EUCTR2017-003552-23-GB进行中（未招募）1 期
A Phase 1b-2 Study of Niraparib Combination Therapies for the Treatment of Metastatic Castration-Resistant Prostate Cancer - QUEST
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 140
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional clinical trial of medicinal product
入排标准
- 性别
- Male
入选标准
- •1. 18 years of age or older
- •2. Willing to undergo all protocol-specified biopsies
- •3. Diagnosis of prostate adenocarcinoma as confirmed by the investigator.
- •4. Criterion moved per Amendment 3.
- •5. Criterion moved per Amendment 3
- •6. Criterion moved per Amendment 3
- •7. Must have castrate levels of testosterone =50 ng/dL on a gonadotropin releasing hormone analogue (GnRHa), or history of bilateral orchiectomy at study entry
- •8. Progression of metastatic prostate cancer at study entry defined as having one or more of the following:
- •a. PSA progression defined by a minimum of 2 rising PSA levels with an interval of =1 week between each determination (per Prostate Cancer Working Group 3 [PCWG3] criteria). The PSA level at the screening visit should be =2 µg/L (2 ng/mL).
- •b. Radiographic progression by bone scan per PCWG3 or by soft tissue per RECIST 1.1.
- •9. Must be willing to continue GnRHa during the study if not surgically castrate.
- •10. Eastern Cooperative Oncology Group Performance Score (ECOG PS) Grade of 0 or 1
- •11. Subjects who received prior therapy with an anti-androgen (eg, bicalutamide, flutamide, nilutamide, enzalutamide, apalutamide) must
- •have at least a 4-week wash-out prior to enrollment.
- •12.Criterion modified per Amendment 6.
- •12.1 While on study medication and for 3 months (Combination 2) or 5 months (Combination 1) following the last dose of study medication, a male subject must agree to use an adequate contraception method as deemed appropriate by the investigator and as specified in Section 4.4 Lifestyle Considerations.
- •13. Clinical laboratory values at Screening:
- •a.Absolute neutrophil count (ANC) =1.5 x 10^9/L, independent of growth factors for 30 days
- •b.Hemoglobin =9.0 g/dL, independent of growth factors or transfusions for 30 days
- •c.Platelet count =100 x 10^9/L, independent of growth factors or transfusions for 30 days
- •d.Serum albumin =3.0 g/dL
- •e.Creatinine clearance =30 mL/min/1.73 m^2 either calculated or directly measured via 24-hour urine collection
- •f.Serum total bilirubin =1.5 x upper limit of normal (ULN) or direct bilirubin =1 x ULN (Note: in subjects with Gilbert’s syndrome, if total bilirubin is >1.5 x ULN, measure direct and indirect bilirubin, and if direct bilirubin is =1.5 x ULN, subject may be eligible as determined by the medical monitor)
- •g.Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =3 x ULN
- •h.Fasting glucose =250 mg/dL
- •14.A male subject must agree not to donate sperm while on study treatment and for 3 months (Combination 2) or 5 months (Combination 1)following the last dose of study medication.
- •Combination 1: Niraparib and Cetrelimab.
- •1.Criterion modified per Amendment 4.
- •1.1 Must have determination of biomarker positive for DRD OR CDK12(biallelic) by
- •the sponsor's blood or tissue assay. For Part 1 of the study, subjects can
- •be dosed prior to assay results becoming available. Results are required
- •prior to dosing for Part 2.
- •2. Subjects must have measurable disease as defined by RECIST 1.1
- •(soft tissue lesion of =10mm in the long axis or extrapelvic lymph node
- •of =15mm in the short axis).
- •3. Must have previously received at least 1, but no more than 2, lines of
- •novel AR-targeted therapy (ie, abiraterone acetate with prednisone,
- •enzalutamide) for mCRPC. Subjects must have had at least 4 weeks of
- •AR-targeted therapy.
- •Combination 2: Niraparib and AAP
- •1. Must be biomarker positive for DRD by either blood or tissue assay
- •2. Must have progressed on 1 prior line of novel AR-targeted therapy
排除标准
- •1. Prior treatment with a poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor.
- •2. History or current diagnosis of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML).
- •3. Criterion modified per Amendment 5.
- •Active malignancies (ie, progressing or requiring treatment change in the last 24 months) other than the disease being treated under study. The only allowed exceptions please refer to protocol.
- •4. Active infection requiring systemic therapy.
- •5. Allergies, hypersensitivity, or intolerance to niraparib or the corresponding excipients (refer to the Investigator’s Brochures).
- •6. Human immunodeficiency virus (HIV)-positive subjects with 1 or more of the following:
- •a. Not receiving highly active antiretroviral therapy.
- •b. A change in antiretroviral therapy within 6 months of the start of screening (except if, after consultation with the sponsor on exclusion criterion 11.c, a change is made to avoid a potential drug-drug interaction with the study drug).
- •c. Receiving antiretroviral therapy that may interfere with the study drug
- •(consult the sponsor for review of medication prior to enrollment).
- •d. CD4 count <350 cells/mm^3 at screening.
- •e. An acquired immunodeficiency syndrome-defining opportunistic infection within 6 months of the start of screening.
- •7. Active hepatitis B virus (eg, hepatitis B surface antigen reactive) or active hepatitis C virus (HCV) (eg, HCV ribonucleic acid [RNA] [qualitative] is detected).
- •8. If a subject has undergone major surgery, they must have recovered adequately from the toxicities or complications from the intervention prior to starting therapy.
- •9. Criterion deleted per Amendment 2.
- •10. Any of the following =30 days prior to planned Cycle 1 Day 1:
- •a.A transfusion (platelets or red blood cells).
- •b.Hematopoietic growth factors.
- •c.An investigational agent for prostate cancer.
- •d.Major surgery (sponsor's medical monitor should be consulted regarding what constitutes major surgery).
- •e.Radiation therapy
- •11. Symptomatic brain metastasis from prostate cancer.
- •12. Symptomatic congestive heart failure (New York Heart Association
- •Class III or IV heart disease), unstable angina pectoris, cardiac arrhythmia, or uncontrolled hypertension defined as systolic blood pressure [BP] >160 mmHg or diastolic BP >100 mmHg). Note that subjects with a history of hypertension are allowed, if BP is controlled to within these limits by anti-hypertensive treatment.
- •13. Any condition for which, in the opinion of the investigator or medical monitor, participation would not be in the best interest of the subject (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
- •For excl.criteria to combination 1: Niraparib and Cetrelimab:
- •1. Criterion deleted per Amendment 2.
- •2. Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 antibody (including any antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
- •3. Subjects with a history of allergy to protein-based therapies or any significant drug allergy (ie, anaphylaxis, heptatotoxicity, or immune-mediated thrombocytopenia or anemia).
- •4. History of (non-infectious) pneumonitis that required corticosteroids or current pneumonitis.
- •5. Allergies, hypersensitivity, or intolerance to Cetrelimab or the corresponding excipients (refer to the Investigator’s Brochure).
- •6. Immunodeficiency or receiving systemic corticosteroid therapy or immunosuppressive therapy (eg, cyclosporine) within 7 days
研究者
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