A Phase II Study of Niraparib in Combination With EGFR Inhibitor Panitumumab in Patients With Advanced Colorectal Cancer
概览
- 阶段
- 2 期
- 干预措施
- Niraparib
- 疾病 / 适应症
- Advanced Microsatellite Stable Colorectal Carcinoma
- 发起方
- Emory University
- 入组人数
- 26
- 试验地点
- 3
- 主要终点
- Clinical Benefit Rate (CBR)
- 状态
- 进行中（未招募）
- 最后更新
- 3个月前
概览
简要总结
This phase II trial studies the side effects and how well niraparib and panitumumab work in treating patients with colorectal cancer that has spread to other places in the body. Niraparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as panitumumab, may help the body's immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread. Giving niraparib and panitumumab may work better in treating patients with colorectal cancer.
详细描述
PRIMARY OBJECTIVE: I. Evaluate the activity of the combination of niraparib with epidermal growth factor receptor (EGFR) inhibitor panitumumab in previously treated patients with rat sarcoma gene (RAS) wild type (WT) metastatic colorectal cancer. SECONDARY OBJECTIVES: I. Define the toxicity profile of the combination of niraparib and panitumumab. II. Evaluate the activity of the combination of niraparib and panitumumab in previously treated patients with metastatic colorectal cancer. OUTLINE: Patients receive niraparib orally (PO) once daily (QD) on days 1-28 and panitumumab intravenously (IV) over 60-90 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days, every 6 months for 2 years, and then annually for up to 5 years.
研究者
Olatunji Alese
Principal Investigator
Emory University
入排标准
入选标准
- •Participant must have advanced, metastatic RAS wildtype colorectal cancer and must have received at least one line of systemic therapy. Both microsatellite (MSI) high and stable (MSS) patients are eligible
- •Participants may have been intolerant of, progressed on, or failed at least one line of systemic chemotherapy. Patients who are currently on first line Oxaliplatin-containing chemotherapy regimen are allowed on the trial if they have remained stable or better (\[partial response\]PR or \[complete response\]CR) for at least 4 months on that line of treatment and are being considered for maintenance therapy as standard of care
- •Histologic or cytologic diagnosis of colorectal cancer
- •Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
- •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 ≥ 30 mL/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
排除标准
- •Participant must not be simultaneously enrolled in any interventional clinical trial
- •Prior therapy with poly ADP (adenosine diphosphate) ribose polymerase (PARP) inhibitors or with EGFR inhibitors approved for the treatment of colorectal cancer (cetuximab or panitumumab)
- •Patients with a history of interstitial pneumonitis or pulmonary fibrosis, or evidence of interstitial pneumonitis or pulmonary fibrosis during screening
- •Inability to take oral medications
- •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 components or excipients of niraparib or panitumumab
- •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
- •Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
- •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)
- •Participant must not have known active, symptomatic brain or leptomeningeal metastases.
研究组 & 干预措施
Treatment (niraparib, panitumumab)
Patients receive 200 or 300 mg niraparib orally once daily on days 1-28 and 6 mg/kg panitumumab intravenously over 60-90 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Niraparib
Treatment (niraparib, panitumumab)
Patients receive 200 or 300 mg niraparib orally once daily on days 1-28 and 6 mg/kg panitumumab intravenously over 60-90 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Panitumumab
结局指标
主要结局
Clinical Benefit Rate (CBR)
时间窗: 3 years and 7 months post treatment
The efficacy, as measured by clinical benefit rate (CBR), will be assessed for the total number of patients enrolled. CBR = (Complete Response + Partial Response + Stable Disease \[CR +PR + SD\] rate. Response will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 criteria using an independent review.
次要结局
- Objective Response Rate (ORR)(Up to 5 years post treatment)
- Duration of Response (DOR)(Up to 5 years post treatment)
- Progression Free Survival (PFS)(Up to 5 years post treatment)
- Overall Survival (OS)(Up to 5 years post treatment)