Informations générales (source: ClinicalTrials.gov)
Maintenance Pembrolizumab at Usual or Low doSE in Non-squamous Lung Cancer: a Non-inferiority Study (Pulse)
Interventional
Phase 3
Gustave Roussy, Cancer Campus, Grand Paris (Voir sur ClinicalTrials)
mars 2023
janvier 2029
05 décembre 2024
Pulse is a randomized non-inferiority phase III clinical trial assessing a new mode of
immunotherapy administration based on increased interval time between 2 infusions as
maintenance treatment in Pulse arm compared with the conventional administration in
Control arm.
In both treatment arms, pembrolizumab alone or combined with pemetrexed is allowed as
maintenance treatment. Indeed :
In Pulse arm : Pembrolizumab 200 mg will be administered to patients every 6 weeks (Q6W)
plus, in the absence of contra-indication pemetrexed 500 mg/m^2 will be administered
every 3 weeks (Q3W).
In control arm : Pembrolizumab 200 mg will be administered to patients every 3 weeks
(Q3W) or 400 mg every 6 weeks plus,in the absence of contra-indication pemetrexed 500
mg/m^2 will be administered every 3 weeks (Q3W).
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | Benjamin BESSE | 18/03/2024 11:06:04 | Contacter | ||
| HOPITAL FOCH | ANNE CECILE METIVIER | 07/04/2025 07:02:30 | Contacter | ||
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| AP-HP - Hôpital Cochin | WISLEZ Marie, MD | Contact (sur clinicalTrials) | |||
| AP-HP - Hôpital Tenon | CADRANEL Jacques, MD | Contact (sur clinicalTrials) | |||
| CHI DE CRETEIL | MONNET Isabelle, MD | Contact (sur clinicalTrials) | |||
| GH PARIS SITE SAINT JOSEPH | NALTET Charles, MD | Contact (sur clinicalTrials) | |||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre Hospitalier d'Auxerre - 89000 - Auxerre - Yonne - France | MARTI Adina, MD | Contact (sur clinicalTrials) | |||
| Centre Hospitalier de Béziers - 34500 - Béziers - Hérault - France | HAOUACHI Rym, MD | Contact (sur clinicalTrials) | |||
| Centre Hospitalier de Bigorre - 65000 - Tarbes - Hautes-Pyrénées - France | DEGUIRAL Philippe, MD | Contact (sur clinicalTrials) | |||
| Centre Hospitalier de Carcassonne - 11810 - Carcassonne - Aude - France | LABOUREY Jean Luc, MD | Contact (sur clinicalTrials) | |||
| Centre Hospitalier de Cholet - 49300 - Cholet - Maine-et-Loire - France | GUILLEMOIS Sylvère, MD | Contact (sur clinicalTrials) | |||
| Centre Hospitalier de la Côte Basque - 64100 - Bayonne - Pyrénées-Atlantiques - France | SCHNEIDER Sophie, MD | Contact (sur clinicalTrials) | |||
| Centre Hospitalier de Saint-Malo - 35400 - Saint-Malo - Ille-et-Vilaine - France | TIERCIN Marie, MD | Contact (sur clinicalTrials) | |||
| Centre Hospitalier des Pays de Morlaix - 29600 - Morlaix - Finistère - France | AMRANE Karim, MD | Contact (sur clinicalTrials) | |||
| Centre Hospitalier Intercommunal de Compiègne-Noyon - 60200 - Compiègne - Oise - France | DEHETTE Stéphanie, MD | Contact (sur clinicalTrials) | |||
| Centre Hospitalier Régional d'Orléans - NHO - 45067 - Orléans - Loiret - France | DIXMIER Adrien, MD | Contact (sur clinicalTrials) | |||
| Centre Hospitalier Régional Universitaire de Brest (Hôpital Morvan) - 29609 - Brest - Finistère - France | QUERE Gilles, MD | Contact (sur clinicalTrials) | |||
| Centre Hospitalier Régional Universitaire de Tours - 37044 - Tours - Indre-et-Loire - France | CARMIER Delphine, MD | Contact (sur clinicalTrials) | |||
| Centre Hospitalier Universitaire - La Réunion - Site Felix Guyon - 97400 - Saint-Denis - La Réunion - France | GAZAILLE Virgile, MD | Contact (sur clinicalTrials) | |||
| Centre Hospitalier Universitaire - La Réunion - Site Sud - 97448 - Saint-Pierre - La Réunion - France | HUCHOT Eric, MD | Contact (sur clinicalTrials) | |||
| CHU Rennes - 35000 - Rennes - Ille-et-Vilaine - France | RICORDEL Charles, MD | Contact (sur clinicalTrials) | |||
| CHU St-Etienne - 42270 - Saint Priest en Jarez - Loire - France | FOURNEL Pierre, MD | Contact (sur clinicalTrials) | |||
| Clinique Sainte Anne - Strasbourg - 67000 - Strasbourg - Bas-Rhin - France | TAZI Youssef, MD | Contact (sur clinicalTrials) | |||
| Groupe Hospitalier de la Région de Mulhouse et Sud Alsace - 68100 - Mulhouse - Haut-Rhin - France | DEBIEUVRE Dédier, MD | Contact (sur clinicalTrials) | |||
| Groupe Hospitalier La Rochelle - 17000 - La Rochelle - Charente-Maritime - France | LEVRAT Virginie, MD | Contact (sur clinicalTrials) | |||
| Hôpital d'Instruction des Armées Bégin - 94160 - Saint-Mandé - Val-de-Marne - France | HELISSEY Carole, MD | Contact (sur clinicalTrials) | |||
| Hôpital Européen de Marseille - 13003 - Marseille - Bouches-du-Rhône - France | LE TREUT Jacques, md | Contact (sur clinicalTrials) | |||
| Hôpital Pitié-Salpêtrière - APHP - 75013 - Paris - France | SPANO Jean-Philippe, MD | Contact (sur clinicalTrials) | |||
| Hospices Civils de Lyon - Hôpital Louis Pradel - 69677 - Bron - Lyon - France | DURUISSEAUX Michaël, MD | Contact (sur clinicalTrials) | |||
| Institut de Cancérologie Strasbourg Europe (ICANS) - 67200 - Strasbourg - Bas-Rhin - France | SCHOTT Rolland, MD | Contact (sur clinicalTrials) | |||
Critères
Tous
Inclusion Criteria:
A) To be checked before the induction phase (only for patient included before induction
phase) :
1. Histologically or cytologically confirmed diagnosis of non-squamous non-small cell
lung cancer (NSCLC).
2. Non-operable / non-irradiable stage III or stage IV.
3. Patient must be eligible to receive 3 or 4 cycles of induction treatment combination
with pembrolizumab plus platinum (cisplatin or carboplatin) and pemetrexed.
4. In the presence of an EGFR mutation, an ALK or ROS1 rearrangement the patient must
have received at least one specific targeted therapy line.
5. Age ≥ 18 years old.
6. Performance status 0 or 1.
7. Signed informed consent.
8. Patient affiliated to a social security system or beneficiary of the same.
B) To be checked before the maintenance phase (for all patient) :
1. Histologically or cytologically confirmed diagnosis of non-squamous non-small cell
lung cancer (NSCLC).
2. Non-operable / non-irradiable stage III or stage IV.
3. Received 3 or 4 cycles of induction treatment combination with pembrolizumab plus
platinum (cisplatin or carboplatin) and pemetrexed.
4. Patient must be eligible to receive maintenance pembrolizumab with or without
pemetrexed, last induction chemotherapy cycle within 42 days before randomization.
5. Stable disease, partial or complete response according to RECIST 1.1 criteria after
induction chemotherapy and pembrolizumab. Targets lesions are not required before
randomization.
6. In the presence of an EGFR mutation, an ALK or ROS1 rearrangement the patient must
have received at least one specific targeted therapy line (not needed a second time
if already checked before induction phase).
7. Patients with baseline brain metastases will be eligible in case of stability or no
evidence of progression and if they remain clinically stable.
8. Age ≥ 18 years old.
9. Performance status 0 or 1.
10. Signed informed consent (only for patient included after induction phase).
11. Patient affiliated to a social security system or beneficiary of the same.
12. Creatinine clearance > 30 ml/min by Cockcroft-Gault* or MDRD in case that patient
will start maintenance just with pembrolizumab but ≥ 45 ml/min if the patient will
receive pemetrexed plus pembrolizumab.
*Cockcroft- Gault Formula:
- Female CrCl = [(140 - age in years) x weight in kg x 0.85] / 72 x serum
creatinine in mg/dL;
- Male CrCl = [(140 - age in years) x weight in kg x 1.00] /72 x serum creatinine
in mg/dL.
13. Neutrophils ≥ 1500/μL and platelets ≥ 100 000/μL.
14. Bilirubin ≤ 1.5 upper limit normal (ULN).
15. Transaminases, Alkaline phosphatase ≤ 2.5 x the ULN except in case of liver
metastases (5 x ULN).
16. Patients might have received platinum-based chemotherapy as an adjuvant or
neoadjuvant treatment, or with radiotherapy for a localized lung cancer, provided
that the chemotherapy was ended more than 6 months before the first cycle of
induction chemotherapy.
17. Patients might have received previous immune checkpoint inhibitors as an adjuvant or
neoadjuvant treatment, or as a consolidation treatment after radiotherapy for a
localized lung cancer, but the immune checkpoint inhibitors must be finished at
least than 12 months before the first cycle of induction chemotherapy for advanced
stage.
18. A woman is eligible for the study if she is no longer likely to procreate
(physiologically unfit to carry out a pregnancy), which includes women who have had:
a hysterectomy, an oophorectomy, a bilateral tubal ligation.
Post-menopausal women:
- Patients not using hormone replacement therapy should have had a complete
cessation of menstruation for at least one year and be over 40 years of age,
or, if in doubt, have an FSH (Follicle Stimulating Hormone) level > 40 mIU/mL
and an estradiol level < 40 pg/mL (< 150 pmol/L).
- Patients using hormone replacement therapy must have had a complete cessation
of menstruation for at least one year and be over 45 years of age or have
evidence of menopause (FSH and estradiol levels) before starting hormone
replacement therapy.
19. Women who are likely to procreate are eligible if they have a negative serum
pregnancy test in the week before the first dose of treatment and preferably as
close as possible to the first dose and if they agree to use an effective
contraceptive method during the course of the study through 4 months after the last
dose of study medication.
Sexually active males patients must agree to use condom during the study and for at least
4 months after the last study treatment administration. Also, it is recommended their
women of childbearing potential partner use a highly effective method of contraception.
A) To be checked before the induction phase (only for patient included before induction
phase) :
1. Histologically or cytologically confirmed diagnosis of non-squamous non-small cell
lung cancer (NSCLC).
2. Non-operable / non-irradiable stage III or stage IV.
3. Patient must be eligible to receive 3 or 4 cycles of induction treatment combination
with pembrolizumab plus platinum (cisplatin or carboplatin) and pemetrexed.
4. In the presence of an EGFR mutation, an ALK or ROS1 rearrangement the patient must
have received at least one specific targeted therapy line.
5. Age ≥ 18 years old.
6. Performance status 0 or 1.
7. Signed informed consent.
8. Patient affiliated to a social security system or beneficiary of the same.
B) To be checked before the maintenance phase (for all patient) :
1. Histologically or cytologically confirmed diagnosis of non-squamous non-small cell
lung cancer (NSCLC).
2. Non-operable / non-irradiable stage III or stage IV.
3. Received 3 or 4 cycles of induction treatment combination with pembrolizumab plus
platinum (cisplatin or carboplatin) and pemetrexed.
4. Patient must be eligible to receive maintenance pembrolizumab with or without
pemetrexed, last induction chemotherapy cycle within 42 days before randomization.
5. Stable disease, partial or complete response according to RECIST 1.1 criteria after
induction chemotherapy and pembrolizumab. Targets lesions are not required before
randomization.
6. In the presence of an EGFR mutation, an ALK or ROS1 rearrangement the patient must
have received at least one specific targeted therapy line (not needed a second time
if already checked before induction phase).
7. Patients with baseline brain metastases will be eligible in case of stability or no
evidence of progression and if they remain clinically stable.
8. Age ≥ 18 years old.
9. Performance status 0 or 1.
10. Signed informed consent (only for patient included after induction phase).
11. Patient affiliated to a social security system or beneficiary of the same.
12. Creatinine clearance > 30 ml/min by Cockcroft-Gault* or MDRD in case that patient
will start maintenance just with pembrolizumab but ≥ 45 ml/min if the patient will
receive pemetrexed plus pembrolizumab.
*Cockcroft- Gault Formula:
- Female CrCl = [(140 - age in years) x weight in kg x 0.85] / 72 x serum
creatinine in mg/dL;
- Male CrCl = [(140 - age in years) x weight in kg x 1.00] /72 x serum creatinine
in mg/dL.
13. Neutrophils ≥ 1500/μL and platelets ≥ 100 000/μL.
14. Bilirubin ≤ 1.5 upper limit normal (ULN).
15. Transaminases, Alkaline phosphatase ≤ 2.5 x the ULN except in case of liver
metastases (5 x ULN).
16. Patients might have received platinum-based chemotherapy as an adjuvant or
neoadjuvant treatment, or with radiotherapy for a localized lung cancer, provided
that the chemotherapy was ended more than 6 months before the first cycle of
induction chemotherapy.
17. Patients might have received previous immune checkpoint inhibitors as an adjuvant or
neoadjuvant treatment, or as a consolidation treatment after radiotherapy for a
localized lung cancer, but the immune checkpoint inhibitors must be finished at
least than 12 months before the first cycle of induction chemotherapy for advanced
stage.
18. A woman is eligible for the study if she is no longer likely to procreate
(physiologically unfit to carry out a pregnancy), which includes women who have had:
a hysterectomy, an oophorectomy, a bilateral tubal ligation.
Post-menopausal women:
- Patients not using hormone replacement therapy should have had a complete
cessation of menstruation for at least one year and be over 40 years of age,
or, if in doubt, have an FSH (Follicle Stimulating Hormone) level > 40 mIU/mL
and an estradiol level < 40 pg/mL (< 150 pmol/L).
- Patients using hormone replacement therapy must have had a complete cessation
of menstruation for at least one year and be over 45 years of age or have
evidence of menopause (FSH and estradiol levels) before starting hormone
replacement therapy.
19. Women who are likely to procreate are eligible if they have a negative serum
pregnancy test in the week before the first dose of treatment and preferably as
close as possible to the first dose and if they agree to use an effective
contraceptive method during the course of the study through 4 months after the last
dose of study medication.
Sexually active males patients must agree to use condom during the study and for at least
4 months after the last study treatment administration. Also, it is recommended their
women of childbearing potential partner use a highly effective method of contraception.
A) To be checked before the induction phase (only for patient included before induction
phase) :
1. Mixed small-cell, squamous-cell carcinoma.
2. Mental or psychological illness that does not allow the patient to give informed
consent.
3. Pregnant or breastfeeding women.
4. History of HIV or chronic hepatitis B or C.
5. Active or uncontrolled infection.
6. History of one or more of the following cardiovascular disorders in the previous 6
months:
- Coronary artery bypass or peripheral arterial bypass, cardiac angioplasty or
stent.
- Myocardial infarction
- Severe or unstable angina pectoris
- Peripheral vascular disease, pulmonary embolism or untreated thromboembolic
events, stroke or transient ischemic attack. Note: Patients with recent deep
vein thrombosis (including pulmonary embolism) treated with anticoagulant for
at least 4 weeks and clinically stable are eligible.
- Congestive heart failure class III or IV as defined by the NYHA
7. Concomitant treatment with another experimental treatment or participation in
another clinical trial.
B) To be checked before the maintenance phase (for all patient) :
1. Presence of grade 3 or 4 toxicity related to pembrolizumab limiting maintenance
treatment continuation.
2. Mixed small-cell, squamous-cell carcinoma.
3. Corticosteroids at a dose greater than 20 mg per day of prednisone or equivalent.
4. Patient unable to follow the therapeutic program.
5. Mental or psychological illness that does not allow the patient to give informed
consent.
6. Pregnant or breastfeeding women.
7. Ongoing immunosuppressive systemic therapy (cyclophosphamide, aziatropin,
methotrexate, thalidomide and anti-TNF).
8. Active autoimmune diseases. History of autoimmune diseases including myasthenia
gravis, lupus erythematosus, rheumatoid arthritis, irritable bowel syndrome,
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
hypothyroidism treated with a stable dose of hormone replacement therapy are
eligible. Patients with diabetes treated with insulin are eligible.
9. History of idiopathic pulmonary fibrosis, organized pneumonia (i.e., obliterating
bronchiolitis), drug-induced lung disease or active signs of pneumonia, pulmonary
infiltration (regardless of cause) detected on the baseline chest CT-scan.
10. History of any other hematologic or primary solid tumor malignancy unless in
remission for at least 2 years and without specific treatment (as example, not
allowed hormonal therapy to replace for breast cancer or hormonal therapy
substitution in prostate cancer). pT1-2 prostatic cancer Gleason score < 6,
superficial bladder cancer, non-melanoma skin cancer or carcinoma in situ of the
cervix are allowed.
11. Presence of a condition or condition that makes patient participation in the study
inappropriate, including serious unresolved or unstable toxicities from previous
administration of another experimental treatment or any medical condition that could
interfere with patient safety, obtaining consent or compliance with study
procedures.
12. Administration of a live attenuated vaccine within the 4 weeks before day 1 of Cycle
1 or administration of a live attenuated vaccine planned for the duration of the
study. The flu vaccine can be given during the flu season (approximately from
October to May). Patients should not receive a live attenuated influenza vaccine
during the 4 weeks preceding day 1 of Cycle 1 and should not receive this type of
vaccine during the study.
13. History of HIV or chronic hepatitis B or C (not needed a second time if already
checked before induction phase).
14. Active or uncontrolled infection.
15. History of one or more of the following cardiovascular disorders in the previous 6
months:
- Coronary artery bypass or peripheral arterial bypass, cardiac angioplasty or
stent.
- Myocardial infarction
- Severe or unstable angina pectoris
- Peripheral vascular disease, pulmonary embolism or untreated thromboembolic
events, stroke or transient ischemic attack. Note: Patients with recent deep
vein thrombosis (including pulmonary embolism) treated with anticoagulant for
at least 4 weeks and clinically stable are eligible.
- Congestive heart failure class III or IV as defined by the NYHA
16. Concomitant treatment with another experimental treatment or participation in
another clinical trial.