Endometrial Cancer Patientes MMR Deficient Comparing Chemotherapy vs Dostarlimab in First Line (DOMENICA)

• ClinicalTrials.gov Identifier: NCT05201547
• Recruitment Status: Recruiting
• First Posted: January 21, 2022
• Last Update Posted: February 29, 2024
• Sponsor: ARCAGY/ GINECO GROUP
• Collaborator: GlaxoSmithKline
• Information provided by (Responsible Party): ARCAGY/ GINECO GROUP

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Endometrial Cancer	Drug: Carboplatin-Paclitaxel; Drug: Dostarlimab	Phase 3

Detailed Description:

Phase III, randomized, open label, multi-centre study.

Randomization on a 1:1 ratio, stratification performed according to:

• Prior adjuvant chemotherapy (yes or no)
• Prior pelvic radiotherapy (yes or no)
• Disease status: newly diagnosed advanced / metastatic disease versus relapse

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 260 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized Phase III Trial in MMR Deficient Endometrial Cancer Patients Comparing Chemotherapy Alone Versus Dostarlimab in First Line Advanced/Metastatic Setting
• Actual Study Start Date: April 15, 2022
• Estimated Primary Completion Date: April 2026
• Estimated Study Completion Date: October 2029

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm A: Dostarlimab 500 mg, every 3 weeks, 4 cycles and then 1000 mg every 6 weeks	Drug: Dostarlimab; Dostarlimab will be administered through a 30-minute infusion at a dose of 500 mg Q3W from Cycle 1 through Cycle 4 and at a dose of 1,000 mg Q6W thereafter, beginning at Cycle 5 Day 1 up to a maximum of 2 years.
Experimental: Arm B: Carboplatin AUC 5 or 6 plus Paclitaxel 175 mg/m2, every 3 weeks, 6 cycles.	Drug: Carboplatin-Paclitaxel; Chemotherapy will be administered by intravenous infusion. Carboplatin AUC 5-6 + Pacltaxel 175 mg/m² every 3 weeks. Total duration of treatment: 6 cycles

Outcome Measures

Primary Outcome Measures :

1. Progression Free Survival (PFS) [ Time Frame: from the date of randomization until objective tumor progression based on RECIST 1.1, or death due to any cause, whichever occurs first assessed up to 5 years. ]
   Defined as the time from the date of randomization until objective tumor progression based on RECIST 1.1, by BICR (Blinded Independent Central Review), or death due to any cause, whichever occurs first. Patients alive and free of progression will be censored at the last disease assessment date.

Secondary Outcome Measures :

1. Overall Survival (OS) (key secondary endpoint) [ Time Frame: from the date of randomization until death due to any cause, assessed up to 5 years ]
   Measured as the time from the date of randomization to the date of death due to any cause. Patients alive at the cut-off date will be censored at the last date they are known to be alive.
2. Progression Free Survival 2 (PFS2) [ Time Frame: from the date of randomization until second objective tumor progression based on RECIST 1.1, or death due to any cause, whichever occurs first assessed up to 5 years ]
   Defined by the time from initial randomization to the second objective disease progression (ie, after the first subsequent therapy) as assessed by the investigator or death due to any cause, whoever occurs first. Patients alive and free of second progression (including patients without any progression), will be censored at the last disease assessment date.
3. Quality Of Life evaluation based on Quality of Life Questionnaire EQ5D5L (The 5-level EQ-5D version) [ Time Frame: through study completion, an average of 5 years ]
   The EQ-5D-5L essentially consists of 2 pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems
4. To assess the effects of Dostarlimab on Health related quality of Life (QoL) based on EORTC QLQ C30 (Quality of Life questionnaire-core 30) [ Time Frame: Defined as the Global Health Status score from the EORTC QLQ C30 at 18 weeks, assessed up to 5 years ]
   Health related quality of life of the patient. For all scales a high score is equivalent to worse or more problems. Range is the difference between the maximum and minimum possible value of the raw score. All items are scored from1 to 4, giving a range=3. For each scale, calculate the raw score by the addition of item responses divided by the number of items. Then a linear transformation is used to standardise the raw score, so that scores range from 0 to 100. Score= (raw score-1)/rangex100
5. To assess the quantity of peripheral neuropathy event induced by chemotherapy based on EORTC QLQ-CIPN 20 (Quality of Life questionnaire-Chemotherapy induced peripheral neuropathy 20) [ Time Frame: Defined as the Global Health Status score from the EORTC QLQ-CIP20 at 18 weeks, assessed up to 5 years ]
   Chemotherapy induced peripheral neuropathy assessed by QLQ-CIPN20 at 18 weeks for each problems or symptoms there are a scales with a high score which is equivalent to worse or more. All items are scored from1 to 4, giving a range=3. 1 = Not at all and 4 = Very much. For each scale, calculate the raw score by the addition of item responses divided by the number of items.
6. To assess the effects of treatment on health-related quality of life (HRQoL) as measure by determining time to deterioration in Quality of life, based EORTC QLQ-EN24 (Quality of Life Questionnaire - Endometrial Cancer Module) [ Time Frame: Defined as the Global Health Status score from the EORTC QLQ-EN24 at 18 weeks, assessed up to 5 years ]
   To assess disease and treatment specific aspects of the quality of life of patients with endometrial cancer. A high score for the functional scales represents a high level of functioning, while a high score for the symptom scales represents a high level of symptoms or problems. Symptoms related to sexual/vaginal problems (EMSXV including item 51-53) are optional.
7. To assess the status of health for patients with endometrial cancer based on EUROQOL EQ-5D (Descriptive system) [ Time Frame: Defined as the Global Health Status score from the EUROQOL EQ-5D at 18 weeks, assessed up to 5 years ]
   Deterioration and impact on patients' life of endometrial cancer assessed by the questionnaire EUROQOL EQ-5D
8. Best Objective Response Rate (ORR) [ Time Frame: from the date of randomization until best objective response based on RECIST 1.1, assessed up to 5 years ]
   Defined as the proportion of patients with confirmed complete or partial response as per RECIST 1.1
9. Disease Control Rate (DCR) [ Time Frame: from the date of randomization until response or stable disease per RECIST 1.1, assessed up to 5 years ]
   Defined as the proportion of participants who have achieved confirmed CR or PR or have demonstrated SD for at least 24 weeks; per RECIST 1.1.
10. Duration of Response Rate (DoR) [ Time Frame: from the time of initial response until documented tumor progression ,assessed up to 5 years ]
    Measured from the time of initial response until documented tumor progression.
11. Safety and number of adverse events [ Time Frame: From date of randomization until end of study, assessed up to 6 years ]
    Measured from the time of initial response until documented tumor progression.
12. Tolerability to the treatment [ Time Frame: From date of randomization until end of study, assessed up to 6 years ]
    Assessed by CTCAE v5.0 (by investigators) Assessed by NCI PRO-CTCAE (by patients)
13. Time to first and second Subsequent Treatment [ Time Frame: from the date of randomization to date of event, assessed up to an average of 5 years ]
    Defined as the time from the date of randomization to date of respectively the first and second subsequent anticancer therapy or death.
14. To determine the immunogenicity of dostarlimab [ Time Frame: from randomisation to 12 weeks after end of treatment, assessed at study end ]
    Incidence of ADA against dostarlimab

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

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, and additional block(s) for Translational Research
  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).

Exclusion Criteria:

• 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, 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

Contacts and Locations

Contacts

Contact: Ophélie BACONNET; 01 84 85 20 20; Domenica@arcagy.org

Locations

Australia

Canberra Hospital; Not yet recruiting

Garran, Australia, 2605

Principal Investigator: Alison DAVIS

Calvary Mater Newcastle; Active, not recruiting

Waratah, Australia, 2298

France

ICO Paul Papin; Recruiting

Angers, France, 49055

Principal Investigator: Paule AUGEREAU, MD

Institut Sainte Catherine; Recruiting

Avignon, France

Principal Investigator: Bertrand BILLEMONT, MD.

CHRU Jean Minjoz; Recruiting

Besançon, France, 25000

Principal Investigator: Guillaume MEYNARD, MD

Institut Bergonié; Recruiting

Bordeaux, France, 33076

Principal Investigator: Coriolan LEBRETON, MD

CHU Brest; Recruiting

Brest, France

Principal Investigator: Laura Deiana, MD.

Centre François Baclesse; Recruiting

Caen, France, 14000

Principal Investigator: Florence JOLY, MD

ROC 37; Recruiting

Chambray-lès-Tours, France

Principal Investigator: Pierre COMBE, MD.

Centre Jean Perrin; Recruiting

Clermont-Ferrand, France, 63000

Principal Investigator: Laure VACHER, MD

Centre Hospitalier Intercommunal de Créteil; Active, not recruiting

Créteil, France, 21079

Centre Georges François Leclerc; Recruiting

Dijon, France, 21000

Principal Investigator: Laure FAVIER, MD

CHU de Dijon; Recruiting

Dijon, France, 21079

Principal Investigator: Marie CHAIX, MD

Clinique Victor Hugo; Active, not recruiting

Le Mans, France, 72000

Centre Oscar Lambret; Recruiting

Lille, France, 59020

Principal Investigator: Valérie CHEVALIER-EVAIN, MD

Centre Hospitalier Lyon Sud; Recruiting

Lyon, France, 69310

Principal Investigator: Julien PERON, MD

Centre Léon Bérard; Recruiting

Lyon, France, 69373

Principal Investigator: Isabelle RAY COQUARD, MD

APHM - Hôpital de la Timone; Not yet recruiting

Marseille, France, 13005

Principal Investigator: Marie MEURER, MD

Institut Paoli Calmettes; Recruiting

Marseille, France, 13273

Principal Investigator: Renaud SABATIER, MD

Hôpital Saint-Joseph; Active, not recruiting

Marseille, France, 13285

Hôpital de Mont-de-Marsan; Recruiting

Mont de Marsan, France

Principal Investigator: Lucie VITSE, MD

ICM Val d'Aurelle; Recruiting

Montpellier, France, 34298

Principal Investigator: Michel FABBRO, MD

Centre Azuréen de Cancérologie; Recruiting

Mougins, France, 06250

Principal Investigator: Rémy LARGILLIER, MD

Médipôle de NANCY SAS; Active, not recruiting

Nancy, France

Hôpital Privé du Confluent S.A.S.; Recruiting

Nantes, France, 44000

Principal Investigator: Alain Lortholary, MD

Centre Antoine Lacassagne; Recruiting

Nice, France, 06100

Principal Investigator: Philippe FOLLANA, MD

Institut de cancérologie du gard; Active, not recruiting

Nîmes, France, 30029

Centre Hospitalier Régional; Active, not recruiting

Orléans, France

Institut Curie; Recruiting

Paris, France, 75005

Principal Investigator: Mathilde SAINT-GHISLAIN, MD

AP-HP Hôpital Pitié-Salpêtrière; Not yet recruiting

Paris, France, 75013

Principal Investigator: Hervé FOKA TICHOUE

Hôpital Cochin; Recruiting

Paris, France, 75014

Principal Investigator: Jérôme ALEXANDRE, MD

Groupe Hospitalier Diaconesses-Croix Saint-Simon; Recruiting

Paris, France, 75020

Principal Investigator: Antoine ANGELLERGUES, MD

Hôpital Européen Georges Pompidou; Recruiting

Paris, France

Principal Investigator: Nicolas DELANOY, MD

Institut Mutualiste Montsouris; Not yet recruiting

Paris, France

Principal Investigator: Marie-Liesse JOULIA, MD

Centre CARIO - HPCA; Recruiting

Plérin, France, 22190

Principal Investigator: Anne-Claire HARDY-BESSARD, MD

CHU de Poitiers - Hôpital de la Milétrie; Recruiting

Poitiers, France, 86021

Principal Investigator: Patrick BOUCHAERT, MD

CHI de Cornouaille; Active, not recruiting

Quimper, France

Institut Jean Godinot; Recruiting

Reims, France

Principal Investigator: Aude-Marie SAVOYE, MD

Centre Eugène Marquis; Recruiting

Rennes, France, 35042

Principal Investigator: Céline LESCURE, MD

Centre Henri Becquerel; Active, not recruiting

Rouen, France, 76038

ICO - Centre René Gauducheau; Recruiting

Saint-Herblain, France, 44805

Principal Investigator: Jean-Sébastien FRENEL, MD

CHU Saint-Etienne - Pôle de Cancérologie; Recruiting

Saint-Étienne, France, 42055

Principal Investigator: Michele LAMURAGLIA, MD

Institut de Cancérologie de Strasbourg Europe - ICANS; Recruiting

Strasbourg, France, 67200

Principal Investigator: Lauriane EBERST, MD

Institut Claudius Régaud; Recruiting

Toulouse, France, 31059

Principal Investigator: Laurence GLADIEFF, MD

CHU Bretonneau; Recruiting

Tours, France

Principal Investigator: Marie-Agnès BY, MD.

ICL - Centre Alexis Vautrin; Recruiting

Vandœuvre-lès-Nancy, France, 54511

Principal Investigator: Yolanda FERNANDEZ, MD

Institut Gustave Roussy; Recruiting

Villejuif, France, 94805

Principal Investigator: Alexandra Leary, MD

Singapore

National University Hospital (NUH); Not yet recruiting

Singapore, Singapore, 119074

Principal Investigator: Shao Peng DAVID TAN

National Cancer Centre Singapore (NCCS); Not yet recruiting

Singapore, Singapore, 169610

Principal Investigator: Jack Junjie CHAN

Sponsors and Collaborators

ARCAGY/ GINECO GROUP

GlaxoSmithKline

Investigators

• Principal Investigator: Florence JOLY, Pr; Centre François Baclesse

More Information

• Responsible Party: ARCAGY/ GINECO GROUP
• ClinicalTrials.gov Identifier: NCT05201547
• Other Study ID Numbers: GINECO-EN105b
• First Posted: January 21, 2022
• Last Update Posted: February 29, 2024
• Last Verified: December 2023

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by ARCAGY/ GINECO GROUP:

MMR; first line; metastatic; dostarlimab

Additional relevant MeSH terms:

Endometrial Neoplasms; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Paclitaxel; Carboplatin; Dostarlimab; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action