Phase III Randomized Trial of Niraparib and Dostarlimab Versus Physician's Choice Chemotherapy in Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
- Trial ID
- 2024-516649-38-00
- Protocol
- MITO 33
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this randomized phase III trial is to assess **overall survival (OS)** in patients with recurrent ovarian, fallopian tube, or primary peritoneal cancer who are not candidates for platinum retreatment. Overall survival is defined as the time from randomization to the date of death by any cause. This measure is clinically relevant as it directly evaluates the efficacy of the treatment regimen in prolonging life in a patient population with limited therapeutic options.
Participants
The clinical trial involves a study population exclusively comprising **female** participants diagnosed with **recurrent ovarian, fallopian tube, or primary peritoneal cancer**. The age range of the participants is 18 years and older, with no upper age limit specified. Participants are required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. The trial does not include a vulnerable population. Participants must have adequate organ function and measurable disease based on RECIST 1.1 criteria. Lifestyle considerations such as diet, physical activity, or habits are not specified. The sponsor has not provided information regarding the total number of participants in the trial. The selection criteria include the ability to understand study procedures and provide written informed consent. Participants must agree to not donate blood or breastfeed during the study and for a specified period after the last dose of study treatment. The trial population was selected based on specific medical and health criteria, ensuring participants are not candidates for platinum retreatment due to resistance or contraindications. The sponsor has not provided information on the total number of participants in the trial.
Plans and Procedures
The clinical trial is a **randomized**, **phase III** study designed to evaluate the efficacy of **niraparib** and **dostarlimab** compared to physician's choice chemotherapy in patients with recurrent ovarian, fallopian tube, or primary peritoneal cancer who are not candidates for platinum retreatment. The primary objective is to assess overall survival, defined as the time from randomization to the date of death by any cause. The trial is structured as a **double-blind** and **controlled** study, ensuring that neither the participants nor the investigators know which treatment the participants are receiving, thus minimizing bias.
The trial is expected to last until January 31, 2027, with recruitment having started on December 16, 2020. Participants will be involved in the study for a maximum treatment period of 24 months. The study includes several key visits: an initial screening visit to determine eligibility based on inclusion criteria such as having a recurrent form of the specified cancers, an ECOG performance status of ≤ 1, and adequate organ function. Follow-up visits will occur regularly to monitor the participants' health, treatment response, and any adverse effects. The end-of-study visit will conclude the participant's involvement, where final assessments will be conducted.
Participants may be withdrawn from the study early if they experience unacceptable toxicity, disease progression, or if they withdraw consent. Additionally, participants must agree to not donate blood during the study and for 90 days after the last dose of study treatment. Female participants of childbearing potential must have a negative pregnancy test prior to treatment and agree to use effective contraception during the study and for 180 days after the last dose. The study is conducted under strict ethical guidelines, ensuring that all participants provide informed consent and understand the study procedures.
Treatment
The clinical trial involves the administration of several **experimental medications** and comparator treatments. **Paclitaxel** is administered as an intravenous anti-cancer agent with a maximum daily dose of 80 mg/m² and a total dose not exceeding 5760 mg/m² over a 24-week period. The pharmaceutical form is PHF00230MIG, and it is a chemical substance known by synonyms such as Oncogel, ABI-007, and MBT 0206.
**Dostarlimab** is used as an immunotherapy solution for infusion, with a maximum daily dose of 1000 mg and a total dose of up to 16000 mg over 24 weeks. The pharmaceutical form is PHF00230MIG, and it is a protein-based substance, also referred to as WBP-285 and TSR-042.
**Niraparib** is administered orally as an oncological agent, with a maximum daily dose of 300 mg and a total dose of 219000 mg over 24 weeks. The pharmaceutical form is PHF00006MIG, and it is a chemical substance, also known as MK-4827.
**Topotecan** is provided as an intravenous anti-cancer agent, with a maximum daily dose of 1.25 mg/m² and a total dose of 212.5 mg/m² over 24 weeks. The pharmaceutical form is PHF00006MIG, and it is a chemical substance, synonymously referred to as Nogitecan.
**Doxorubicin Hydrochloride** is administered as a concentrate for solution for infusion, with a maximum daily dose of 50 mg/m² and a total dose of 1200 mg/m² over 24 weeks. The pharmaceutical form is PHF00231MIG, and it is a chemical substance without additional synonyms.
**Gemcitabine Hydrochloride** is used as an intravenous anti-cancer agent, with a maximum daily dose of 1000 mg/m² and a total dose of 24000 mg/m² over 24 weeks. The pharmaceutical form is PHF00230MIG, and it is a chemical substance, also known by its chemical name 4-amino-1-[(2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one hydrochloride.
**Bevacizumab** is administered intravenously as an anti-cancer agent, with a maximum daily dose of 15 mg/kg and a total dose of 510 mg/kg over 24 weeks. The pharmaceutical form is PHF00230MIG, and it is a protein-based substance, known by several synonyms including BI 695502, BS-503A, and PF-06439535.
Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed treatment regimens. The trial aims to assess overall survival in patients with recurrent ovarian, fallopian tube, or primary peritoneal cancer who are not candidates for platinum retreatment.
Efficacy
The efficacy of the clinical trial will be assessed primarily through the evaluation of **Overall Survival (OS)**, which is defined as the time from randomization to the date of death by any cause. This endpoint is critical in determining the effectiveness of the treatment regimen being tested. The trial involves a comparison between the combination of **Niraparib** and **Dostarlimab** versus the physician's choice of chemotherapy in patients with recurrent ovarian, fallopian tube, or primary peritoneal cancer who are not candidates for platinum retreatment.
The measurement of OS will be conducted at various timepoints throughout the trial, with data collection continuing until the estimated end date of January 31, 2027. The analysis of OS will involve statistical methods appropriate for survival data, ensuring that the results are robust and reliable. The trial is designed as a randomized phase III study, which provides a high level of evidence regarding the efficacy of the treatment under investigation.
Inclusion and Exclusion Criteria
Inclusion Criteria
- a. 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 the first platinum treatment) - patients for which platinum is contraindicated because of previous allergic reactions or residual toxicity b. Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 c. 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). d. Participant must be ≥ 18 years of age e. Participant must have adequate organ function, defined as follows: • Absolute neutrophil count ≥ 1,500/μL • Platelets ≥ 100,000/μL • Hemoglobin ≥ 9 g/dL • Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 60mL/min using the Cockcroft-Gault equation • Total bilirubin ≤ 1.5 x ULN (≤2.0 in patients with known Gilberts syndrome) OR direct bilirubin ≤ 1 x ULN • Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x ULN unless liver metastases are present, in which case they must be ≤ 5 x ULN • International normalized ratio (INR) or prothrombin time (PT) ≤1.5× ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin (PTT) is within therapeutic range of intended use of anticoagulants. Activated partial thromboplastin time (aPTT) ≤1.5× ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants f. Pre-existing hypertension should be adequately controlled before starting niraparib treatment g. Participant must agree to not donate blood during the study or for 90 days after the last dose of study treatment. h. 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 prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided may submit an archived specimen. i. 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. Nonchildbearing potential is defined as follows: • ≥45 years of age and has not had menses for >1 year and has a high follicle-stimulating hormone (FSH) level in the postmenopausal ranges confirmed by two FSH measurements • Patients who have been amenorrhoeic for <2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation • 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. Tubal ligation must be confirmed with medical records of the actual procedure, otherwise the patient must be willing to use 2 adequate barrier methods throughout the study, starting with the screening visit through 180 days after the last dose of study treatment. See Section 4.4 for a list of acceptable birth control methods. Information must be captured appropriately within the site’s source documents. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient. j. Participant must agree to not breastfeed during the study or for 180 days after the last dose of study treatment. k. Participant must be able to understand the study procedures and agree to participate in the study by providing written informed consent
Exclusion Criteria
- Participant must not be simultaneously enrolled in any interventional clinical trial 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) Participant must not have had major surgery≤3 weeks prior to initiating protocol therapy and participant must have recovered from any surgical effects 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 Participant has had radiation therapy encompassing>20%of the bone marrow within 2 weeks; or any radiation therapy within 1 week prior to Day1 of protocol therapy Participant has not recovered to Grade1 or baseline from all toxicities associated with previous therapy Participant must not have a known hypersensitivity to niraparib and dostarlimab components or excipients and must not have any hypersensitivity to the treatment used as standard of care in the control arm Participant must not show contraindications to other agents(including chemotherapy)used in this study Participant must not have received a transfusion (platelets or red blood cells) Participant must not have received colony-stimulating factors within 4 weeks prior initiating protocol therapy Participant has had any known Grade 3 or 4 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted>4weeks and was related to the most recent treatment Participant must not have a diagnosis of Sars-CoV-2 infection at the time of screening Participant must not have any known history of myelodysplastic syndrome or acute myeloid leukemia Participant must not have a serious, uncontrolled medical disorder, nonmalignant systemic disease, or active, uncontrolled infection 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) Participant must not have known, symptomatic brain or leptomeningeal metastases Patient experienced≥Grade 2 immune-related AE with prior immunotherapy with the exception of non-clinically significant lab abnormalities Participant has a diagnosis of immunodeficiency or has an active autoimmune disease that has required systemic treatment in the past 2years or has received systemic steroid therapy at a dose>10 mg/day or any other form of immunosuppressive therapy within 7days prior to initiating protocol therapy. Local or systemic corticosteroid treatment at a dosage less than or equal to 10 mg/day is allowed Participant has a known history of human immunodeficiency virus Participant has known active hepatitis B or hepatitis C Participant has an active infection requiring systemic therapy Participant must not have a history of interstitial lung disease Participant has had an allogenic tissue/solid organ transplant 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 Has received a live vaccine within 30days of planned start of study therapy while participating in the trial and within90days of the last dose of study medication Women with childbearing potential if they do not agree with the use of highly effective contraceptive methods with low user dependency or to be abstinent from heterosexual intercourse during the treatment period and at least 180days following the last dose of dostarlimab or niraparib and at least 210 days following the last dose of chemotherapy
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Czechia | Recruiting | 16 Dec 2020 | 32 |
 France | Recruiting | 16 Dec 2020 | 126 |
 Germany | Recruiting | 16 Dec 2020 | 40 |
 Italy | Recruiting | 16 Dec 2020 | 229 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
TOPOTECAN | Comparator | PHF00006MIG | INTRAVENOUS USE | 1.25 | 24 | SCP1673661 |
DOSTARLIMAB | Test | PHF00230MIG | SOLUTION FOR INFUSION | 1000 | 24 | SCP49648890 |
BEVACIZUMAB | Comparator | PHF00230MIG | INTRAVENOUS USE | 15 | 24 | SCP29096188 |
PACLITAXEL | Comparator | PHF00230MIG | INTRAVENOUS USE | 80 | 24 | SCP129816 |
NIRAPARIB | Test | PHF00006MIG | ORAL USE | 300 | 24 | SCP28153695 |
DOXORUBICIN | Comparator | PHF00231MIG | CONCENTRATE FOR SOLUTION FOR INFUSION | 50 | 24 | SCP138158 |
GEMCITABINE | Comparator | PHF00230MIG | INTRAVENOUS USE | 1000 | 24 | SCP1128788 |