Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Trial on NIraparib-TSR-042 (Dostarlimab) vs Physician's Choice CHEmotherapy in Recurrent, Ovarian, Fallopian Tube or Primary Peritoneal Cancer Patients Not Candidate for Platinum Retreatment (NItCHE-MITO33)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04679064
Recruitment Status : Recruiting
First Posted : December 22, 2020
Last Update Posted : December 22, 2020
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Brief Summary:
Randomized phase 3 trial evaluating niraparib plus dostarlimab vs chemotherapy at physician's choice in the treatment of recurrent ovarian, fallopian tube or primary peritoneal cancer patients for which platinum is not an option

Condition or disease Intervention/treatment Phase
Ovarian Cancer Drug: Niraparib Drug: Dostarlimab Drug: Pegylated liposomal doxorubicin Drug: Paclitaxel Drug: Gemcitabine Drug: Topotecan Drug: Bevacizumab Phase 3

Detailed Description:

Randomized phase 3 trial evaluating niraparib plus dostarlimab vs chemotherapy at physician's choice in the treatment of recurrent ovarian, fallopian tube or primary peritoneal cancer patients for which platinum is not an option.

The patients must have received no more than 2 previous chemotherapy lines. Stratification factors will include HRD status, previous treatment with parp and anti PD-1/PDL-1 inhibitors, Bevacizumab treatment and PDL1 expression.

Patients will continue to receive niraparib until disease progression (determined using RECIST v.1.1 criteria and clinical criteria), unacceptable toxicity, death, withdrawal of consent, or lost to follow-up, whichever comes first. Patients will continue to receive dostarlimab for a maximum of 2 years, or until disease progression (determined using RECIST v1.1 criteria and clinical criteria), unacceptable toxicity, death, withdrawal of consent, lost to follow-up, whichever may come first. Dose interruption and/or reduction may be implemented at any time for any grade toxicity considered intolerable by the patient.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 427 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Phase III Trial on NIraparib-TSR-042 (Dostarlimab) vs Physician's Choice CHEmotherapy in Recurrent, Ovarian, Fallopian Tube or Primary Peritoneal Cancer Patients Not Candidate for Platinum Retreatment: NItCHE Trial (MITO 33)
Actual Study Start Date : December 1, 2020
Estimated Primary Completion Date : January 1, 2025
Estimated Study Completion Date : January 1, 2025


Arm Intervention/treatment
Active Comparator: Phisician's choice of standard chemotherapy

Chemotherapy at physician's choice between Pegylated Liposomal Doxorubicin 40 mg/mq iv q 28 Weekly Paclitaxel 80 mg/mq d 1,8,15 q 28 Gemcitabine 1000 mg/mq d 1,8,15 q 28 Topotecan 1.25 mg/mq day 1-5 q 21

+/- Bevacizumab at defined scehedule

Drug: Pegylated liposomal doxorubicin
Chemotherapy drug

Drug: Paclitaxel
Chemotherapy drug

Drug: Gemcitabine
Chemotherapy drug

Drug: Topotecan
Chemotherapy drug

Drug: Bevacizumab
Chemotherapy drug
Other Name: Avastin

Experimental: Niraparib+Dostarlimab
Dostarlimab 500 mg q 3W for the fist 4 cycles, 1000 mg q 6W thereafter + Niraparib 300 mg or 200 mg if platelet count <150,000 /μL and/or body weight <77kg QD po q 28
Drug: Niraparib
PARP-inihibitor
Other Name: Zejula

Drug: Dostarlimab
PD-1 inihibitor
Other Name: TSR-042




Primary Outcome Measures :
  1. Overall Survival [ Time Frame: 4 years ]
    The length of time from tfrom the date of randomization to the date of death by any cause


Secondary Outcome Measures :
  1. Progression free survival [ Time Frame: 4 years ]
    the length of time from the date of randomization to the earlier date of assessment of progression or death by any cause in the absence of progression.

  2. Time to first subsequent therapy [ Time Frame: 4 years ]
    The length of the time interval from the date of randomization to earliest date of fist subsequent therapy or death

  3. Response rate [ Time Frame: 4 years ]
    the percentage of patients with CR or PR, as assessed by RECIST (Response Evaluation Criteria on Solid Tumor) v.1.1 criteria evaluated by the investigator.

  4. Adverse events [ Time Frame: 4 years ]
    Safety and tolerability of patients receiving chemotherapy or dostarlimab plus niraparib evaluated according to CTCAE vers 5.0.

  5. Patient-reported outcomes for physical well-being [ Time Frame: 4 years ]
    quality of life of patients, in terms of physical well-being, evaluated using EORTC (European Organization for Research and Treatment of Cancer) QLQ C30 (Quality of life Questionnaires C30)

  6. Patient-reported outcomes for physical well-being [ Time Frame: 4 years ]
    quality of life of patients, in terms of physical well-being, evaluated using EORTC (European Organization for Research and Treatment of Cancer) QLQ OV28 (Quality of life Questionnaires OV28)

  7. Patient-reported outcomes for physical well-being [ Time Frame: 4 years ]
    quality of life of patients, in terms of physical well-being, evaluated using EQ-5DL (EURO-QOL)

  8. Patient-reported outcomes for social/family well-being [ Time Frame: 4 years ]
    quality of life of patients, in terms of social/family well-being, evaluated using EORTC (European Organization for Research and Treatment of Cancer) QLQ C30 (Quality of life Questionnaires C30)

  9. Patient-reported outcomes for social/family well-being [ Time Frame: 4 years ]
    quality of life of patients, in terms of social/family well-being, evaluated using EORTC (European Organization for Research and Treatment of Cancer) QLQ OV28 (Quality of life Questionnaires OV28)

  10. Patient-reported outcomes for social/family well-being [ Time Frame: 4 years ]
    quality of life of patients, in terms of social/family well-being, evaluated using EORTC (European Organization for Research and Treatment of Cancer) EQ-5DL (EURO-QOL)

  11. Patient-reported outcomes for emotional well-being [ Time Frame: 4 years ]
    quality of life of patients, in terms of emotional well-being, evaluated using EORTC (European Organization for Research and Treatment of Cancer) QLQ C30 (Quality of life Questionnaires C30)

  12. Patient-reported outcomes for emotional well-being [ Time Frame: 4 years ]
    quality of life of patients, in terms of emotional well-being, evaluated using EORTC (European Organization for Research and Treatment of Cancer) QLQ OV28 (Quality of life Questionnaires OV28)

  13. Patient-reported outcomes for emotional well-being [ Time Frame: 4 years ]
    quality of life of patients, in terms of emotional well-being, evaluated using EORTC (European Organization for Research and Treatment of Cancer) EQ-5DL (EURO-QOL)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Participant must have recurrent ovarian, Fallopian tube or primary peritoneal cancer not candidate for platinum retreatment; and in particular

    • platinum resistant patients (platinum-free interval 1-6 months from last dose of platinum)
    • patients for which platinum is contraindicated because of previous allergic reactions or residual toxicity (i.e nephrotoxicity or neurotoxicity)
    • patients not able( in physician's opinion) to receive further platinum or not willing (in patients' opinion) to receive further platinum
  2. Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
  3. Participants must have measurable disease or evaluable based on RECIST 1.1 (patients with only CA 125 increase without evidence of disease are not included).
  4. Participant must be ≥ 18 years of age
  5. Participant must have adequate organ function
  6. Participant receiving corticosteroids may continue as long as their dose is stable for least 4 weeks prior to initiating protocol therapy.
  7. Participant must agree to not donate blood during the study or for 90 days after the last dose of study treatment.
  8. Participants must agree to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1.

    Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen.

  9. Female participant has a negative urine or serum pregnancy test within 7 days prior to taking study treatment if of childbearing potential and agrees to abstain from activities that could result in pregnancy from screening through 180 days after the last dose of study treatment, or is of nonchildbearing potential.
  10. Participant must agree to not breastfeed during the study or for 180 days after the last dose of study treatment.
  11. Participant must be able to understand the study procedures and agree to participate in the study by providing written informed consent

Exclusion Criteria:

  1. Participant must not be simultaneously enrolled in any interventional clinical trial
  2. Participants have received >2 previous CHT lines (previous treatment with parp inhibitors and/or anti check point inhibitors is allowed providing that at least 6 months from last treatment are intercurred)
  3. Participant must not have had major surgery ≤ 3 weeks prior to initiating protocol therapy and participant must have recovered from any surgical effects.
  4. Participant must not have received investigational therapy ≤ 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is shorter, prior initiating protocol therapy.
  5. Participant has had radiation therapy encompassing >20% of the bone marrow within 2 weeks; or any radiation therapy within 1 week prior to Day 1 of protocol therapy.
  6. Participant must not have a known hypersensitivity to niraparib and dostarlimab components or excipients.
  7. Participant must not have received a transfusion (platelets or red blood cells) ≤ 4 weeks prior to initiating protocol therapy.
  8. Participant must not have received colony-stimulating factors (eg, granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor, or recombinant erythropoietin) within 4 weeks prior initiating protocol therapy.
  9. Participant has had any known Grade 3 or 4 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted > 4 weeks and was related to the most recent treatment.
  10. Participant must not have any known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)
  11. Participant must not have a serious, uncontrolled medical disorder, nonmalignant systemic disease, or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 90 days) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent
  12. Participant must not have had diagnosis, detection, or treatment of another type of cancer ≤ 3 years prior to initiating protocol therapy (except basal or squamous cell carcinoma of the skin and cervical cancer that has been definitively treated)
  13. Participant must not have known, symptomatic brain or leptomeningeal metastases
  14. Patient experienced ≥ Grade 3 immune-related AE with prior immunotherapy, with the exception of non-clinically significant lab abnormalities.
  15. Participant has a diagnosis of immunodeficiency or has received systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to initiating protocol therapy.
  16. Participant has a known history of human immunodeficiency virus (type 1 or 2 antibodies).
  17. Participant has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [qualitative] is detected).
  18. Participant has an active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  19. Participant must not have a history of interstitial lung disease.
  20. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  21. Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines are live attenuated vaccines, and are not allowed.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04679064


Contacts
Layout table for location contacts
Contact: Domenica Lorusso, MD 0630158545 ext 0630158545 domenica.lorusso@policlinicogemelli.it
Contact: Serena Giolitto, MSc 0630158545 ext 0630158545 serena.giolitto@policlinicogemelli.it

Locations
Layout table for location information
Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS Recruiting
Rome, Italy, 00168
Contact: Domenica Lorusso, MD    0630158545 ext 0630158545    domenica.lorusso@policlinicogemelli.it   
Contact: Serena Giolitto, MSc    0630158545 ext 0630158545    serena.giolitto@policlinicogemelli.it   
Sponsors and Collaborators
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
GlaxoSmithKline
Layout table for additonal information
Responsible Party: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
ClinicalTrials.gov Identifier: NCT04679064    
Other Study ID Numbers: 3392
First Posted: December 22, 2020    Key Record Dates
Last Update Posted: December 22, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Gemcitabine
Paclitaxel
Bevacizumab
Doxorubicin
Liposomal doxorubicin
Topotecan
Niraparib
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Topoisomerase I Inhibitors