Niraparib and Dostarlimab in HRD Solid Tumors

NCT04983745 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: WCC 2020-002
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, single-arm, Phase 2 study which will evaluate the efficacy and safety of niraparib and dostarlimab (TSR-042) combination in patients with metastatic, recurrent, or unresectable solid tumor with a pathogenic, or presumed pathogenic, somatic homologous recombination deficiency (HRD) gene mutation

Conditions

Homologous Recombination Deficient Solid Tumors

Outcome Measures

Primary Outcomes (1)

• ORR

  defined as the percentage of patients with CR or PR, as assessed by RECIST v.1.1 criteria using investigator review.

  2 years

Secondary Outcomes (1)

• Clinical benefit rate (CBR)

  16 weeks

Study Arms (1)

Experimental

EXPERIMENTAL

niraparib and dostarlimab

Drug: Combination drug

Interventions

Combination drug DRUG

niraparib and dostarlimab combination

Experimental

Eligibility Criteria

• Age: Up to 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Metastatic, recurrent, or unresectable solid tumor with a pathogenic, or presumed pathogenic, somatic mutation of one of the following homologous recombination deficiency (HRD) gene mutations:
• BRCA1, BRCA2, ATM, RAD51B, RAD51C, RAD54L, RAD51D, FANC/BRIP1, FANCI, FANCL, FANCN(PALB2), BARD1, CHEK1, CHEK2, CDK12, or PPP2R2A.
• Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
• Participant must be ≥ 18 years of age
• 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
• Participant must agree to not donate blood during the study or for 90 days after the last dose of study treatment.
• Female participant has a negative serum pregnancy test within 72 hours prior to taking study treatment if of childbearing potential and agrees to use a highly effective method of contraception from screening through 180 days after the last dose of study treatment, or is of non-childbearing potential. Non-childbearing potential is defined as follows (by other than medical reasons):
• ≥45 years of age and has not had menses for \>1 year

You may not qualify if:

• Participant must not be simultaneously enrolled in any interventional clinical trial
• Patients with the following malignancies will be excluded:
• Prostate cancer
• Ovarian, breast, and pancreatic patients with known germline BRCA1 or BRCA2 mutation
• Platinum sensitive ovarian cancer (defined as recurrence \> 6 months from last platinum agent), unless platinum intolerant.
• 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 to 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 Day 1 of protocol therapy.
• Participant must not have a known hypersensitivity to niraparib and dostarlimab components or excipients.
• Participant must not have received a transfusion (platelets or red blood cells) ≤ 4 weeks prior to initiating protocol therapy.
• 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.
• 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.
• Participant must not have any known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)
• 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
• Participant must not have had diagnosis, detection, or treatment of another type of cancer ≤ 2 years prior to initiating protocol therapy (except basal or squamous cell carcinoma of the skin and cervical cancer that has been definitively treated)

Sponsors & Collaborators

• West Cancer Center: lead

Study Sites (1)

West Cancer Center

Germantown, Tennessee, 38138, United States

RECRUITING

MeSH Terms

Interventions

Drug Combinations

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations

Study Officials

• Gregory Vidal, MD

  West Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Robin Patterson, RN

CONTACT

901-683-0055; rpatterson@westclinic.com

Amanda Fletcher, RN

CONTACT

901-683-0055; afletcher@westclinic.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 28, 2021
• First Posted: July 30, 2021
• Study Start: November 29, 2021
• Primary Completion: August 1, 2024
• Study Completion: August 1, 2025
• Last Updated: December 21, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)