NCT04895046撤回2 期
Molecularly Driven, Immune-Based, Maintenance Niraparib and Dostarlimab in Advanced Stage Cholangiocarcinoma
Walid Shaib, MD0 个研究点开始时间: 2021年10月11日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- 主要终点
- Progression Free Survival (PFS)
研究概览
简要总结
Phase II, single arm trial, evaluating molecularly selected, immune-based combination therapy in maintenance treatments for advanced cholangiocarcinoma, selecting patients on the homologous recombination deficient (HRD) signature.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject must meet all of the following applicable inclusion criteria to participate in this study:
- •Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
- •Age ≥ 18 years at the time of consent.
- •ECOG Performance Status of 0-1 within 14 days prior to registration.
- •Histological or cytological documentation of metastatic adenocarcinoma of the biliary tract per AJCC, 8th edition.
- •Measurable disease according to RECIST 1.1 within 28 days prior to registration.
- •Must have a defined HRD signature (BRCA1, BRCA2, PALB2, MRE, CHEK1, CHEK2, PTEN, ATM, ATR, BER, RPA1, RAD51, BARD1, BRIP1, FAAP20, FANCM, FAN1, NBN, EMSY, MRE11, ARID1A, BAP-1.) NOTE: Clinical Laboratory Improvement Act (CLIA)-certified assays including commercial tests (Foundation Medicine, Caris, Tempus, Guardant 360 or other platforms of next generation sequencing) will be allowed.
- •Patients must have achieved complete response (CR), partial response (PR) or stable disease (SD) after 4 to 6 months of any platinum-based therapy.
- •Prior treatment with immune therapy is allowed. Exception: prior treatment with PARP inhibitors is not allowed.
- •Prior cancer treatment must be completed at least 21 days prior to registration. Toxicities attributed to prior therapy/procedure must have resolved to Grade ≤
- •Exceptions include alopecia and oxaliplatin induced neurotoxicity ≤ Grade
- •C1D1 treatment will start no more than 28 days after completion of prior cancer treatment. Patients that are > 28 days from completion of prior treatment will need to be discussed with the sponsor-investigator.
- •Life expectancy of ≥ 16 weeks per estimation of site investigator.
- •Demonstrate adequate organ function as defined in the table in the protocol. All screening labs to be obtained within 7 days prior to registration.
- •Negative urine or serum pregnancy test done ≤ 72 hours prior to C1D1 for women of childbearing potential.
- •Women of childbearing potential and their partners, who are sexually active, must agree to the use contraception as described in the protocol.
- •Male patients must use contraception as described in the protocol.
- •Participants with known Hepatitis B viral infection that is controlled on nucleos(t)ide analogs (eg entecavir or tenofovir) per investigator discretion and will be continued for the duration of the study are eligible. NOTE: Risk of HBV reactivation should be considered in all patients and the need for anti-HBV prophylaxis should be carefully assessed prior to the initiation of anticancer therapy. Testing is not required at screening. Status should be assessed through medical history and if there is a question testing may be done at the discretion of the investigator based on local guidelines. This testing would be considered standard of care.
- •Participants who are Hepatitis C antibody positive but Hepatitis C RNA negative due to prior treatment or natural resolution of infection are eligible. Testing is not required at screening. Status should be assessed through medical history and if there is a question testing may be done at the discretion of the investigator based on local guidelines. This testing would be considered standard of care.
- •Participants known to be human immunodeficiency virus (HIV) serologically positive are eligible if they meet ALL of the following criteria:
- •Cluster of differentiation 4 ≥ 350/µL and viral load < 400 copies/mL
- •No history of acquired immunodeficiency syndrome-defining opportunistic infections within 12 months prior to registration
- •No history of HIV associated malignancy for the past 5 years
- •Concurrent antiretroviral therapy as per the most current National Institutes of Health (NIH) Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV started > 4 weeks prior to study registration NOTE: Testing is not required at screening. Status should be assessed through medical history and if there is a question testing may be done at the discretion of the investigator based on local guidelines. This testing would be considered standard of care.
- •Patients must agree to not donate blood during the study or for 90 days after the last dose of study treatment.
- •Exclusion Criteria
- •Subjects meeting any of the criteria below may not participate in the study:
- •Patient is simultaneously enrolled in any interventional clinical trial.
- •Tumor embolization ≤ 4 weeks prior to registration.
- •Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism ≤ 6 months prior to registration.
- •Evidence or history of bleeding diathesis or any hemorrhage or bleeding event > CTCAE v5.0 grade 3, ≤ 4 weeks prior to registration.
- •Radiotherapy encompassing > 20% of the bone marrow within 2 weeks prior to registration. Palliative radiation therapy to a small field >1 week prior to Day 1 of study treatment may be allowed.
- •Major surgical procedure, open biopsy, or significant traumatic injury ≤ 28 days prior to registration AND have recovered from surgery.
- •Congestive heart failure - New York Heart Association (NYHA) ≥ Class II.
- •Uncontrolled cardiac conditions (eg. unstable ischemia, uncontrolled symptomatic arrhythmia, cardiac arrhythmias requiring anti-arrhythmic therapy, corrected QT interval by Fridericia's correction formula (QTcF) prolongation > 500 ms, or patients with congenital long QT syndrome. NOTE: Pacemaker, beta blockers or digoxin are permitted.
- •Ongoing infection > Grade 2 National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.
- •Patient taking medications with a known risk to prolong the QTc interval and/or cause Torsades de Pointes. NOTE: Patients must be discontinued ≥ 7 days of registration. Treating physicians may wish to replace the drug(s) that do not carry this risk with safe alternative(s).
- •Uncontrolled hypertension. (Systolic blood pressure > 140 mmHg or diastolic pressure > 90 mmHg despite optimal medical management).
- •Seizure disorder requiring medication.
- •Participant has leptomeningeal disease, carcinomatous meningitis, symptomatic brain metastases, or radiologic signs of CNS hemorrhage. NOTE: Participants with asymptomatic brain metastases (i.e. off corticosteroids and anticonvulsants for at least 7 days) are permitted.
- •Non-healing wound, ulcer, or bone fracture.
- •Renal failure requiring hemo-or peritoneal dialysis.
- •Steroid use of > than the equivalence of 5 mg of prednisone.
- •Participant must not have a history of interstitial lung disease.
- •Any autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- •Participant has a diagnosis of immunodeficiency or has received systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to initiating protocol therapy.
- •Participant has received a transfusion (platelets or red blood cells) ≤ 4 weeks prior to initiating protocol therapy.
- •Participant has 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.
- •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.
- •Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation.
- 另有 12 项未显示
排除标准
- 未提供
研究组 & 干预措施
Investigational Group
Experimental
Cycle 1-4 (cycle length 4 weeks): Niraparib 300 mg taken orally on days 1-21 and Dostarlimab 500 mg intravenously on day 1
Cycle 5 and above (cycle length 3 weeks): Niraparib 300 mg taken orally on days 1-21 and 1000 mg intravenously on day 1 of every other cycle
干预措施: Niraparib (Drug)
Investigational Group
Experimental
Cycle 1-4 (cycle length 4 weeks): Niraparib 300 mg taken orally on days 1-21 and Dostarlimab 500 mg intravenously on day 1
Cycle 5 and above (cycle length 3 weeks): Niraparib 300 mg taken orally on days 1-21 and 1000 mg intravenously on day 1 of every other cycle
干预措施: Dostarlimab (Drug)
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: 4-6 months
Evaluate PFS of patients who achieved a complete response (CR), partial response (PR) or stable disease (SD). PFS is defined as the date of treatment initiation (C1D1) until the criteria for disease progression is met as defined by RECIST 1.1 or death occurs
次要结局
- Frequency and Severity of Adverse Events(5 years)
- Objective Response Rate (ORR)(5 years)
- Overall Survival (OS)(5years)
- Disease Control Rate (DCR)(5 years)
- Duration of Response (DOR)(5 years)
研究者
Walid Shaib, MD
Sponsor Investigator
Hoosier Cancer Research Network
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