Atezolizumab in Elderly Patients With Advanced Non-Small-Cell Lung Cancer and Receiving Carboplatin Paclitaxel Chemotherapy

Non Small Cell Lung Cancer Metastatic Clinical Trial

— ELDERLY  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03977194
• Other study ID #: IFCT-1805
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: July 23, 2019
• Est. completion date: December 2026

Study information

• Verified date: December 2023
• Source: Intergroupe Francophone de Cancerologie Thoracique
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 500
• Est. completion date: December 2026
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 70 Years to 89 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non Small Cell Lung Cancer Metastatic

Intervention

Drug:
• Carboplatin
AUC 6 every 4 weeks
• Paclitaxel
90 mg/m² D1, 8, 15, every 4 weeks
• Atezolizumab
1200 mg every 3 weeks

Locations

Country	Name	City	State
France	Abbeville - CH	Abbeville
France	Aix-en-Provence - CH	Aix-en-Provence
France	Annemasse - CH	Ambilly
France	Metz - Thionville CHR	Ars-Laquenexy
France	Auxerre - CH	Auxerre
France	Avignon - CH	Avignon
France	Avignon - Institut Sainte-Catherine	Avignon
France	Bayonne - CH	Bayonne
France	Besançon - CHU	Besançon
France	Bobigny - APHP - Hôpital Avicenne	Bobigny
France	Bordeaux - CHU Hôpital Haut-Lévèque	Bordeaux
France	Bordeaux - Polyclinique Nord	Bordeaux
France	Boulogne - Ambroise Paré	Boulogne-Billancourt
France	Caen - CHU Côte de Nacre	Caen
France	Cannes - CH	Cannes
France	Carcassone - CH	Carcassonne
France	Centre Hospitalier de Chambéry	Chambéry
France	Chauny - Centre Hospitalier	Chauny
France	Cholet - CH	Cholet
France	Clamart - Hôpital Percy	Clamart
France	Clermont Ferrand - CHU	Clermont Ferrand
France	Colmar - CH	Colmar
France	Cornebarrieu - Clinique des Cèdres	Cornebarrieu
France	Dijon - Centre Georges-François Leclerc	Dijon
France	Grenoble - CHU	Grenoble
France	Le Mans - CHG	Le Mans
France	Lille - GHICL	Lille
France	Lille - Polyclinique de la Louvière	Lille
France	Limoges - CHU	Limoges
France	Lorient - CHBS	Lorient
France	Lyon - Hôpital Jean Mermoz	Lyon
France	Marseille - AP-HM Hôpital Nord	Marseille
France	Marseille - Hôpital Européen	Marseille
France	Marseille - Institut Paoli Calmette	Marseille
France	Meaux - CH	Meaux
France	Montauban - CH	Montauban
France	Centre Hospitalier des Pays de Morlaix	Morlaix
France	Mulhouse - GHRMSA	Mulhouse
France	Nancy - Institut de Cancérologie de Lorraine	Nancy
France	Nantes - CHU Hôpital Laënnec	Nantes
France	Nice - CRLCC	Nice
France	Orléans - CH	Orléans
France	Paris - APHP - Hopital Tenon	Paris
France	Paris - APHP Bichat	Paris
France	Paris - Curie	Paris
France	Paris - Hôpital Cochin	Paris
France	Paris - Hôpital Saint Joseph	Paris
France	Pau - CHG	Pau
France	Lyon - URCOT	Pierre-Bénite
France	Quint-Fonsegrives - Clinique de la Croix du Sud	Quint-Fonsegrives
France	Rodez - CH	Rodez
France	Saint-Cloud - Centre René Huguenin	Saint-Cloud
France	La Réunion - CHU (site Félix GUYON)	Saint-Denis
France	Saint-Etienne - CHU	Saint-Étienne
France	Centre Hospitalier Mémorial de Saint-Lô	Saint-Lô
France	Saint- Mandé - HIA Begin	Saint-Mandé
France	La Réunion - CHU (Site Sud)	Saint-Pierre
France	Saint-Priest - Institut de Cancérologie de la Loire	Saint-priest En Jarez
France	Sens - CH	Sens
France	Strasbourg - Nouvel Hôpital Civil	Strasbourg
France	Suresnes - Hopital Foch	Suresnes
France	Toulon - CHI	Toulon
France	Toulon - HIA	Toulon
France	Toulouse - CHU	Toulouse
France	Tours - CHU	Tours
France	Valence - CH	Valence
France	Valenciennes - Clinique	Valenciennes
France	Villefranche-Sur-Saône - Hôpital Nord-Ouest	Villefranche-Sur-Saône

Sponsors (1)

Lead Sponsor	Collaborator
Intergroupe Francophone de Cancerologie Thoracique

Country where clinical trial is conducted

France, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival	Time from randomization until death due to any cause	11 months after randomization of the last subject
Secondary	Progression-free survival	Time from randomization to first observation of progression (according to RECIST v1.1) or date of death (from any cause).	11 months after randomization of the last subject
Secondary	Best overall response rate	Best response according to RECIST v1.1 from start to end of study treatment	11 months after randomization of the last subject
Secondary	Duration of response	Time from documentation of tumor response to disease progression	11 months after randomization of the last subject

External Links

•   IFCT website