Clinical Trials /

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

NCT03977194

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief 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
  • 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 IDs

  • ORG STUDY ID: IFCT-1805
  • NCT ID: NCT03977194

Conditions

  • Non Small Cell Lung Cancer Metastatic

Interventions

DrugSynonymsArms
CarboplatinArm A : standard treatment
PaclitaxelArm A : standard treatment
AtezolizumabArm B : standard treatment + immunotherapy

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Arm A : standard treatmentActive ComparatorCarboplatine + paclitaxel (4 cycles of 28 days)
  • Carboplatin
  • Paclitaxel
Arm B : standard treatment + immunotherapyExperimentalCarboplatine + paclitaxel (4 cycles of 28 days) + atezolizumab (every 21 days) until progression or toxicity
  • Carboplatin
  • Paclitaxel
  • Atezolizumab

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

          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 (deletion LREA in exon 19, L858R ou L861X
             mutations in exon 21, G719A/S mutation in exon 18) or HER2 exon 20 insertion (either
             tissue or plasma cfDNA 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 or squamous 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 (e.g., bronchiolitis
             obliterans, COPD), 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.

         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
      
Maximum Eligible Age:89 Years
Minimum Eligible Age:70 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Survival
Time Frame:11 months after randomization of the last subject
Safety Issue:
Description:Time from randomization until death due to any cause

Secondary Outcome Measures

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

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Intergroupe Francophone de Cancerologie Thoracique

Trial Keywords

  • IFCT
  • ELDERLY
  • NSCLC

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