Phase III randomized trial of atezolizumab in elderly patients with advanced Non-Small-Cell Lung Cancer and receiving monthly carboplatin with weekly paclitaxel chemotherapy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Intergroupe Francophone De Cancerologie Thoracique

Participant type

Patients

Age range

65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

22 Jul 2019 → ongoing

Decision date (initial)

2024-12-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-515946-17-00

EudraCT number

2018-004805-18

ClinicalTrials.gov

NCT03977194

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

To determine the activity of anti-PDL1 antibody ATEZOLIZUMAB in elderly patient in first line treatment by measuring overall survival probability in patients treated in the standard arm versus overall survival probability in the experimental arm (atezolizumab + carboplatin and paclitaxel)

Secondary objectives 7

1. 1-year survival rate
2. Progression-Free Survival (PFS)
3. Best response rate
4. Duration of response
5. Quality of Life
6. Safety
7. Prognostic and predictive factors of survival (including some geriatric assessments)

Conditions and MedDRA coding

Non Small Cell Lung Cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. 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. 2. Histologically confirmed NSCLC. A cytologically-proven NSCLC is allowed if a cytoblock has been prepared.
3. 3. Age: 70 to 89 years
4. 4. Performance status ≤1.
5. 5. Stage IIIB or IIIC non irradiable or IV (8th classification TNM, UICC 2015)
6. 6. Measurable disease as defined by RECIST 1.1. The radiological assessment has to be done within the timelines indicated.
7. 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. 8. At least 3 weeks must have elapsed after major surgery or radiation therapy
9. 9. Adequate biological functions: Creatinine Clearance ≥ 45 mL/min (Cockroft 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 bilirubine ≤ 1,5 x ULN except for patients with proved, Gilbert syndrome (≤ 5 x ULN) or patients with hepatic metastases (≤ 3,0 mg/dL).
10. 10. Life expectancy of at least 12 weeks
11. 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. 12. Patient covered by a national health insurance
13. 13. Protected adults can participate if they are able to make decision about their medical treatment according to guardianship judgment.

Exclusion criteria 27

1. 1. Small cell lung cancer or tumors with mixt histology including a SCLC component
2. 2. Known EGFR activating tumor mutation
3. 3. Known ALK or ROS1 gene rearrangement as assessed by IH, FISH or NGS sequencing
4. 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. 5. Mini Mental Score < 24
6. 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. 7. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
8. 8. Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
9. 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. 10. Symptomatic brain metastases requiring corticosteroids.
11. 11. Spinal cord compression not definitely treated by surgery and/or radiation therapy or with neurological sequelae.
12. 12. Leptomeningeal disease
13. 13. Uncontrolled tumor-related pain.
14. 14. Uncontrolled or symptomatic or requiring Denosumab hypercalcemia.
15. 15. Corticosteroids > 10mg oral prednisone/day or equivalent.
16. 16. Immunosuppressive medications within 2 weeks before randomization
17. 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. 18. HIV positive serology (test at screening)
19. 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) or past or resolved hepatitis C virus (HCV) infection are eligible.
20. 20. Active tuberculosis
21. 21. Severe infection within 4 weeks before randomization
22. 22. Received therapeutic oral or iv antibiotics within 2 weeks before randomization.
23. 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. 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. 25. Polyneuropathy ≥ grade 2 CTC
26. 26. Treatment with an investigational drug during the 4 weeks preceding inclusion in the trial.
27. 27. Known allergy to Cremophor EL

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall survival

Secondary endpoints 3

1. Progression-free survival
2. Best overall response rate
3. Duration of response

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Intergroupe Francophone De Cancerologie Thoracique

Sponsor organisation

Intergroupe Francophone De Cancerologie Thoracique

Address

10 Rue De La Grange Bateliere

City

Paris

Postcode

75009

Country

France

Scientific contact point

Organisation

Intergroupe Francophone De Cancerologie Thoracique

Contact name

Contact

Public contact point

Organisation

Intergroupe Francophone De Cancerologie Thoracique

Contact name

Contact

Locations

1 EU/EEA country · 68 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications