Non Small Cell Lung Cancer
Conditions
Keywords
IFCT, NCSLC, atezolizumab, immunotherapy, chemotherapy
Brief summary
This is an open-label, randomized, non-comparative, multicentre, phase II study in which NSCLC patients who have progressed following chemotherapy and immunoptherapy are randomized to receive treatment with either paclitaxel and bevacizumab (Arm A), or paclitaxel, bevacizumab and atezolizumab (Arm B). An estimated 156 patients (52 in Arm A, 104 in Arm B) will be enrolled at approximately 40 centres. Patients will be treated until disease progression, unacceptable toxicity, withdrawal of consent or another discontinuation criterion is met. For patients in Arm B, continuation of atezolizumab beyond progression is permitted, at the investigator's discretion, if there is evidence of continued clinical benefit. The null hypothesis is progression free survival at 6 months ≤ 50% for Arm B, which is considered not sufficiently clinically meaningful to warrant further study. The alternative hypothesis is that 66% or more of patients in Arm B would achieve progression free survival at 6 months.
Interventions
DRUGPaclitaxel
Paclitaxel 200 mg/m² every 3 weeks
DRUGBevacizumab
Bevacizumab 15 mg/kg every 3 weeks
DRUGAtezolizumab
1200 mg every 3 weeks
Sponsors
Intergroupe Francophone de Cancerologie Thoracique
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients 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 patient care. Patients must be willing and able to comply with scheduled visits, treatment schedule, and laboratory testing. 2. Male or female aged at least 18 years old. 3. ECOG Performance Status of 0 or 1. 4. Histologically or cytologically documented locally advanced unresectable NSCLC (i.e. stage IIIB/IIIC not eligible for definitive chemo-radiotherapy) or metastatic NSCLC (i.e. Stage IV) (per the 8th edition of Union Internationale Contre le Cancer/American Joint Committee on Cancer \[UICC/AJCC\] staging system) of non-squamous histology. Note: patients with tumours of mixed histology must be classified as non-squamous or squamous based on the major histological component. 5. Patients progressing after treatment with immunotherapy (anti-PD-1 or anti-PD-L1 Ab) and a doublet of platinum-based chemotherapy, given concomitantly or sequentially to the exclusion of any other treatment. 6. Patients without contraindications to bevacizumab. 7. The investigator must confirm prior to enrolment that the patient has adequate tumour tissue available. Tumour biopsy should be exploitable for molecular analysis. Note: Tumour tissue collected after the patient was diagnosed with metastatic disease is preferred. Tumour tissue sample must not be from previously radiated locations. Tumour sample must be one block or at least 10 unstained slides of analysable tissue. If archival tissue is either insufficient or unavailable, the patient may still be eligible upon discussion with IFCT. 8. All patients must have at least one measurable target lesion according to RECIST v1.1. Previously irradiated lesions can only be considered measurable disease if disease progression has been unequivocally documented at that site since radiation and the previously irradiated lesion is not the only site of measurable disease. 9. Life expectancy ≥ 12 weeks 10. Adequate hematologic and end-organ function, defined by the following laboratory test results: * ANC ≥ 1500 cells/µL (without granulocyte colony-stimulating factor support within 14 days prior to C1D1). * WBC count ≥ 2500/µL. * Lymphocyte count ≥ 500/µL. * Platelet count ≥ 100 000/µL (without transfusion within 14 days prior to C1D1). * Haemoglobin ≥ 9.0 g/dL (patients may be transfused or receive erythropoietic treatment as per local standard of care). * Total bilirubin ≤ 1.5 x upper limit of normal (ULN). * Patients with known Gilbert's disease or hepatic metastasis who have serum bilirubin level ≤ 3 x ULN may be enrolled. * AST and ALT ≤ 3 x ULN, with the following exception: patients with documented liver metastases: AST and ALT ≤ 5 x ULN; ALP ≤ 2.5 x ULN; or patients with documented bone metastases: ALP ≤ 5 x ULN. * Serum albumin ≥ 2.5 g/dL. * aPTT or PTT and PT or INR ≤ 1.5 x ULN. This applies only to patients who are not receiving therapeutic anticoagulation. Patients receiving therapeutic anticoagulation should be on a stable dose for at least 1 week prior to C1D1. 11. Measured or calculated creatinine clearance ≥ 50 mL/min calculated using the local standard method. 12. Recovered from all toxicities associated with prior treatment, to acceptable baseline status, or NCI CTCAE v5.0 Grade 0 or 1, except for toxicities not considered a safety risk, such as alopecia or vitiligo. According to national (FITC) and international recommendations, certain severe immuno-induced toxicities are absolute
Exclusion criteria
for the (re)introduction of anti-PD-L1 antibodies (atezolizumab) (e.g. pneumopathy, colitis etc.). If in doubt, please contact the IFCT. 13. For women of childbearing potential (including women who have had a tubal ligation), serum pregnancy test must be performed and documented as negative within 14 days prior to C1D1. 14. Women of childbearing potential must remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods with a failure rate of \< 1% per year during the treatment period and for at least 6 months after the last dose of study drugs. Women must refrain from donating eggs during this same period. A woman is considered to be of childbearing potential if she is post-menarcheal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries or uterus). Examples of contraceptive methods with a failure rate of \<1% per year include bilateral tubal ligation, male sterilization, established proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. Hormonal contraceptive methods must be supplemented by a barrier method plus spermicide. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g. calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception. 15. Men with female partners of childbearing potential or pregnant female partners, must remain abstinent or use a condom during the treatment period and for at least 6 months after the last dose of study treatment to avoid exposing the embryo. Men must refrain from donating sperm during this same period. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g. calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception. 16. Participant has national health insurance coverage.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival at 6 months determined by independent reviewer | 6 months after randomization | PFS is defined as the time between the date of randomization and the first date of documented progression, as determined by independent review, or death due to any cause, whichever occurs first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | At progression, after an average of 15 months. | ORR is defined as the proportion of patients who have achieved a best overall response of complete response (CR) or partial response (PR) as determined by investigator review of radiographic disease assessments per RECIST v1.1. |
| Overall Survival | About 39 months | OS is defined as the time from date of inclusion to the date of death due to any cause. If a death has not been observed by the date of the analysis cut-off, OS will be censored at the date of last contact. |
| Progression Free Survival | At progression, after an average of 15 months. | PFS is defined as the time between the date of randomization and the first date of documented progression, as determined by investigator, or death due to any cause, whichever occurs first. |
| Incidence, nature, and severity of adverse events | From time of informed consent through treatment period and up to 30 days post last dose of study treatment (average of 15 months)] | Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0). |
| Overall health status | At progression, after an average of 15 months. | Overall health status will also be assessed using the EuroQol 5-dimension 5-level (EQ-5D-5L) questionnaire. |
| Time until definitive health related quality of life score deterioration | From enrollment to score deterioration, after an average of 15 months. | The time until definitive health related quality of life score deterioration will be analysed using the EORTC Core Quality of Life Questionnaire (QLQ-C30). |
Countries
France
Outcome results
None listed