Clinical Trials /

Immunotherapy in Patient With Poor General Condition

NCT04108026

Description:

Immunotherapeutic approaches targeting immune checkpoint proteins PD-1/PD-L1 have recently demonstrated clinical efficacy in several cancer types, and have changed the therapeutic landscape in metastatic melanoma or non-small cell lung cancer (NSCLC). The monoclonal anti-PD-1 antibody nivolumab has been registered by both FDA (Food and Drug Administration) and EMA (European Medicine Agency), for metastatic NSCLC patients, after failure of a prior platinum-based chemotherapy. The approval was based on the results of phase III clinical trials in metastatic NSCLC. But all the trials only enrolled patients with good general condition, PS (Performance Status) 0 or 1. However, the prevalence of poor PS patients at time of diagnosis is high in lung cancer patients. For patients with metastatic NSCLC and PS 3, there is no standard treatment except best supportive care, since all trials that accrued unselected PS 3 patients fail to prove any survival advantage, and most PS >3 patients die within 2 to 4 months from diagnosis. Indeed, these patients are currently excluded from clinical trials. Specific dedicated clinical trials and treatment guidelines for this patient population are urgently needed, taking into account for the high prevalence of such patients.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Immunotherapy in Patient With Poor General Condition
  • Official Title: A Phase II Single-arm Trial Evaluating Safety and Efficacy of Durvalumab in ECOG Performance Status 2-3, Treatment-naive, Patients With Stage IV Non-Small Cell Lung Cancer (NSCLC) and High PD-L1 Tumor Expression

Clinical Trial IDs

  • ORG STUDY ID: IFCT-1802
  • NCT ID: NCT04108026

Conditions

  • Non-small Cell Lung Cancer Stage IV

Interventions

DrugSynonymsArms
DurvalumabImmunotherapy

Purpose

Immunotherapeutic approaches targeting immune checkpoint proteins PD-1/PD-L1 have recently demonstrated clinical efficacy in several cancer types, and have changed the therapeutic landscape in metastatic melanoma or non-small cell lung cancer (NSCLC). The monoclonal anti-PD-1 antibody nivolumab has been registered by both FDA (Food and Drug Administration) and EMA (European Medicine Agency), for metastatic NSCLC patients, after failure of a prior platinum-based chemotherapy. The approval was based on the results of phase III clinical trials in metastatic NSCLC. But all the trials only enrolled patients with good general condition, PS (Performance Status) 0 or 1. However, the prevalence of poor PS patients at time of diagnosis is high in lung cancer patients. For patients with metastatic NSCLC and PS 3, there is no standard treatment except best supportive care, since all trials that accrued unselected PS 3 patients fail to prove any survival advantage, and most PS >3 patients die within 2 to 4 months from diagnosis. Indeed, these patients are currently excluded from clinical trials. Specific dedicated clinical trials and treatment guidelines for this patient population are urgently needed, taking into account for the high prevalence of such patients.

Trial Arms

NameTypeDescriptionInterventions
ImmunotherapyExperimentalDurvalumab 1500 mg every 4 weeks until the progression of disease, discontinuation due to toxicity or withdrawal of consent, for a maximum duration of 2 years.
  • Durvalumab

Eligibility Criteria

        Inclusion Criteria:

          1. Subjects must have signed and dated an IEC (Independent Ethic Committee) 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 or cytologically-proven NSCLC (squamous or non-squamous). If the
             diagnosis is cytologically-proven, sufficient material is necessary with at least 100
             tumor cells evaluated for PD-L1 IHC (Immunohistochemistry).

          3. PD-L1 expression ≥25% of tumor cells as assessed by the local pathology laboratory
             using protocols validated.

          4. Available tumor samples for centralized PD-L1 immunohistochemistry analysis.

          5. No EGFR (Epidermal Growth Factor Receptor) mutation and no ALK(Anaplasic Lymphoma
             Kinase) gene rearrangement.

          6. Stage IV (8th classification TNM) M1a or M1b or M1c with 3 or lower of metastatic
             organ sites on PET-CT (Positron Emission Tomography). Multiple lesions in a single
             organ are considered as one metastatic organ site. Any positive distant (non regional)
             lymph nodes were counted collectively as one metastatic organ site.

          7. ECOG (Eastern Cooperative Oncology Group) PS = 2 (in the first step) or 3 (in the
             second step) despite optimal symptomatic treatment.

          8. Body weight >30kg

          9. No prior systemic anticancer therapy (chemotherapy, immunotherapy including
             durvalumab, or EGFR or ALK inhibitors) given as primary therapy for advanced or
             metastatic disease. Neoadjuvant or adjuvant chemotherapy is not considered as
             chemotherapy for advanced or metastatic disease.

         10. Limited field of radiation for palliation within 2 weeks of the first dose of
             durvalumab is allowed, provided the lung is not in the radiation field and irradiated
             lesion(s) cannot be used as target lesions.

         11. Age 18-70 years.

         12. Measurable tumor disease by CT per Response Evaluation Criteria in Solid Tumors
             (RECIST) 1.1.

         13. Life expectancy > 8 weeks according to the investigator opinion.

         14. Adequate biological functions:

             neutrophils ≥ 1500/mm3 ; platelets ≥ 75 000/mm3 ; Hemoglobin ≥ 9 g/dL ; Creatinine
             Clearance > 40 mL/min , AST and ALT ≤ 2,5 ULN unless liver metastases are present, AST
             (aspartate aminotransferase) and ALT (alanine aminotransferase) ≤ 5 x ULN, serum
             bilirubin ≤ 1.5 x ULN except for patients with proved, Gilbert syndrome (≤ 5 x ULN) or
             patients with hepatic metastases (≤ 3 x ULN).

         15. Other investigations detailed in Section 5 must have been performed within the
             timelines indicated.

         16. Protocol treatment is to begin within 7 days of patient inclusion.

         17. Evidence of post-menopausal status or negative urinary or serum pregnancy test for
             female pre-menopausal patients. Women will be considered post-menopausal if they have
             been amenorrheic for 12 months without an alternative medical cause. The following
             age-specific requirements apply:

               -  Women <50 years of age would be considered post-menopausal if they have been
                  amenorrheic for 12 months or more following cessation of exogenous hormonal
                  treatments and if they have luteinizing hormone and follicle-stimulating hormone
                  levels in the post-menopausal range for the institution or underwent surgical
                  sterilization (bilateral oophorectomy or hysterectomy).

               -  Women ≥50 years of age would be considered post-menopausal if they have been
                  amenorrheic for 12 months or more following cessation of all exogenous hormonal
                  treatments, had radiation-induced menopause with last menses >1 year ago, had
                  chemotherapy-induced menopause with last menses >1 year ago, or underwent
                  surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or
                  hysterectomy).

         18. Females of childbearing potential who are sexually active with a nonsterilized male
             partner or men who are sexually active with women of childbearing potential must use a
             highly effective method of contraception prior the first dose of investigational
             product, and must agree to continue using such precautions for 90 days after the final
             dose of investigational product. Periodic abstinence, the rhythm method, and the
             withdrawal method are not acceptable methods of contraception.

        Exclusion Criteria:

          1. Pure or combined SCLC.

          2. Known HER2 (Human Epidermal Growth Factor Receptor), B-Raf, activating tumor
             mutations, or exon 14 c-MET splice mutations (mesenchymal-epithelial transition), or
             known ROS1 gene rearrangement.

          3. Asymptomatic or symptomatic brain metastasis.

          4. Carcinomatous meningitis.

          5. Active or prior documented autoimmune or inflammatory disorders (including
             inflammatory bowel disease [e.g., colitis or Crohn's disease], systemic lupus
             erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with
             polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The
             following are exceptions to this criterion:

               -  Patients with vitiligo or alopecia

               -  Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on
                  hormone replacement

               -  Any chronic skin condition that does not require systemic therapy

               -  Patients without active disease in the last 5 years may be included but only
                  after consultation with IFCT

               -  Patients with celiac disease controlled by diet alone

          6. Immunosuppressive treatment including systemic treatment with corticosteroids with
             greater dose than 10 mg prednisone equivalent daily, within 15 days before enrollment.
             Inhaled, nasal or topic corticosteroids are allowed.

          7. History of allogenic organ transplantation.

          8. Stage 4 (very severe, FEV1 (forced expiratory volume at one second) <30% predicted)
             chronic obstructive pulmonary disease (COPD) according to GOLD classification.

          9. NYHA (New York Heart Association) class 4 chronic heart failure

         10. Pre-existing interstitial lung.

         11. History of another primary malignancy except for :

               -  Malignancy treated with curative intent and with no known active disease ≥2 years
                  before the first dose of IP (Investigational Product) and of low potential risk
                  for recurrence

               -  Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
                  of disease

               -  Adequately treated carcinoma in situ without evidence of residual disease
                  Patients with a prostate adenocarcinoma history within the previous 5 years could
                  be included in case of localized prostate cancer.

         12. Living attenuated vaccine received within the 30 previous days.

         13. Received any other experimental treatment or participation to any other therapeutic
             clinical trial.

         14. Known allergy or hypersensitivity to any of the study drug or any of the study drug
             excipients.

         15. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment.
             Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone
             replacement therapy) is acceptable.

         16. Major surgical procedure within 28 days prior to the first dose of IP or planned
             surgical procedure during treatment.

         17. Uncontrolled intercurrent illness, including but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
             angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic
             gastrointestinal conditions associated with diarrhea, or psychiatric illness/social
             situations that would limit compliance with study requirement, substantially increase
             risk of incurring AEs (Adverse Events) or compromise the ability of the patient to
             give written informed consent.

         18. Active infection including tuberculosis, hepatitis B (known positive HBV surface
             antigen (HBsAg) result) and hepatitis C,. Patients with a past or resolved HBV
             infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence
             of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible
             only if polymerase chain reaction is negative for HCV RNA. History of active
             tuberculosis or evident primo-infection for which there is no record or evidence of an
             active anti-tuberculous treatment (please consult IFCT in case of doubt).

         19. Patient with human immunodeficiency virus (positive HIV ½ antibodies)

         20. Any condition that, in the opinion of investigator, could compromise the adherence to
             treatment and follow-up.

         21. Mental illness or psychological condition, which in the opinion of investigator could
             compromise the expression of the informed consent.

         22. No public health insurance.
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Proportion of patients experiencing Grade 3-5 Treatment Related Adverse Event at 8 weeks of durvalumab
Time Frame:8 weeks
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Incidence, type and severity of adverse event
Time Frame:From time of informed consent through treatment period (24 months) or up to 100 days post last dose of study treatment
Safety Issue:
Description:The maximum grade will be summarized by frequency and proportion of total patients, by system organ class and NCI-CTC, Version 5.0 categories.
Measure:Disease Control Rate
Time Frame:8 weeks
Safety Issue:
Description:Percentage of patients with objective response or stable disease according to RECIST 1.1 in the intent to treat population
Measure:Objective Response Rate according to BICR (Blinded Independent Central Review) and investigators
Time Frame:8 weeks (confirmed at 16 weeks)
Safety Issue:
Description:Percentage of patients with objective response according to RECIST 1.1 in the intent to treat population
Measure:Progression free survival
Time Frame:6 and 12 months
Safety Issue:
Description:Time between the date of durvalumab initiation and the first date of documented progression or death due to any cause, whichever occurs first.
Measure:Overall survival
Time Frame:6 and 12 months
Safety Issue:
Description:Time between the date of durvalumab initiation and the date of death due to any cause, whichever occurs first.
Measure:Performance status improvement rate
Time Frame:From time of randomisation through treatment period (24 months)
Safety Issue:
Description:Proportion of per-protocol patients whose PS during durvalumab treatment was improved from baseline
Measure:Evaluate the Quality of life
Time Frame:From time of randomisation through treatment period (24 months)
Safety Issue:
Description:EORTC QLQ-C30 +LC13 (Qualify of Life Questionnaire C30 + Lung Cancer 13) questionnaire
Measure:Centrally-assessed PD-L1 tumor expression Prognostic and predictive value
Time Frame:Baseline only
Safety Issue:
Description:
Measure:Evaluate the Quality of life
Time Frame:From time of randomisation through treatment period (24 months)
Safety Issue:
Description:EQ-5D (EuroQol 5 Dimensions) questionnaire

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Intergroupe Francophone de Cancerologie Thoracique

Trial Keywords

  • IFCT
  • Savimmune
  • Non small cell Lung Cancer
  • PS
  • Poor General condition
  • Lung Cancer
  • Durvalumab

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