Trial Title:
Combination of Paclitaxel-bevacizumab ± Atezolizumab in Patients with Advanced NSCLC Progressing After Immunotherapy & Chemotherapy
NCT ID:
NCT05781308
Condition:
Non Small Cell Lung Cancer
Conditions: Official terms:
Carcinoma, Non-Small-Cell Lung
Paclitaxel
Bevacizumab
Atezolizumab
Conditions: Keywords:
IFCT
NCSLC
atezolizumab
immunotherapy
chemotherapy
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Active, not recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Paclitaxel
Description:
Paclitaxel 200 mg/m² every 3 weeks
Arm group label:
Arm A: paclitaxel + bevacizumab
Arm group label:
Arm B: paclitaxel + bevacizumab + atezolizumab
Intervention type:
Drug
Intervention name:
Bevacizumab
Description:
Bevacizumab 15 mg/kg every 3 weeks
Arm group label:
Arm A: paclitaxel + bevacizumab
Arm group label:
Arm B: paclitaxel + bevacizumab + atezolizumab
Other name:
Avastin
Intervention type:
Drug
Intervention name:
Atezolizumab
Description:
1200 mg every 3 weeks
Arm group label:
Arm B: paclitaxel + bevacizumab + atezolizumab
Other name:
Tecentriq
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.
Criteria for eligibility:
Criteria:
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.
Exclusion Criteria:
1. Known molecular alteration of EGFR, ALK, ROS1, RET, NTRK, MET, NRG1.
2. Patients previously treated by bevacizumab combined with first-line chemotherapy for
NSCLC.
3. Patients with a previous treatment by taxane (docetaxel, paclitaxel). A patient with
a previous treatment by peri-operative taxane or in association with radiotherapy is
eligible if the treatment has been stopped for more than 6 months.
4. Patients previously treated for unresectable stage III NSCLC are not eligible if
they progressed during or within 6 months of stopping consolidation immunotherapy.
Patients previously treated by peri-operative immunotherapy for stage I, II or III
NSCLC are not eligible.
5. Patients with symptomatic brain metastasis, leptomeningeal disease or other active
CNS metastases are not eligible. Note: patients with previously treated or untreated
brain metastases may participate, provided they are stable (e.g. without evidence of
progression by radiographic imaging for at least 28 days before the first dose of
study treatment and neurologic symptoms have returned to baseline). Patients must
have no evidence of new or enlarging brain metastases or CNS oedema. Patients must
have discontinued use of steroids (with a dose > 10 mg prednisone equivalent daily)
at least 7 days before the first dose of study treatment.
6. Spinal cord compression not definitively treated with surgery or radiation, or
previously diagnosed and treated spinal cord compression without evidence that
disease has been clinically stable for ≥ 2 weeks prior to screening.
7. Malignancies other than NSCLC within 3 years prior to randomization, with the
exception of those with a negligible risk of metastasis or death, or treated with
expected curative outcome (such as adequately treated in situ cervical cancer, basal
or squamous cell skin cancer, localized prostate cancer, ductal carcinoma in situ,
or stage I uterine cancer).
8. Inability to comply with study or follow-up procedures.
9. Pregnant, lactating, or breastfeeding women.
10. Severe infections (including active tuberculosis) within 4 weeks prior to initiation
of study treatment, including but not limited to hospitalization for complications
of infection, bacteraemia, or severe pneumonia.
11. Received oral or IV antibiotics (including antifungals) within 2 weeks prior to
randomization. Patients receiving prophylactic antibiotics (e.g. for prevention of a
urinary tract infection or chronic obstructive pulmonary disease exacerbations) are
eligible.
12. Major surgical procedure within 4 weeks prior to randomization, or anticipation of
need for a major surgical procedure during the course of the study.
13. Inability to understand the local language (French).
14. Any disease, metabolic dysfunction, physical examination finding, or clinical
laboratory finding giving reasonable suspicion of a disease or condition that
contraindicates the use of an investigational drug, that may affect the
interpretation of the results, or that may render the patient at high risk from
treatment complications.
15. History of severe allergic, anaphylactic, or other hypersensitivity reactions to
chimeric or humanized antibodies or fusion proteins.
16. Known hypersensitivity or allergy to Chinese hamster ovary cell products or any
component of the atezolizumab formulation.
17. Active or history of autoimmune disease with the following exceptions:
- Patients with a history of autoimmune-related hypothyroidism on a stable dose
of thyroid replacement hormone may be eligible for this study following
discussion with IFCT.
- Patients with controlled type 1 diabetes mellitus on a stable insulin regimen
may be eligible for this study following discussion with IFCT.
- Patients with benign rheumatoid polyarthritis not needing any immunosuppressive
systemic treatment.
- 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 they meet the following conditions:
- Rash must cover less than 10% of body surface area (BSA).
- Disease is well controlled at baseline and only requires low potency
topical steroids.
- No acute exacerbations of the underlying condition within the last 12
months requiring treatment with either PUVA (psoralen plus ultraviolet A
radiation), methotrexate, retinoids, biologic agents, oral calcineurin
inhibitors, or high potency or oral steroids.
18. Prior allogeneic bone marrow transplantation or prior solid organ transplantation.
19. History of idiopathic pulmonary fibrosis (including pneumonitis), organizing
pneumonia (i.e. bronchiolitis obliterans, cryptogenic organizing pneumonia), drug
induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on
chest computed tomography (CT) scan at screening. History of radiation pneumonitis
in the radiation field (fibrosis) is permitted.
20. Patients with a known history of a positive test for HIV or known AIDS who have not
received effective antiretroviral therapy (ART) for the last 4 weeks and who have an
HIV viral load >200 copies/mL, regardless of CD4+ T-cell count.
21. Patients with known acute viral hepatitis B or C (HBV, HBC) according to serological
tests. Patients with serological sequalae of cured viral hepatitis are eligible.
22. Administration of live, attenuated vaccine within 4 weeks prior to initiation of
study treatment or anticipation that such a live attenuated vaccine will be required
during the study. Influenza vaccination should be given during influenza season
only. Patients must not receive live, attenuated influenza vaccine within 4 weeks
prior to enrolment or at any time during the study, and for 5 months following the
last study treatment.
23. Treatment with systemic corticosteroids or other systemic immunosuppressive
medications (including but not limited to prednisone > 10 mg/day, cyclophosphamide,
azathioprine, methotrexate, thalidomide, and tumour necrosis factor [TNF-α]
antagonists) within 2 weeks prior to randomization. Patients who have received
acute, low dose, systemic immunosuppressant medications (e.g. a one-time dose of
dexamethasone for nausea) may be eligible for this study following discussion with
IFCT. The use of inhaled corticosteroids is allowed. The use of mineralocorticoids
(e.g. fludrocortisone) for patients with orthostatic hypotension is allowed.
Physiologic doses of corticosteroids for adrenal insufficiency may be allowed after
discussion with IFCT.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
CHU Amiens
Address:
City:
Amiens
Country:
France
Facility:
Name:
CHU d'Angers
Address:
City:
Angers
Zip:
49033
Country:
France
Facility:
Name:
CH Avignon
Address:
City:
Avignon
Country:
France
Facility:
Name:
CH Côte Basque
Address:
City:
Bayonne
Country:
France
Facility:
Name:
CHU Besançon - Hôpital J. MINJOZ
Address:
City:
Besançon
Zip:
25030
Country:
France
Facility:
Name:
Polyclinique Bordeaux Nord Aquitaine
Address:
City:
Bordeaux
Country:
France
Facility:
Name:
Hôpital APHP Ambroise Paré
Address:
City:
Boulogne
Zip:
92104
Country:
France
Facility:
Name:
CHU Côte de Nacre
Address:
City:
Caen
Zip:
14000
Country:
France
Facility:
Name:
CH Cholet
Address:
City:
Cholet
Country:
France
Facility:
Name:
CHU Gabriel Montpied
Address:
City:
Clermont-Ferrand
Country:
France
Facility:
Name:
CH Pasteur
Address:
City:
Colmar
Country:
France
Facility:
Name:
Centre Hospitalier Intercommunal Créteil CHIC
Address:
City:
Créteil
Country:
France
Facility:
Name:
Centre Georges-François Leclerc
Address:
City:
Dijon
Zip:
21079
Country:
France
Facility:
Name:
CHU Dijon
Address:
City:
Dijon
Country:
France
Facility:
Name:
Chu Grenoble
Address:
City:
Grenoble
Zip:
38043
Country:
France
Facility:
Name:
CHD Vendée
Address:
City:
La Roche-sur-yon
Country:
France
Facility:
Name:
CH Versailles
Address:
City:
Le Chesnay
Country:
France
Facility:
Name:
CH Le Mans
Address:
City:
Le Mans
Country:
France
Facility:
Name:
CHU Lille
Address:
City:
Lille
Country:
France
Facility:
Name:
CHU Limoges
Address:
City:
Limoges
Zip:
87042
Country:
France
Facility:
Name:
Centre Léon Bérard
Address:
City:
Lyon
Zip:
69373
Country:
France
Facility:
Name:
Institut Paoli Calmettes
Address:
City:
Marseille
Zip:
13273
Country:
France
Facility:
Name:
APHM Hôpital Nord
Address:
City:
Marseille
Country:
France
Facility:
Name:
Hôpital Européen
Address:
City:
Marseille
Country:
France
Facility:
Name:
Hôpitaux Privés de Metz Robert Schuman
Address:
City:
Metz
Country:
France
Facility:
Name:
GHR Mulhouse et Sud Alsace GHRMSA
Address:
City:
Mulhouse
Zip:
68070
Country:
France
Facility:
Name:
CHR Orléans
Address:
City:
Orléans
Country:
France
Facility:
Name:
Hôpital BICHAT
Address:
City:
Paris
Zip:
75877
Country:
France
Facility:
Name:
Hôpital TENON
Address:
City:
Paris
Zip:
75970
Country:
France
Facility:
Name:
Groupe Hospitalier Paris Saint Joseph GHPSJ
Address:
City:
Paris
Country:
France
Facility:
Name:
CH Pau
Address:
City:
Pau
Country:
France
Facility:
Name:
CHU Bordeaux Haut-Lévèque
Address:
City:
Pessac
Country:
France
Facility:
Name:
Hospices Civils de Lyon - URCOT
Address:
City:
Pierre-Bénite
Country:
France
Facility:
Name:
CHU Poitiers
Address:
City:
Poitiers
Country:
France
Facility:
Name:
CH Annecy Genevois
Address:
City:
Pringy
Country:
France
Facility:
Name:
CHU Rouen
Address:
City:
Rouen
Zip:
76031
Country:
France
Facility:
Name:
Institut de Cancerologie de l'Ouest ICO
Address:
City:
Saint-Herblain
Country:
France
Facility:
Name:
CHU Saint Etienne
Address:
City:
Saint-Étienne
Country:
France
Facility:
Name:
Nouvel Hôpital Civil - Hôpitaux Universitaires de Strasbourg
Address:
City:
Strasbourg
Zip:
67091
Country:
France
Facility:
Name:
HIA Sainte-Anne
Address:
City:
Toulon
Zip:
83800
Country:
France
Facility:
Name:
CHU Toulouse
Address:
City:
Toulouse
Zip:
31059
Country:
France
Facility:
Name:
CHU Tours
Address:
City:
Tours
Country:
France
Facility:
Name:
Clinique Teissier
Address:
City:
Valenciennes
Country:
France
Facility:
Name:
CH Villefranche Nord Ouest
Address:
City:
Villefranche-sur-Saône
Zip:
69655
Country:
France
Start date:
April 26, 2023
Completion date:
June 2026
Lead sponsor:
Agency:
Intergroupe Francophone de Cancerologie Thoracique
Agency class:
Other
Source:
Intergroupe Francophone de Cancerologie Thoracique
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05781308
https://www.ifct.fr/
