Niraparib and Dostarlimab for the Treatment of Recurrent or Progressive Cervical Cancer, STAR Study
- Patient has histologically proven recurrent or progressive cervix cancer
- Patient has archival tumor tissue available or a fresh biopsy of recurrent or persistent tumor must be obtained prior to study treatment initiation
- Patient has measurable lesions by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
- Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
- Patients must have received at least one or more prior systemic treatment regimen. Chemotherapy with radiation is not considered systemic treatment
- Absolute neutrophil count (ANC) >= 1,500/uL (obtained without transfusion or receipt of colony stimulating factors within 2 weeks before obtaining sample)
- Platelets >= 100,000/uL (obtained without transfusion or receipt of colony stimulating factors within 2 weeks before obtaining sample)
- Hemoglobin >= 9 g/dL or >= 5.6 mmol/L (obtained without transfusion or receipt of colony stimulating factors within 2 weeks before obtaining sample)
- Serum creatinine =< 1.5 x upper limit of normal (ULN) or calculated creatinine clearance >= 60 mL/min using Cockcroft-Gault equation for patients with creatinine levels > 1.5 x institutional ULN (obtained without transfusion or receipt of colony stimulating factors within 2 weeks before obtaining sample)
- Total bilirubin =< 1.5 x ULN OR direct bilirubin =< 1 x ULN (obtained without transfusion or receipt of colony stimulating factors within 2 weeks before obtaining sample)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN unless liver metastases are present, in which case they must be =< 5 x ULN (obtained without transfusion or receipt of colony stimulating factors within 2 weeks before obtaining sample)
- International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (obtained without transfusion or receipt of colony stimulating factors within 2 weeks before obtaining sample)
- Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (obtained without transfusion or receipt of colony stimulating factors within 2 weeks before obtaining sample)
- Patient is able to take oral medications
- Participant receiving corticosteroids may continue as long as their dose is stable for least 4 weeks prior to initiating protocol therapy
- Participant must agree to not donate blood during the study or for 90 days after the last dose of study treatment
- If of childbearing potential, has a negative pregnancy test within 7 days prior to taking study medication or agrees to abstain from activities that could result in pregnancy from enrollment through 180 days after the last dose of study treatment, or be of non-childbearing potential. Birth control should be used from the signing of the patient consent form and for 180 days following the last dose of study drugs. Acceptable methods of birth control include: * Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: ** Oral route ** Intravaginal route ** Transdermal route * Progestogen-only hormonal contraception associated with inhibition of ovulation ** Oral ** Injectable ** Implantable * Intrauterine device * Intrauterine hormone-releasing system * Bilateral tubal occlusion * Vasectomized partner * Sexual abstinence, if the preferred and usual lifestyle of the subject * Non-childbearing potential is defined as follows (by other than medical reasons): ** >= 45 years of age and has not had menses for > 1 year ** 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
- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Note: Patients with previously treated brain metastases may participate provided they are stable for at least 4 weeks prior to the first dose of study treatment, and have not been using steroids for at least 7 days prior to study treatment
- Known additional malignancy that required active treatment within the last 2 years. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin
- Patient is considered a poor medical risk that would interfere with cooperation with the requirements of the study
- Received a transfusion (platelets or red blood cells) =< 4 weeks prior to initiating protocol therapy
- Received colony stimulating factors (e.g., granulocyte colony-stimulating factor, granulocyte macrophage colony stimulating factor, or recombinant erythropoietin) within 4 weeks prior initiating protocol therapy
- 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
- Known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)
- 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
- Pregnant or breastfeeding, or expecting to conceive children within the projected duration of the study and for 180 days after the last dose of study treatment
- Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
- Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
- Known active hepatitis B or hepatitis C
- Active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
- Not recovered to =< grade 1 or to baseline from chemotherapy induced adverse events (AEs). Note: Patient with =< grade 1 neuropathy or =< grade 2 alopecia is an exception to this criterion and may qualify for the study
- Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
- Prior cytotoxic chemotherapy, anticancer targeted small molecules (e.g., tyrosine kinase inhibitors), hormonal agents within 5 half-lives, or monoclonal antibodies (mAb) within 5 half-lives or 4 weeks (whichever is shorter) of that treatment prior to study day 1 or radiation therapy encompassing > 20% of the bone marrow within 2 weeks or any radiation therapy within 4 weeks prior to study day 1
- Major surgery =< 3 weeks prior to initiating protocol therapy and participant must have recovered from any surgical effects
- Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
- Received a live vaccine within 14 days of planned start of study therapy
- Prior treatment with a known PARP inhibitor
- Known hypersensitivity to niraparib or dostarlimab components or excipients
- Patient experienced >= grade 3 immune-related AE with prior immunotherapy, with the exception of non-clinically significant lab abnormalities
- History of interstitial lung disease
I. To evaluate the efficacy of combination treatment with dostarlimab and niraparib for patients with recurrent or progressive cervical cancer.
I. To evaluate the safety of combination treatment with dostarlimab and niraparib as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.
II. To evaluate duration of response, progression free survival time and overall survival time of combination treatment with dostarlimab and niraparib in patients with recurrent or progressive cervical cancer.
I. To identify potential biomarkers that would associate with tumor response from the combination of dostarlimab and niraparib based on the molecular profile of tumor tissue, tumor infiltrating lymphocyte (TIL)s, and circulating biomarkers.
II. To correlate homologous recombination deficiency (HRD) score with other immune-related biomarkers and with treatment outcomes.
Patients receive dostarlimab intravenously (IV) on day 1 of cycles 1-4 and every 6 weeks for subsequent cycles. Patients also receive niraparib orally (PO) once daily (QD) on days 1-21. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed every 6 months for 2 years and then annually for 3 years.
Trial Phase Phase II
Trial Type Treatment
University of Oklahoma Health Sciences Center
Debra Lynn Richardson
- Primary ID OU-SCC-STAR
- Secondary IDs NCI-2020-01721
- Clinicaltrials.gov ID NCT04068753