Double Immune Checkpoint Inhibitors in PD-L1-positive Stage IV Non-small Lung CancEr

  • STATUS
    Recruiting
  • End date
    May 25, 2023
  • participants needed
    1360
  • sponsor
    Intergroupe Francophone de Cancerologie Thoracique
Updated on 25 January 2021
Investigator
Nicolas CLOAREC, Dr
Primary Contact
Caen - CHU C te de Nacre (0.8 mi away) Contact
+45 other location
cancer
gilbert's syndrome
metastasis
liver metastasis
tumor cells
pd-l1
nivolumab
ipilimumab

Summary

Non Small Cell lung cancer (NSCLC) remains the first cause of death by cancer in the World. For the patients presenting a NSCLC stage IV, the median of survival is about 15 months today. The chemotherapy with platinum is the standard treatment for these patients but immunotherapy showed these efficacy in 1st line for patients PD-L1 positive. On the other hand, the duration of treatment by immunotherapy is not clear. Indeed, prolonged responses and long survivals have been described in patients having interrupted the treatment. In the melanoma, a treatment of 6 months of ipilimumab demonstrated its efficacy. The objective of the study is to demonstrate that a treatment of 6 months followed by an observation (stop and go) is not less effective than a treatment given until progression or toxicity. This strategy would allow to decrease the accumulated toxicities, to improve the quality of life of the patients and to decrease the costs.

Details
Condition Non Small Cell Lung Cancer Metastatic
Treatment Ipilimumab, Nivolumab
Clinical Study IdentifierNCT03469960
SponsorIntergroupe Francophone de Cancerologie Thoracique
Last Modified on25 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

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
\. Histologically-proven NSCLC (squamous or non-squamous)
\. Stage IV (M1, including M1a pleural involvement) disease (8th
classification TNM, UICC 2015)
\. ECOG PS < 1
\. Weight loss< 10% in previous 3 months
\. No prior systemic anticancer therapy (including EGFR or ALK inhibitors)
given as primary therapy for advanced or metastatic disease
\. Age 18 years, <75 years
\. Life expectancy > 3 months
\. Measurable tumor disease by CT or MRI per RECIST 1.1 criteria
\. Available tumor samples for centralized PD-L1 immunohistochemistry
analysis
\. PD-L1 tumor content 1% and < 50% tumor cells as assessed locally by the
investigator center
\. Adequate biological functions
Creatinine Clearance 50 mL/min (Cockcroft or MDRD or CKD-epi); neutrophiles
mm3 ; platelets 100 000/mm3 ; Hemoglobin 9g/dL ; hepatic enzymes < 3x
ULN, total bilirubin 1,5 x ULN except for patients with proved, Gilbert
syndrome ( 5 x ULN) or patients with hepatic metastases ( 3,0 mg/dL)
\. 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) within 24 hours prior to the start of study drug
For Male subjects who are sexually active with WOCBP, an efficacious
contraception method should be used during the treatment and during the 7
months following the last dose
Investigators shall counsel WOCBP and male subjects who are sexually active
with WOCBP on the importance of pregnancy prevention and the implications of
an unexpected pregnancy. Investigators shall advise WOCBP and male subjects
who are sexually active with WOCBP on the use of highly effective methods of
contraception. Highly effective methods of contraception have a failure rate
of < 1% when used consistently and correctly. At a minimum, subjects must
agree to the use of two methods of contraception, with one method being highly
effective and the other method being either highly effective or less
effective
\. Patient inclusion validated by a multidisciplinary meeting

Exclusion Criteria

Small cell lung cancer or tumors with mixt histology including a SCLC component
Known EGFR activating tumor mutation (deletion LREA in exon 19, L858R ou L861X mutations in exon 21, G719A/S mutation in exon 18) or HER exon 20 insertion (either tissue or plasma cfDNA mutation)
Known ALK or ROS1 gene rearrangement as assessed by immunohistochemistry, FISH or NGS sequencing
Previous or active cancer within the previous 5 years (except for treated carcinoma in situ of the cervix or basal cell skin cancer). Patients with a prostate adenocarcinoma history within the previous 5 years could be included in case of localized prostate cancer, with good prognostic factors according to d'Amico classification ( T2a and Score de Gleason 6 and PSA (ng/ml) 10), provided they were treated in a curative way (surgery or radiotherapy, without any chemotherapy)
Superior vena cava (SVC) syndrome persisting after SVC stenting
Thoracic radiotherapy needed at initiation of tumor treatment, except bone palliative radiotherapy on a painful or compressive metastasis, respecting 4 weeks delay between the end of radiotherapy and the beginning of induction immunotherapy treatment
Symptomatic untreated brain metastasis (without previous whole brain radiotherapy or stereotactic ablative brain radiotherapy or without surgical resection). At least 4 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, with no evolution on brain MRI or CT-scan within the previous month are allowed
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
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
History of active autoimmune disease including rheumatoid polyarthritis, Lupus, Wegener disease. Patients with type I diabetes, or hypothyroidism, or immune cutaneous disease (vitiligo, psoriasis, alopecia) not needing any immunosuppressive systemic treatment, are allowed to be included
Active inflammatory intestinal disease (diverticulosis, Crohn disease, Hemorrhagic recto-colitis, coeliac disease) or any serious chronic intestinal disease with uncontrolled diarrhea
Active uncontrolled infection including tuberculosis, known acute viral hepatitis B and C according to serological tests. Patients with serological sequelae of cured viral hepatitis are allowed to be included
HIV known infection
Living attenuated vaccine received within the 30 previous days
Previous treatment with anti-PD-1, anti-PD-L1 or Anti-CTLA4 antibody
Previous treatment with chemotherapy
General serious condition such as congestive uncontrolled cardiac failure, uncontrolled cardiac arrythmia, uncontrolled ischemic cardiac disease (unstable angina or history of myocardial infarction in the previous 6 months), history or stroke within the 6 previous months
Pre-existing lung interstitial disease as assessed by the diagnosis CT-scan
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