Informations générales (source: ClinicalTrials.gov)
Randomized Phase III Trial in MMR Deficient Endometrial Cancer Patients Comparing Chemotherapy Alone Versus Dostarlimab in First Line Advanced/Metastatic Setting (DOMENICA)
Interventional
Phase 3
ARCAGY/ GINECO GROUP (Voir sur ClinicalTrials)
avril 2022
octobre 2029
24 août 2024
Phase 3, randomized, multicentre study to evaluate the efficacy and safety of dostarlimab
versus carboplatin-paclitaxel in patients with MMR deficient relapse or advanced
endometrial cancer.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT CURIE | 04/09/2024 13:49:41 | Contact (sur clinicalTrials) | |||
| 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 | Contact (sur clinicalTrials) | ||||
| AP-HP - Hôpital Europeen Georges Pompidou | Contact (sur clinicalTrials) | ||||
| CLCC INSTITUT GUSTAVE ROUSSY | 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 | |||||
| APHM - Hôpital de la Timone - 13005 - Marseille - France | Contact (sur clinicalTrials) | ||||
| AP-HP Hôpital Pitié-Salpêtrière - 75013 - Paris - France | Contact (sur clinicalTrials) | ||||
| Centre Antoine Lacassagne - 06100 - Nice - France | Contact (sur clinicalTrials) | ||||
| Centre Azuréen de Cancérologie - 06250 - Mougins - France | Contact (sur clinicalTrials) | ||||
| Centre CARIO - HPCA - 22190 - Plérin - France | Contact (sur clinicalTrials) | ||||
| Centre Eugène Marquis - 35042 - Rennes - France | Contact (sur clinicalTrials) | ||||
| Centre François Baclesse - 14000 - Caen - France | Contact (sur clinicalTrials) | ||||
| Centre Georges François Leclerc - 21000 - Dijon - France | Contact (sur clinicalTrials) | ||||
| Centre Henri Becquerel - 76038 - Rouen - France | Contact (sur clinicalTrials) | ||||
| Centre Hospitalier d'Auxerre - 89011 - Auxerre - France | Contact (sur clinicalTrials) | ||||
| Centre Hospitalier Général de Pau - 64046 - Pau - France | Contact (sur clinicalTrials) | ||||
| Centre Hospitalier Intercommunal de Créteil - 21079 - Créteil - France | Contact (sur clinicalTrials) | ||||
| Centre Hospitalier Lyon Sud - 69310 - Lyon - France | Contact (sur clinicalTrials) | ||||
| Centre Hospitalier Régional - Orléans - France | Contact (sur clinicalTrials) | ||||
| Centre Hospitalier William Morey - 71100 - Chalon-sur-Saône - France | Contact (sur clinicalTrials) | ||||
| Centre Jean Perrin - 63000 - Clermont-Ferrand - France | Contact (sur clinicalTrials) | ||||
| Centre Léon Bérard - 69373 - Lyon - France | Contact (sur clinicalTrials) | ||||
| Centre Oscar Lambret - 59020 - Lille - France | Contact (sur clinicalTrials) | ||||
| CHI de Cornouaille - Quimper - France | Contact (sur clinicalTrials) | ||||
| CHRU Jean Minjoz - 25000 - Besançon - France | Contact (sur clinicalTrials) | ||||
| CHU Brest - Brest - France | Contact (sur clinicalTrials) | ||||
| CHU Bretonneau - Tours - France | Contact (sur clinicalTrials) | ||||
| CHU de Dijon - 21079 - Dijon - France | Contact (sur clinicalTrials) | ||||
| CHU de Poitiers - Hôpital de la Milétrie - 86021 - Poitiers - France | Contact (sur clinicalTrials) | ||||
| CHU Saint-Etienne - Pôle de Cancérologie - 42055 - Saint-Étienne - France | Contact (sur clinicalTrials) | ||||
| Clinique Victor Hugo - 72000 - Le Mans - France | Contact (sur clinicalTrials) | ||||
| Groupe Hospitalier Diaconesses-Croix Saint-Simon - 75020 - Paris - France | Contact (sur clinicalTrials) | ||||
| Hôpital de Mont-de-Marsan - Mont de Marsan - France | Contact (sur clinicalTrials) | ||||
| Hôpital Privé du Confluent S.A.S. - 44000 - Nantes - France | Contact (sur clinicalTrials) | ||||
| Hôpital Saint-Joseph - 13285 - Marseille - France | Contact (sur clinicalTrials) | ||||
| ICL - Centre Alexis Vautrin - 54511 - Vandœuvre-lès-Nancy - France | Contact (sur clinicalTrials) | ||||
| ICM Val d'Aurelle - 34298 - Montpellier - France | Contact (sur clinicalTrials) | ||||
| ICO - Centre René Gauducheau - 44805 - Saint-Herblain - France | Contact (sur clinicalTrials) | ||||
| ICO Paul Papin - 49055 - Angers - France | Contact (sur clinicalTrials) | ||||
| Institut Bergonié - 33076 - Bordeaux - France | Contact (sur clinicalTrials) | ||||
| Institut Claudius Régaud - 31059 - Toulouse - France | Contact (sur clinicalTrials) | ||||
| Institut de Cancérologie de Strasbourg Europe - ICANS - 67200 - Strasbourg - France | Contact (sur clinicalTrials) | ||||
| Institut de cancérologie du gard - 30029 - Nîmes - France | Contact (sur clinicalTrials) | ||||
| Institut Jean Godinot - Reims - France | Contact (sur clinicalTrials) | ||||
| Institut Mutualiste Montsouris - Paris - France | Contact (sur clinicalTrials) | ||||
| Institut Paoli Calmettes - 13273 - Marseille - France | Contact (sur clinicalTrials) | ||||
| Institut Sainte Catherine - Avignon - France | Contact (sur clinicalTrials) | ||||
| Médipôle de NANCY SAS - Nancy - France | Contact (sur clinicalTrials) | ||||
| ROC 37 - Chambray-lès-Tours - France | Contact (sur clinicalTrials) | ||||
Critères
Femme
Inclusion Criteria:
- Patients must fulfil all the following criteria:
1. Female patient is at least 18 years of age,
2. Patient has signed the Informed Consent (ICF) and is able to comply with
protocol requirements.
3. Patient with histologically proven endometrial adenocarcinoma with recurrent or
advanced disease.
4. Patient with an Eastern Cooperative Oncology Group (ECOG) performance status
score of 0 or 1.
5. Patient must have primary Stage IIIA to C2 or Stage IV disease or first
recurrent endometrial cancer (see International Federation of Gynecology and
Obstetrics staging FIGO Staging 18.1) without curative treatment by radiation
therapy or surgery alone or in combination, and meet at least one of the
following situations:
1. Patient has patient has primary Stage IIIA-IIIC1 with no amenable curative
intent surgery or radiation.
2. Patient has first recurrent disease and is chemotherapy naïve for this 1st
recurrence or metastatic setting.
3. Patient has recurrent disease and is chemotherapy naïve for recurrence or
advanced /metastatic setting.
4. Patient may have received prior irradiation for advanced endometrial
cancer with or without radio-sensitizing chemotherapy if > 3 weeks before
the start of the study
6. Patient with evaluable disease (measurable and not measurable disease)
according to RECIST 1.1
7. Patient may have received prior neo-adjuvant/adjuvant systemic chemotherapy for
the primary cancer and had a recurrence ≥ 6 months after completing treatment
(first recurrence only).
8. All histologic subtypes of endometrial adenocarcinoma could be included if
MMRd/MSI-H
9. MMRd/MSI-H tumor (first diagnosed by routine local IHC performed either on
primitive tumour tissue or on relapse/metastatic tumour sample) is mandatory
for inclusion. A central confirmation will be done before inclusion; in case of
ambiguous result of central IHC (lack of positive internal control,
heterogeneous loss of MMR protein expression), MSI-H status will be assessed by
PCR/NGS
10. Availability of 1 block for MMR/MSI status centralized confirmation for IHC or
PCR/ NGS
11. . Patient could have been previously treated with hormone therapy, for the
metastatic/advanced disease 12) Patient may have received pelvic and
lombo-aortic external beam +/- vaginal brachytherapy
13. Patient has adequate organ function, defined as follows:
a) Absolute neutrophil count ≥ 1,500 cells/μL b) Platelets ≥ 100,000 cells/μL c)
Haemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L d) Serum creatinine ≤ 1.5× upper limit of
normal (ULN) or calculated creatinine clearance ≥ 50 mL/min using the
Cockcroft-Gault equation for patients with creatinine levels > 1.5× institutional
ULN e) Total bilirubin ≤ 1.5× ULN (≤ 2.0 x ULN in patients with known Gilbert's
syndrome) or direct bilirubin ≤ 1× ULN f) Aspartate aminotransferase (AST) and
alanine aminotransferase (ALT) ≤ 2.5× ULN unless liver metastases are present, in
which case they must be ≤ 5× ULN g) International normalized ratio or prothrombin
time (PT) ≤1.5× ULN and activated partial thromboplastin time ≤1.5× ULN. Patients
receiving anticoagulant therapy must have a PT or partial thromboplastin within the
therapeutic range of intended use of anticoagulants.
14. Patient must have a negative serum pregnancy test within 72 hours of the first
dose of study medication, unless they are of nonchildbearing potential.
Nonchildbearing potential is defined as follows:
1. Patient is ≥ 45 years of age and has not had menses for > 1 year.
2. A follicle-stimulating hormone value in the postmenopausal range upon screening
evaluation if amenorrhoeic for < 2 years without a hysterectomy and
oophorectomy.
3. Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation:
- Documented hysterectomy or oophorectomy must be confirmed with medical records of
the actual procedure or confirmed by an ultrasound, MRI, or CT scan.
- Tubal ligation must be confirmed with medical records of the actual procedure;
otherwise, the patient must fulfil the criteria in Inclusion Criterion 14.
- Information must be captured appropriately within the site's source documents. 15.
Patient of childbearing potential must agree to use a highly effective method of
contraception (section 18.9) with their partners starting from time of consent
through 150 days after the last dose of study treatment. Note: Abstinence is
acceptable if this is the established and preferred contraception for the patient
(Information must be captured appropriately within the site's source documents).
- Patients must fulfil all the following criteria:
1. Female patient is at least 18 years of age,
2. Patient has signed the Informed Consent (ICF) and is able to comply with
protocol requirements.
3. Patient with histologically proven endometrial adenocarcinoma with recurrent or
advanced disease.
4. Patient with an Eastern Cooperative Oncology Group (ECOG) performance status
score of 0 or 1.
5. Patient must have primary Stage IIIA to C2 or Stage IV disease or first
recurrent endometrial cancer (see International Federation of Gynecology and
Obstetrics staging FIGO Staging 18.1) without curative treatment by radiation
therapy or surgery alone or in combination, and meet at least one of the
following situations:
1. Patient has patient has primary Stage IIIA-IIIC1 with no amenable curative
intent surgery or radiation.
2. Patient has first recurrent disease and is chemotherapy naïve for this 1st
recurrence or metastatic setting.
3. Patient has recurrent disease and is chemotherapy naïve for recurrence or
advanced /metastatic setting.
4. Patient may have received prior irradiation for advanced endometrial
cancer with or without radio-sensitizing chemotherapy if > 3 weeks before
the start of the study
6. Patient with evaluable disease (measurable and not measurable disease)
according to RECIST 1.1
7. Patient may have received prior neo-adjuvant/adjuvant systemic chemotherapy for
the primary cancer and had a recurrence ≥ 6 months after completing treatment
(first recurrence only).
8. All histologic subtypes of endometrial adenocarcinoma could be included if
MMRd/MSI-H
9. MMRd/MSI-H tumor (first diagnosed by routine local IHC performed either on
primitive tumour tissue or on relapse/metastatic tumour sample) is mandatory
for inclusion. A central confirmation will be done before inclusion; in case of
ambiguous result of central IHC (lack of positive internal control,
heterogeneous loss of MMR protein expression), MSI-H status will be assessed by
PCR/NGS
10. Availability of 1 block for MMR/MSI status centralized confirmation for IHC or
PCR/ NGS
11. . Patient could have been previously treated with hormone therapy, for the
metastatic/advanced disease 12) Patient may have received pelvic and
lombo-aortic external beam +/- vaginal brachytherapy
13. Patient has adequate organ function, defined as follows:
a) Absolute neutrophil count ≥ 1,500 cells/μL b) Platelets ≥ 100,000 cells/μL c)
Haemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L d) Serum creatinine ≤ 1.5× upper limit of
normal (ULN) or calculated creatinine clearance ≥ 50 mL/min using the
Cockcroft-Gault equation for patients with creatinine levels > 1.5× institutional
ULN e) Total bilirubin ≤ 1.5× ULN (≤ 2.0 x ULN in patients with known Gilbert's
syndrome) or direct bilirubin ≤ 1× ULN f) Aspartate aminotransferase (AST) and
alanine aminotransferase (ALT) ≤ 2.5× ULN unless liver metastases are present, in
which case they must be ≤ 5× ULN g) International normalized ratio or prothrombin
time (PT) ≤1.5× ULN and activated partial thromboplastin time ≤1.5× ULN. Patients
receiving anticoagulant therapy must have a PT or partial thromboplastin within the
therapeutic range of intended use of anticoagulants.
14. Patient must have a negative serum pregnancy test within 72 hours of the first
dose of study medication, unless they are of nonchildbearing potential.
Nonchildbearing potential is defined as follows:
1. Patient is ≥ 45 years of age and has not had menses for > 1 year.
2. A follicle-stimulating hormone value in the postmenopausal range upon screening
evaluation if amenorrhoeic for < 2 years without a hysterectomy and
oophorectomy.
3. Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation:
- Documented hysterectomy or oophorectomy must be confirmed with medical records of
the actual procedure or confirmed by an ultrasound, MRI, or CT scan.
- Tubal ligation must be confirmed with medical records of the actual procedure;
otherwise, the patient must fulfil the criteria in Inclusion Criterion 14.
- Information must be captured appropriately within the site's source documents. 15.
Patient of childbearing potential must agree to use a highly effective method of
contraception (section 18.9) with their partners starting from time of consent
through 150 days after the last dose of study treatment. Note: Abstinence is
acceptable if this is the established and preferred contraception for the patient
(Information must be captured appropriately within the site's source documents).
- Patients are to be excluded from the study if they meet any of the following
criteria:
1. Patient has received neoadjuvant/adjuvant systemic chemotherapy for primary
Stage III or IV disease and has had a recurrence or PD within 6 months of
completing this chemotherapy treatment prior to entering the study.
Note: Low-dose cisplatin given as a radiation sensitizer or hormonal therapies
do not exclude patients from study participation.
2. Patient has had > 1 recurrence of endometrial cancer, treated with
chemotherapy. Surgery of the recurrence is allowed.
3. Patient previously treated with systemic chemotherapy for non-curable advanced
disease or metastatic disease
4. Patient has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2
agent.
5. Patient has received prior anticancer therapy for (advanced or metastatic
disease (targeted therapies, hormonal therapy, radiotherapy) within 21 days or
< 5 times the half-life of the most recent therapy prior to Study Day 1,
whichever is shorter Note: Palliative radiation therapy to a small field ≥ 1
week prior to Day 1 of study treatment may be allowed.
6. Patient with contraindication to chemotherapy or checkpoint inhibitor
treatments
7. Patient has a concomitant malignancy, or patient has a prior non-endometrial
invasive malignancy who has been disease-free for < 3 years or who received any
active treatment in the last 3 years for that malignancy. Non-melanoma skin
cancer is allowed.
8. Patient has known uncontrolled central nervous system metastases,
carcinomatosis meningitis, or both. Note: Patients with previously treated
brain metastases may participate provided they are stable (without evidence of
disease progression by imaging [using the identical imaging modality for each
assessment, either MRI or CT scan] for at least 4 weeks prior to the first dose
of study treatment and any neurologic symptoms have returned to baseline), have
no evidence of new or enlarging brain metastases, and have not been using
steroids for at least 7 days prior to study treatment. Carcinomatous meningitis
precludes a patient from study participation regardless of clinical stability.
9. Patient has a known history of human immunodeficiency virus (HIV; HIV 1 or 2
antibodies).
10. Patient has known active viral infection of hepatitis B (eg, hepatitis B
surface antigen reactive) or hepatitis C (eg, hepatitis C virus ribonucleic
acid [qualitative] detection).
11. Patient has an active autoimmune disease that has required systemic treatment
in the past 2 years. Replacement therapy is not considered a form of systemic
therapy (eg, thyroid hormone or insulin).
12. Patient has a diagnosis of immunodeficiency or is receiving systemic steroid
therapy or any other form of systemic immunosuppressive therapy within 7 days
prior to the first dose of study treatment.
13. Patient has not recovered (ie, to Grade ≤ 1 or to baseline) from cytotoxic
therapy-induced adverse events (AEs).
Note: Patients with Grade ≤ 2 neuropathy, Grade ≤ 2 alopecia, or Grade ≤ 2
fatigue are an exception to this criterion and may qualify for the study.
14. Patient has not recovered adequately from AEs or complications from any major
surgery prior to starting therapy.
15. Patient has a known hypersensitivity to carboplatin, paclitaxel, or dostarlimab
components or excipients.
16. Patient is currently participating and receiving study treatment or has
participated in a study of an investigational agent and received study
treatment or used an investigational device within 4 weeks of the first dose of
treatment.
17. Patient is considered a poor medical risk due to a serious, uncontrolled
medical disorder, non-malignant systemic disease, or active infection requiring
systemic therapy. Specific examples include, but are not limited to, active,
non-infectious pneumonitis; uncontrolled ventricular arrhythmia; recent (within
90 days) myocardial infarction; uncontrolled major seizure disorder; unstable
spinal cord compression; superior vena cava syndrome; or any psychiatric or
substance abuse disorders that would interfere with cooperation with the
requirements of the study (including obtaining informed consent).
18. Use of any of the following immunomodulatory agents within 30 days prior to the
first dose of study drug:
- Systemic corticosteroids (at dose higher than 10 mg/day equivalent
prednisone); if systemic corticoid use at higher dose than 10 mg/day,
corticoid must be stopped at least 7 days before study treatment start
- Interferons
- Interleukins
- Live vaccine Note: Examples of live vaccines include, but are not limited
to, the following: measles, mumps, rubella, varicella/zoster, yellow
fever, rabies, BCG, and typhoid vaccine. Seasonal influenza vaccines for
injection are generally killed virus vaccines and are allowed as other
killed vaccines, if done at least 2 weeks prior the first dose of study
drug; however, intranasal influenza vaccines (eg, FluMist®) are live
attenuated vaccines and are not allowed.
19. Patient is pregnant or breastfeeding or is expecting to conceive children
within the projected duration of the study, starting with the screening visit
through 180 days after the last dose of study treatment, or lactating woman.
20. Patients who had an allogenic tissue/solid organ transplant