Study of Niraparib and TSR-042 in Recurrent Endometrial Cancer

NCT03016338 | Unknown Phase 2 DMC

• 1 other identifier: NEC
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Endometrial Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  16 weeks

Secondary Outcomes (5)

• Number of side effects

  5 years

• Overall response rate

  5 years

• Duration of response

  5 years

• Progression free survival rate

  5 years

• Overall survival rate

  5 years

Study Arms (1)

Niraparib +TSR-042

EXPERIMENTAL

200/300 mg Niraparib by mouth once a day for 21 days cycle. 500 mg of TSR-042 intravenously on the first day of each cycle.

Drug: Niraparib; Drug: TSR-042

Interventions

Niraparib DRUG

200 or 300 mg daily PO, for 21 day cycle

Also known as: MK4827

Niraparib +TSR-042

TSR-042 DRUG

500 mg once intravenously on day 1 of cycle (From cycle 1-4 followed by 1000 mg intravenously every 6 weeks for maximum of 2 yrs)

Also known as: Dostarlimab

Niraparib +TSR-042

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed epithelial endometrial cancer. All histological subtypes are allowed except for endometrial sarcoma, carcinosarcoma, clear cell, mixed and adenosquamous tumors.
• Patients must have radiographic evidence of disease progression following the most recent line of treatment.
• Patients must have previously received at least one line of platinum-based chemotherapy. Prior hormonal and immunotherapy are allowed. There is no restriction on the total number prior lines of therapy.
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥10 mm with CT scan, MRI, or calipers by clinical exam, and ≥15mm for nodal lesions. Areas of previous radiation may not serve as measurable disease unless there is evidence of progression post radiation.
• Patients must have archival tumor sample available for PTEN analysis. If archival tissue is not available, the patient will have the option to undergo tumor biopsy.
• Eastern Cooperative Group (ECOG) performance status ≤ 2.
• Life expectancy of greater than 12 weeks.
• Within 7 days of the proposed start of treatment, patients must have normal organ and marrow function.
• Participant receiving corticosteroids may continue as long as their dose is stable for at least 4 weeks prior to initiating protocol therapy
• Patient must agree to not donate blood during the study or for 90 days after the last dose of study treatment

You may not qualify if:

• Chemotherapy or biologic agents received within 4 weeks of starting study treatment.
• Hormonal therapy within 2 weeks of starting study treatment.
• Pelvic radiotherapy (as treatment of primary disease) within 4 weeks, or palliative radiotherapy encompassing \>20% of the bone marrow within 1 week of starting study treatment.
• Previous treatment with a PARP inhibitor, or any other targeted therapy directed against the homologous recombination pathway.
• Patients who are receiving any other investigational agents.
• Ongoing ≥ Grade 2 toxicities related to prior cancer therapy, with the exceptions of alopecia, neuropathy, lymphopenia and skin depigmentation.
• Received transfusion (platelets or red blood cells) ≤4 weeks of the first dose of study treatment.
• Major surgery within 4 weeks of registration or ongoing clinically significant post-surgical complications. Study biopsy is not considered major surgery.
• Known brain metastases, except if stable for greater than 28 days following definitive treatment. The patient must have no new or progressive signs or symptoms related to the CNS disease and must be either off or taking a stable dose of corticosteroids. A scan to confirm the absence of brain metastases is not required.
• History of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML).
• History of bowel obstruction within 3 months, or other reason preventing effective oral administration of medication.
• Immunocompromised patients e.g. Human Immunodeficiency Virus (HIV) requiring treatment or active Hepatitis B or C. Prior splenectomy is allowed.
• Uncontrolled inter-current illness.
• History of other malignancy ≤ 3 years prior to registration with the exceptions of a) cone-biopsied in situ carcinoma of the cervix uteri; b) basal or squamous cell carcinoma of the skin. All second malignancies in this context should be discussed with the Principal Investigator.
• Previous treatment with anti PD-1, anti PD-L1, anti PD-L2, anti CTLA4 agents

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Tesaro, Inc.: collaborator

Study Sites (7)

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

Juravinski Cancer Centre

Hamilton, Ontario, L8V 5C2, Canada

Location

Cancer Centre of Southeastern Ontario at Kingston

Kingston, Ontario, K7L 5P9, Canada

Location

London Regional Cancer Centre

London, Ontario, N6A 4L6, Canada

Location

Sunnybrook Research Institute, Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 1M9, Canada

Location

McGill University Health Centre - Glen Site

Montreal, Quebec, H3A 3J1, Canada

Location

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

niraparib; dostarlimab

Condition Hierarchy (Ancestors)

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

Study Officials

• Amit M Oza, M.D.

  UHN - Princess Margaret Cancer Centre

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2017
• First Posted: January 10, 2017
• Study Start: November 6, 2017
• Primary Completion: January 5, 2021
• Study Completion: December 1, 2025
• Last Updated: January 30, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (7)