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

Phase 3

Active, not recruiting

• Conditions: Non Small Cell Lung Cancer Metastatic
• Interventions: Drug: Carboplatin; Drug: Paclitaxel; Drug: Atezolizumab

• Registration Number: NCT03977194
• Lead Sponsor: Intergroupe Francophone de Cancerologie Thoracique

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-06-05
• Study First Submitted QC: 2019-06-05
• Study First Posted: 2019-06-06
• Study Start: 2019-07-23
• Primary Completion: 2024-08-31
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-26
• Last Update Posted: 2025-04-01
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 500

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A : standard treatment	Carboplatin	Carboplatine + paclitaxel (4 cycles of 28 days)
Arm A : standard treatment	Paclitaxel	Carboplatine + paclitaxel (4 cycles of 28 days)
Arm B : standard treatment + immunotherapy	Carboplatin	Carboplatine + paclitaxel (4 cycles of 28 days) + atezolizumab (every 21 days) until progression or toxicity
Arm B : standard treatment + immunotherapy	Paclitaxel	Carboplatine + paclitaxel (4 cycles of 28 days) + atezolizumab (every 21 days) until progression or toxicity
Arm B : standard treatment + immunotherapy	Atezolizumab	Carboplatine + paclitaxel (4 cycles of 28 days) + atezolizumab (every 21 days) until progression or toxicity

Primary Outcome Measures

Name	Time	Method
Overall Survival	11 months after randomization of the last subject	Time from randomization until death due to any cause

Secondary Outcome Measures

Name	Time	Method
Progression-free survival	11 months after randomization of the last subject	Time from randomization to first observation of progression (according to RECIST v1.1) or date of death (from any cause).
Best overall response rate	11 months after randomization of the last subject	Best response according to RECIST v1.1 from start to end of study treatment
Duration of response	11 months after randomization of the last subject	Time from documentation of tumor response to disease progression

Trial Locations

Locations (68)

Bayonne - CH; 🇫🇷 Bayonne, France

Avignon - Institut Sainte-Catherine; 🇫🇷 Avignon, France

Metz - Thionville CHR; 🇫🇷 Ars-Laquenexy, France

Besançon - CHU; 🇫🇷 Besançon, France

Auxerre - CH; 🇫🇷 Auxerre, France

Carcassone - CH; 🇫🇷 Carcassonne, France

Paris - Curie; 🇫🇷 Paris, France

Bobigny - APHP - Hôpital Avicenne; 🇫🇷 Bobigny, France

Avignon - CH; 🇫🇷 Avignon, France

Pau - CHG; 🇫🇷 Pau, France

Chauny - Centre Hospitalier; 🇫🇷 Chauny, France

Paris - Hôpital Cochin; 🇫🇷 Paris, France

Caen - CHU Côte de Nacre; 🇫🇷 Caen, France

Clermont Ferrand - CHU; 🇫🇷 Clermont Ferrand, France

Clamart - Hôpital Percy; 🇫🇷 Clamart, France

Suresnes - Hopital Foch; 🇫🇷 Suresnes, France

Toulon - CHI; 🇫🇷 Toulon, France

Toulon - HIA; 🇫🇷 Toulon, France

Bordeaux - Polyclinique Nord; 🇫🇷 Bordeaux, France

Lyon - URCOT; 🇫🇷 Pierre-Bénite, France

Valence - CH; 🇫🇷 Valence, France

Paris - Hôpital Saint Joseph; 🇫🇷 Paris, France

Sens - CH; 🇫🇷 Sens, France

Cannes - CH; 🇫🇷 Cannes, France

Centre Hospitalier Mémorial de Saint-Lô; 🇫🇷 Saint-Lô, France

Boulogne - Ambroise Paré; 🇫🇷 Boulogne-Billancourt, France

Saint- Mandé - HIA Begin; 🇫🇷 Saint-Mandé, France

La Réunion - CHU (Site Sud); 🇫🇷 Saint-Pierre, France

Villefranche-Sur-Saône - Hôpital Nord-Ouest; 🇫🇷 Villefranche-Sur-Saône, France

Le Mans - CHG; 🇫🇷 Le Mans, France

Orléans - CH; 🇫🇷 Orléans, France

Lille - GHICL; 🇫🇷 Lille, France

Limoges - CHU; 🇫🇷 Limoges, France

Rodez - CH; 🇫🇷 Rodez, France

Valenciennes - Clinique; 🇫🇷 Valenciennes, France

Toulouse - CHU; 🇫🇷 Toulouse, France

Saint-Etienne - CHU; 🇫🇷 Saint-Étienne, France

Nice - CRLCC; 🇫🇷 Nice, France

Saint-Priest - Institut de Cancérologie de la Loire; 🇫🇷 Saint-priest En Jarez, France

Quint-Fonsegrives - Clinique de la Croix du Sud; 🇫🇷 Quint-Fonsegrives, France

Saint-Cloud - Centre René Huguenin; 🇫🇷 Saint-Cloud, France

Paris - APHP - Hopital Tenon; 🇫🇷 Paris, France

Paris - APHP Bichat; 🇫🇷 Paris, France

Tours - CHU; 🇫🇷 Tours, France

La Réunion - CHU (site Félix GUYON); 🇫🇷 Saint-Denis, France

Abbeville - CH; 🇫🇷 Abbeville, France

Aix-en-Provence - CH; 🇫🇷 Aix-en-Provence, France

Annemasse - CH; 🇫🇷 Ambilly, France

Bordeaux - CHU Hôpital Haut-Lévèque; 🇫🇷 Bordeaux, France

Centre Hospitalier de Chambéry; 🇫🇷 Chambéry, France

Cholet - CH; 🇫🇷 Cholet, France

Colmar - CH; 🇫🇷 Colmar, France

Cornebarrieu - Clinique des Cèdres; 🇫🇷 Cornebarrieu, France

Dijon - Centre Georges-François Leclerc; 🇫🇷 Dijon, France

Grenoble - CHU; 🇫🇷 Grenoble, France

Lille - Polyclinique de la Louvière; 🇫🇷 Lille, France

Marseille - AP-HM Hôpital Nord; 🇫🇷 Marseille, France

Marseille - Hôpital Européen; 🇫🇷 Marseille, France

Lyon - Hôpital Jean Mermoz; 🇫🇷 Lyon, France

Lorient - CHBS; 🇫🇷 Lorient, France

Marseille - Institut Paoli Calmette; 🇫🇷 Marseille, France

Meaux - CH; 🇫🇷 Meaux, France

Mulhouse - GHRMSA; 🇫🇷 Mulhouse, France

Montauban - CH; 🇫🇷 Montauban, France

Centre Hospitalier des Pays de Morlaix; 🇫🇷 Morlaix, France

Nantes - CHU Hôpital Laënnec; 🇫🇷 Nantes, France

Nancy - Institut de Cancérologie de Lorraine; 🇫🇷 Nancy, France

Strasbourg - Nouvel Hôpital Civil; 🇫🇷 Strasbourg, France