This is a phase 2 study of investigational drug niraparib and TSR-042 in patients with advanced/recurrent endometrial cancer. The purpose of this study is to determine whether blocking a protein called poly (ADP-ribose) polymerase (PARP) with niraparib provides clinical benefit in patients with recurrent endometrial cancer, as well as to explore the possible impact of phosphatase and tensin homolog (PTEN) loss (loss of function of the PTEN gene) on blocking PARP with niraparib.
The purpose of this trial is to elucidate whether the PARP inhibition approach with niraparib, or the combination of niraparib and TSR-042, provides clinical benefit in patients with recurrent endometrial cancer. The trial is designed as a multicenter, open-label, phase II study of niraparib in monotherapy or in combination with anti-PD1 inhibitor TSR-042 in recurrent endometrial cancer. Patients must have received prior platinum based chemotherapy. The study will initially enroll patients with recurrent endometrial cancer to the niraparib monotherapy cohort not selected according to the PTEN status (cohort I). Once the initial assessment with niraparib monotherapy is completed (inclusion of 22 evaluable patients),Additional 22 patients will be enrolled in the combination arm with niraparib and TSR-042 (cohort II). Eligible participants will take niraparib capsules or tablets by mouth 300/200 mg, once a day, every day of every 21 day cycle.Participant will receive TSR-042 500 mg( intravenously) on the first day of each cycle for cycle 1 to 4. Followed by 1000 mg every 2 cycle for every 6 weeks for maximum of 2 yrs. While receiving the study treatment, participants will be asked to visit the study site on Days 1, 8, 15 of Cycle 1.Cycle 2 onward Days 1 and 15 and future cycles for safety tests and procedures. If, at any time, participants develop (or is suspected to have developed) MDS/AML, a mandatory bone marrow aspirate/biopsy will be done for testing to confirm diagnosis. When participants are taken off the study treatment permanently, they will be asked to return to the study site for an End of Study Treatment visit to have tests and procedures done for safety purposes. Participants who are taken off the study treatment for any reason other than disease progression will continue to have radiological assessments every 8 weeks until disease progression. Participants will continue to be followed up for side effects weekly in the first 4 weeks, then monthly until resolution.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
51
Tom Baker Cancer Centre
Calgary, Alberta, Canada
Juravinski Cancer Centre
Hamilton, Ontario, Canada
Cancer Centre of Southeastern Ontario at Kingston
Kingston, Ontario, Canada
London Regional Cancer Centre
London, Ontario, Canada
To determine the antitumor activity according to RECIST v 1.1
To determine the antitumor activity of single agent niraparib and of niraparib in combination with TSR-042 in women with metastatic endometrial cancer who has received prior platinum-based chemotherapy via assessment of clinical benefit rate (complete response, partial response or stable disease ≥16 weeks), according to RECIST v 1.1.
Time frame: 16 weeks
Number of side effects
To assess the safety and tolerability of single agent niraparib and of niraparib in combination with TSR-042.
Time frame: 5 years
Overall response rate
Overall response rate (ORR) is defined as the proportion of subjects in the analysis population who have complete response (CR) or partial response (PR) at any time during the study using RECIST
Time frame: 5 years
Duration of response
The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The duration of overall CR is measured from the time measurement criteria are first met for CR until the first date that progressive disease is objectively documented.
Time frame: 5 years
Progression free survival rate
Progression free survival (PFS) is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. If such an event is not observed after 6 months of follow up, patients are censored.
Time frame: 5 years
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Sunnybrook Research Institute, Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada
Princess Margaret Cancer Centre
Toronto, Ontario, Canada
McGill University Health Centre - Glen Site
Montreal, Quebec, Canada
Overall survival rate
Overall survival time (OS) is defined as the time of registration to the date of death by any cause. Following the treatment discontinuation visit, survival status will be collected for all patients using acceptable means including telephone contact.
Time frame: 5 years