Combination of Paclitaxel-bevacizumab ± Atezolizumab in Patients With Advanced NSCLC Progressing After Immunotherapy & Chemotherapy

NCT05781308 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: IFCT-2201
• Study Type: interventional
• Target: 156
• Locations: 1 country
• Sites: 44

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.

Conditions

Non Small Cell Lung Cancer

Keywords

IFCT; NCSLC; atezolizumab; immunotherapy; chemotherapy

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival at 6 months determined by independent reviewer

  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.

  6 months after randomization

Secondary Outcomes (6)

• Progression Free Survival

  At progression, after an average of 15 months.

• Objective Response Rate

  At progression, after an average of 15 months.

• Overall Survival

  About 39 months

• Time until definitive health related quality of life score deterioration

  From enrollment to score deterioration, after an average of 15 months.

• 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)]

Study Arms (2)

Arm A: paclitaxel + bevacizumab

OTHER

Bevacizumab 15 mg/kg and paclitaxel 200 mg/m² intravenously every three weeks until progression.

Drug: Paclitaxel; Drug: Bevacizumab

Arm B: paclitaxel + bevacizumab + atezolizumab

EXPERIMENTAL

Atezolizumab 1200 mg, bevacizumab 15 mg/kg and paclitaxel 200 mg/m² intravenously every three weeks until progression.

Drug: Paclitaxel; Drug: Bevacizumab; Drug: Atezolizumab

Interventions

Paclitaxel DRUG

Paclitaxel 200 mg/m² every 3 weeks

Arm A: paclitaxel + bevacizumab; Arm B: paclitaxel + bevacizumab + atezolizumab

Bevacizumab DRUG

Bevacizumab 15 mg/kg every 3 weeks

Also known as: Avastin

Arm A: paclitaxel + bevacizumab; Arm B: paclitaxel + bevacizumab + atezolizumab

Atezolizumab DRUG

1200 mg every 3 weeks

Also known as: Tecentriq

Arm B: paclitaxel + bevacizumab + atezolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Male or female aged at least 18 years old.
• ECOG Performance Status of 0 or 1.
• 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.
• Patients without contraindications to bevacizumab.
• 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.
• 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.
• Life expectancy ≥ 12 weeks
• 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).

You may not qualify if:

• 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.
• 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.
• 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.
• Participant has national health insurance coverage.
• Known molecular alteration of EGFR, ALK, ROS1, RET, NTRK, MET, NRG1.
• Patients previously treated by bevacizumab combined with first-line chemotherapy for NSCLC.
• 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.
• 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.
• 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.
• 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.
• 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).
• Inability to comply with study or follow-up procedures.
• Pregnant, lactating, or breastfeeding women.
• 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.
• 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.

Sponsors & Collaborators

• Intergroupe Francophone de Cancerologie Thoracique: lead

Study Sites (44)

CHU Amiens

Amiens, France

Location

CHU d'Angers

Angers, 49033, France

Location

CH Avignon

Avignon, France

Location

CH Côte Basque

Bayonne, France

Location

CHU Besançon - Hôpital J. MINJOZ

Besançon, 25030, France

Location

Polyclinique Bordeaux Nord Aquitaine

Bordeaux, France

Location

Hôpital APHP Ambroise Paré

Boulogne, 92104, France

Location

CHU Côte de Nacre

Caen, 14000, France

Location

CH Cholet

Cholet, France

Location

CHU Gabriel Montpied

Clermont-Ferrand, France

Location

CH Pasteur

Colmar, France

Location

Centre Hospitalier Intercommunal Créteil CHIC

Créteil, France

Location

Centre Georges-François Leclerc

Dijon, 21079, France

Location

CHU Dijon

Dijon, France

Location

Chu Grenoble

Grenoble, 38043, France

Location

CHD Vendée

La Roche-sur-Yon, France

Location

CH Versailles

Le Chesnay, France

Location

CH Le Mans

Le Mans, France

Location

CHU Lille

Lille, France

Location

CHU Limoges

Limoges, 87042, France

Location

Centre Léon Bérard

Lyon, 69373, France

Location

Institut Paoli Calmettes

Marseille, 13273, France

Location

APHM Hôpital Nord

Marseille, France

Location

Hôpital Européen

Marseille, France

Location

Hôpitaux Privés de Metz Robert Schuman

Metz, France

Location

GHR Mulhouse et Sud Alsace GHRMSA

Mulhouse, 68070, France

Location

CHR Orléans

Orléans, France

Location

Hôpital BICHAT

Paris, 75877, France

Location

Hôpital TENON

Paris, 75970, France

Location

Groupe Hospitalier Paris Saint Joseph GHPSJ

Paris, France

Location

CH Pau

Pau, France

Location

CHU Bordeaux Haut-Lévèque

Pessac, France

Location

Hospices Civils de Lyon - URCOT

Pierre-Bénite, France

Location

CHU Poitiers

Poitiers, France

Location

CH Annecy Genevois

Pringy, France

Location

CHU Rouen

Rouen, 76031, France

Location

CHU Saint Etienne

Saint-Etienne, France

Location

Institut de Cancerologie de l'Ouest ICO

Saint-Herblain, France

Location

Nouvel Hôpital Civil - Hôpitaux Universitaires de Strasbourg

Strasbourg, 67091, France

Location

HIA Sainte-Anne

Toulon, 83800, France

Location

CHU Toulouse

Toulouse, 31059, France

Location

CHU Tours

Tours, France

Location

Clinique Teissier

Valenciennes, France

Location

CH Villefranche Nord Ouest

Villefranche-sur-Saône, 69655, France

Location

Related Links

• IFCT website

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Paclitaxel; Bevacizumab; atezolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Arnaud SCHERPEREEL, Pr

  Institut Coeur Poumon CHU de Lille

  PRINCIPAL INVESTIGATOR

• Etienne GIROUX-LEPRIEUR, Pr

  Pulmonology & Thoracic Oncology Department APHP - Hôpital Ambroise Paré

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2023
• First Posted: March 23, 2023
• Study Start: April 26, 2023
• Primary Completion: June 2, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: November 18, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share

Locations

FR (44)