of treatment by chemotherapy plus pembrolizumab in patients with advanced Lung Cancer
- Conditions
- Advanced Non Small Cell Lung CancerMedDRA version: 21.1Level: PTClassification code 10029522Term: Non-small cell lung cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2021-006044-27-FR
- Lead Sponsor
- IFCT
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 1360
1.Signed Written Informed Consent:
•Subjects must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal subject care.
•Subjects must be willing and able to comply with scheduled visits, treatment schedule, and laboratory testing.
2.Patients with histologically confirmed metastatic NSCLC (Stage IV accordingly to 8th classification TNM, UICC 2015). A cytologically-proven NSCLC is allowed if a cytoblock has been prepared.
3.PD-L1 tumor content as assessed locally by the investigator center.
4.Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
5.Weight loss< 10% within 3 months of study entry.
6.No prior systemic anticancer therapy (including EGFR or ALK inhibitors) given as primary therapy for advanced or metastatic disease.
7.Age= 18 years, <75 years
8.Life expectancy > 3 months
9.Measurable tumor disease by CT or MRI per RECIST 1.1 criteria
10.The Investigator must confirm prior to enrolment that the patient has adequate tumor tissue available. Tumor biopsy should be exploitable for molecular analysis.
Note: Tumor tissue collected after the patient was diagnosed with metastatic disease is preferred.
Tumor tissue sample must not be from locations previously radiated.
Tumor sample must be 1 block or at least 7 unstained slides of analyzable tissue.
If archival tissue is either insufficient or unavailable, the patient may still be eligible upon discussion with IFCT.
11.Adequate biological functions:
Creatinine Clearance = 45 mL/min (Cockroft or MDRD or CKD-epi); neutrophils= 1500/mm3 ; platelets =100 000/mm3 ; Hemoglobin= 9g/dL ; AST and ALT< 3x ULN, total bilirubin < 2xULN (patients with hepatic metastases or Gilbert’s syndrome must have AST and ALT = 5 x ULN and a baseline total bilirubin = 2xULN).
12.Women of childbearing potential (WOCBP) and sexually active should use an efficacious contraception method within the 28 days preceding the first dose and during the 6 months following the last dose of treatment. Women must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) prior to the start of study drug.
13.For Male subjects who are sexually active with WOCBP, an efficacious contraception method should be used during the treatment and during the 6 months following the last dose.
14.Patient has national health insurance coverage.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1224
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 136
1.Small cell lung cancer or tumors with mixed histology including a SCLC component.
2.Known EGFR activating tumor mutation (deletion LREA in exon 19, L858R ou L861X mutations in exon 21, G719A/S mutation in exon 18, exon 20 insertion) or HER2 exon 20 insertion (either tissue or plasma cfDNA mutation).
3.Known ALK, ROS1, Ret, NTRK, NRG1 gene rearrangement as assessed by immunohistochemistry, FISH or NGS (ADN or ARN) sequencing by local genetics and/or pathology laboratory.
4.Previous or active cancer within the previous 3 years (except for treated carcinoma in situ of the cervix, or basal cell skin cancer treated or not). Patients with a prostate adenocarcinoma history within the previous 3 years could be included in case of localized prostate cancer, with good prognostic factors according to d'Amico classification (=T2a, score de Gleason = 6 and PSA = 10 (ng/ml)) provided they were treated in a curative way (surgery or radiotherapy, without any chemotherapy).
5.Superior vena cava syndrome persisting despite VCS stenting.
6.Radiotherapy needed at initiation of tumour treatment, except bone palliative radiotherapy on a painful or compressive metastasis, respecting 1 week delay between the end of radiotherapy and the beginning of treatment
7.Symptomatic untreated brain metastasis (without previous whole brain radiotherapy or stereotactic ablative brain radiotherapy or without surgical resection). At least 2 weeks delay between the end of radiotherapy and the beginning of induction immunotherapy treatment should be respected. Asymptomatic brain metastasis, not needing corticosteroids greater than 10 mg prednisone equivalent daily or mannitol infusions, are allowed.
8.History of previous primary immunodeficiency, organ transplantation needing an immunosuppressive treatment, any immunosuppressive drug within 28 days before randomization date, or history of severe toxicity (grade 3/4) by immune mechanism linked to another immunotherapy treatment.
9.Systemic treatment with corticosteroids with greater dose than 10 mg prednisone equivalent daily, within 14 days before initiation of the immunotherapy induction. Inhaled, nasal or topic corticosteroids are allowed.
10.History of active autoimmune disease including but not limited to rheumatoid polyarthritis, myasthenia, autoimmune hepatitis, systemic Lupus, Wegener's granulomatosis, vascular thrombosis associated with antiphospholipid syndrome, Sjogren’s syndrome with interstitial pulmonary disease, recent Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
Patients with type I diabetes, or hypothyroidy, or immune cutaneous disease (vitiligo, psoriasis, alopecia) or benign rheumatoid polyarthritis not needing any immunosuppressive systemic treatment, or benign sicca syndrome (Sjogren) without interstitial pulmonary disease, or history of past Guillain-Barre syndrome, totally reversible with no sequalae, no systemic immunosuppressive treatment during the last 20 years, are allowed to be included.
11.Active inflammatory intestinal disease (diverticulosis, Crohn disease, Hemorrhagic recto-colitis, coeliac disease) or any serious chronic intestinal disease with uncontrolled diarrhea.
12.Active uncontrolled infection including tuberculosis, known acute viral hepatitis B and C according to serological tests. Patients with serological sequalae of cured viral hepatitis are allowed to be included. Past primary pulmonary tuberculosis in youth does not consist of
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method