Clinical trial NCT03977194: Atezolizumab in Elderly Patients With Advanced Non-Small-Cell Lung Cancer and Receiving Carboplatin Paclitaxel Chemotherapy
Official title: Phase III Randomized Trial of Atezolizumab in Elderly Patients With Advanced Non-Small-Cell Lung Cancer and Receiving Monthly Carboplatin With Weekly Paclitaxel Chemotherapy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Non Small Cell Lung Cancer Metastatic
Keywords: IFCT
ELDERLY
NSCLC
immunotherapy
chemotherapy
Lead sponsor: Intergroupe Francophone de Cancerologie Thoracique
Sponsor class: OTHER
First posted: 2019-06-06
Enrollment: 500
Sex: ALL
Minimum age (years): 70
Maximum age (years): 89
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Non Small Cell Lung Cancer (NSCLC) remains the leading cause of death by cancer in the world. Because of the increase in lung cancer incidence with age and the increase of life expectancy, about half of the patients are patients aged 70 or older. Several clinical trials have shown the interest of adding immunotherapy to standard 1st line chemotherapy in NSCLC. Although in these studies there was not necessarily a higher age limit, in fact the proportion of included patients aged 75 or older remains low (between 7 and 10%). It is therefore necessary to conduct a trial dedicated to these patients in order to determine whether immunotherapy is as effective and tolerated as in the general population.


Eligibility criteria: Inclusion Criteria:

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. Histologically confirmed NSCLC. A cytologically-proven NSCLC is allowed if a cytoblock has been prepared.
3. Age: 70 to 89 years
4. Performance status ≤1.
5. Stage IIIB or IIIC non irradiable or IV (8th classification TNM, UICC 2015)
6. Measurable disease as defined by RECIST 1.1. The radiological assessment has to be done within the timelines indicated.
7. No prior systemic anticancer therapy (including EGFR or ALK inhibitors) given as primary therapy for advanced or metastatic disease. Previously irradiated lesion must not be the only measurable site of disease.
8. At least 3 weeks must have elapsed after major surgery or radiation therapy
9. Adequate biological functions:

   Creatinine Clearance ≥ 45 mL/min (Cockcroft or MDRD or CKD-epi); neutrophiles ≥ 1500/mm3 ; platelets ≥100 000/mm3 ; Hemoglobin ≥ 9g/dL ; hepatic enzymes \< 3x ULN except for patients with hepatic metastases (\< 5 x 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).
10. Life expectancy of at least 12 weeks
11. For male patients with female partners of childbearing potential, agreement (by patient and/or partner) to use a highly effective form(s) of contraception that results in a low failure rate \[\< 1% per year\] when used consistently and correctly, and to continue its use for 6 months after the last dose of treatment. Male patients should not donate sperm during this study and for at least 6 months after the last dose of treatment.

    Oral contraception should always be combined with an additional contraceptive method because of a potential interaction with the treatment. Male patients must always use a condom.
12. Patient covered by a national health insurance
13. Protected adults can participate if they are able to make decision about their medical treatment according to guardianship judgment.

Exclusion Criteria:

1. Small cell lung cancer or tumors with mixt histology including a SCLC component
2. Known EGFR activating tumor mutation.
3. Known ALK or ROS1 gene rearrangement as assessed by IH, FISH or NGS sequencing
4. Previous or active cancer within the previous 3 years with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal cell skin cancer or ductal carcinoma in situ treated surgically with curative intent. For other type of cancer, please contact IFCT). 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 and Score de Gleason ≤ 6 and PSA (ng/ml) ≤ 10), provided they were treated in a curative way (surgery or radiotherapy ± hormonotherapy, without any chemotherapy)
5. Mini Mental Score \< 24
6. Previous systemic treatment (including but not limited to chemotherapy, targeted treatment or immunotherapy) except for adjuvant therapy given more than 5 years ago.
7. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
8. Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
9. History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone are eligible for this study.

   Patients with rheumatoid arthritis without exacerbation during one year and with no more than 10 mg oral prednisone /day or equivalent may be included after rheumatologist advice.

   Patients with controlled Type 1 diabetes mellitus on a stable dose of insulin regimen are eligible for this study

   Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
   * Rash must cover less than 10% of body surface area (BSA).
   * Disease is well controlled at baseline and only requiring low potency topical steroids.
   * No acute exacerbations of underlying condition within the previous 12 months (not requiring PUVA \[psoralen plus ultraviolet A radiation\], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, high potency or oral steroids)
10. Symptomatic brain metastases requiring corticosteroids.
11. Spinal cord compression not definitely treated by surgery and/or radiation therapy or with neurological sequelae.
12. Leptomeningeal disease
13. Uncontrolled tumor-related pain.
14. Uncontrolled or symptomatic or requiring Denosumab hypercalcemia .
15. Corticosteroids \> 10mg oral prednisone/day or equivalent.
16. Immunosuppressive medications within 2 weeks before randomization
17. History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
18. HIV positive serology (test at screening),
19. Patients with active hepatitis B (chronic or acute; defined as having a positive hepatitis B surface antigen HBsAg test at screening) or hepatitis C Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as the presence of hepatitis B core antibody \[HBcAb\] and absence of HBsAg) are eligible only if they are negative for HBV DNA.

    Patients positive for hepatitis C virus (HCV) antibody are eligible only if PCR is negative for HCV RNA.
20. Active tuberculosis
21. Severe infection within 4 weeks before randomization
22. Received therapeutic oral or iv antibiotics within 2 weeks before randomization.
23. Administration of live attenuated vaccine within four weeks before randomization or anticipation that such a live attenuated vaccine will be required during the study.
24. Serious undergoing diseases or comorbidities precluding the possibility for the patient to receive the treatments, including but not limited to unstable angina or uncontrolled cardiac disease.
25. Polyneuropathy ≥ grade 2 CTC
26. Treatment with an investigational drug during the 4 weeks preceding inclusion in the trial.
27. Known allergy to Cremophor EL

Primary outcomes:
measure: Overall Survival
timeFrame: 11 months after randomization of the last subject
Secondary outcomes:
measure: Progression-free survival
timeFrame: 11 months after randomization of the last subject
measure: Best overall response rate
timeFrame: 11 months after randomization of the last subject
measure: Duration of response
timeFrame: 11 months after randomization of the last subject
Other outcomes:
Locations:
city: Abbeville
country: France
facility: Abbeville - CH
city: Aix-en-Provence
country: France
facility: Aix-en-Provence - CH
city: Ambilly
country: France
facility: Annemasse - CH
city: Ars-Laquenexy
country: France
facility: Metz - Thionville CHR
city: Auxerre
country: France
facility: Auxerre - CH
city: Avignon
country: France
facility: Avignon - Institut Sainte-Catherine
city: Avignon
country: France
facility: Avignon - CH
city: Bayonne
country: France
facility: Bayonne - CH
city: Besançon
country: France
facility: Besançon - CHU
city: Bobigny
country: France
facility: Bobigny - APHP - Hôpital Avicenne
city: Bordeaux
country: France
facility: Bordeaux - CHU Hôpital Haut-Lévèque
city: Bordeaux
country: France
facility: Bordeaux - Polyclinique Nord
city: Boulogne-Billancourt
country: France
facility: Boulogne - Ambroise Paré
city: Caen
country: France
facility: Caen - CHU Côte de Nacre
city: Cannes
country: France
facility: Cannes - CH
city: Carcassonne
country: France
facility: Carcassone - CH
city: Chambéry
country: France
facility: Centre Hospitalier de Chambéry
city: Chauny
country: France
facility: Chauny - Centre Hospitalier
city: Cholet
country: France
facility: Cholet - CH
city: Clamart
country: France
facility: Clamart - Hôpital Percy
city: Clermont Ferrand
country: France
facility: Clermont Ferrand - CHU
city: Colmar
country: France
facility: Colmar - CH
city: Cornebarrieu
country: France
facility: Cornebarrieu - Clinique des Cèdres
city: Dijon
country: France
facility: Dijon - Centre Georges-François Leclerc
city: Grenoble
country: France
facility: Grenoble - CHU
city: Le Mans
country: France
facility: Le Mans - CHG
city: Lille
country: France
facility: Lille - GHICL
city: Lille
country: France
facility: Lille - Polyclinique de la Louvière
city: Limoges
country: France
facility: Limoges - CHU
city: Lorient
country: France
facility: Lorient - CHBS
city: Lyon
country: France
facility: Lyon - Hôpital Jean Mermoz
city: Marseille
country: France
facility: Marseille - AP-HM Hôpital Nord
city: Marseille
country: France
facility: Marseille - Hôpital Européen
city: Marseille
country: France
facility: Marseille - Institut Paoli Calmette
city: Meaux
country: France
facility: Meaux - CH
city: Montauban
country: France
facility: Montauban - CH
city: Morlaix
country: France
facility: Centre Hospitalier des Pays de Morlaix
city: Mulhouse
country: France
facility: Mulhouse - GHRMSA
city: Nancy
country: France
facility: Nancy - Institut de Cancérologie de Lorraine
city: Nantes
country: France
facility: Nantes - CHU Hôpital Laënnec
city: Nice
country: France
facility: Nice - CRLCC
city: Orléans
country: France
facility: Orléans - CH
city: Paris
country: France
facility: Paris - Hôpital Saint Joseph
city: Paris
country: France
facility: Paris - APHP - Hopital Tenon
city: Paris
country: France
facility: Paris - APHP Bichat
city: Paris
country: France
facility: Paris - Curie
city: Paris
country: France
facility: Paris - Hôpital Cochin
city: Pau
country: France
facility: Pau - CHG
city: Pierre-Bénite
country: France
facility: Lyon - URCOT
city: Quint-Fonsegrives
country: France
facility: Quint-Fonsegrives - Clinique de la Croix du Sud
city: Rodez
country: France
facility: Rodez - CH
city: Saint-Cloud
country: France
facility: Saint-Cloud - Centre René Huguenin
city: Saint-Denis
country: France
facility: La Réunion - CHU (site Félix GUYON)
city: Saint-Lô
country: France
facility: Centre Hospitalier Mémorial de Saint-Lô
city: Saint-Mandé
country: France
facility: Saint- Mandé - HIA Begin
city: Saint-Pierre
country: France
facility: La Réunion - CHU (Site Sud)
city: Saint-priest En Jarez
country: France
facility: Saint-Priest - Institut de Cancérologie de la Loire
city: Saint-Étienne
country: France
facility: Saint-Etienne - CHU
city: Sens
country: France
facility: Sens - CH
city: Strasbourg
country: France
facility: Strasbourg - Nouvel Hôpital Civil
city: Suresnes
country: France
facility: Suresnes - Hopital Foch
city: Toulon
country: France
facility: Toulon - CHI
city: Toulon
country: France
facility: Toulon - HIA
city: Toulouse
country: France
facility: Toulouse - CHU
city: Tours
country: France
facility: Tours - CHU
city: Valence
country: France
facility: Valence - CH
city: Valenciennes
country: France
facility: Valenciennes - Clinique
city: Villefranche-Sur-Saône
country: France
facility: Villefranche-Sur-Saône - Hôpital Nord-Ouest
Study officials:
affiliation: Strasbourg - NHC
name: Elisabeth QUOIX
role: STUDY_CHAIR
affiliation: Strasbourg - NHC
name: Céline MASCAUX
role: STUDY_CHAIR
References:
citation: Quoix E, Zalcman G, Oster JP, Westeel V, Pichon E, Lavole A, Dauba J, Debieuvre D, Souquet PJ, Bigay-Game L, Dansin E, Poudenx M, Molinier O, Vaylet F, Moro-Sibilot D, Herman D, Bennouna J, Tredaniel J, Ducolone A, Lebitasy MP, Baudrin L, Laporte S, Milleron B; Intergroupe Francophone de Cancerologie Thoracique. Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised, phase 3 trial. Lancet. 2011 Sep 17;378(9796):1079-88. doi: 10.1016/S0140-6736(11)60780-0. Epub 2011 Aug 8.