A Phase 1b Study of Gemcitabine and Leflunomide in Patients With Unresectable Pancreatic Cancer
概览
- 阶段
- 1 期
- 干预措施
- Cholestyramine
- 疾病 / 适应症
- Advanced Pancreatic Adenocarcinoma
- 发起方
- City of Hope Medical Center
- 入组人数
- 19
- 试验地点
- 2
- 主要终点
- Dose limiting toxicities (DLTs)
- 状态
- 招募中
- 最后更新
- 19天前
概览
简要总结
This phase Ib trial tests the safety, side effects, and best dose of leflunomide in combination with gemcitabine in treating patients with pancreatic cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) and cannot be removed by surgery (unresectable). Improving the effectiveness of gemcitabine without increasing side effects could lead to a greater impact for pancreatic cancer patients' survival and quality of life. Gemcitabine is commonly used as a first-line chemotherapy treatment for pancreatic cancer. Leflunomide is a drug approved for use against rheumatoid arthritis that is being looked at as a cancer treatment option. It has shown promising results when combined with gemcitabine. Giving gemcitabine in combination with leflunomide may be safe and effective in treating patients with advanced unresectable pancreatic cancer.
详细描述
PRIMARY OBJECTIVE: I. To evaluate the safety and tolerability of gemcitabine in combination with leflunomide and determine the recommended Phase 2 dose (RP2D) of the combination. SECONDARY OBJECTIVES: I. To evaluate the progression-free (PFS) and overall survival (OS). II. To evaluate the overall response rate (ORR), including confirmed and unconfirmed, complete and partial response and stable disease. III. To describe quality of life utilizing the Functional Assessment of Cancer Therapy: General (FACT-G) questionnaire. EXPLORATORY OBJECTIVES: I. To describe the pharmacokinetic profile of leflunomide when given in combination with gemcitabine. II. To examine the relationship between pharmacokinetics and disease progression. OUTLINE: Patients receive gemcitabine intravenously (IV) over 30 minutes on days 1, 8, and 15 of each cycle and leflunomide orally (PO) once daily (QD) on days -3 to -1 prior to cycle 1 and days 1-28 of each cycle thereafter. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive cholestyramine PO three times a day (TID) for 11 days at the end of treatment in the absence of unacceptable toxicity. Patients also undergo computed tomography (CT), magnetic resonance imaging (MRI), or other imaging scans as clinically indicated throughout the study, as well as blood sample collection on study and during follow up. After completion of study treatment, patients are followed up at 30 days then up to 1 year.
研究者
入排标准
入选标准
- •Documented informed consent of the participant and/or legally authorized representative.
- •Adult patients lacking capacity to consent may participate if they have a caretaker that could ensure oral medication compliance.
- •Agreement to allow the use of archival tissue from diagnostic tumor biopsies.
- •If unavailable, exceptions may be granted with study principal investigator (PI) approval.
- •Age: ≥ 18 years.
- •Eastern Cooperative Oncology Group (ECOG) ≤
- •Subjects must have histologically or cytologically confirmed diagnosis of advanced unresectable pancreatic ductal adenocarcinoma (PDA).
- •Measurable or evaluable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1
- •Potential patients must have plans of receiving single agent gemcitabine.
- •Fully recovered from the acute toxic effects (except alopecia or neuropathy) to ≤ grade 1 to prior anti-cancer therapy.
排除标准
- •Chemotherapy, radiation therapy, biological therapy, immunotherapy within 21 days prior to day 1 of protocol therapy.
- •Drugs metabolized by CYP2C8, CYP1A2, BCRP, OATP1B1/B3, and OAT3 transporters within 21 days prior to day 1 of protocol therapy.
- •Herbal medications (excluding cannabidiol \[CBD\]).
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent.
- •Issues with tolerating oral medication (e.g. inability to swallow pills, malabsorption issues, ongoing nausea or vomiting).
- •Positive for tuberculosis or latent tuberculosis (TB).
- •Active diarrhea.
- •Clinically significant uncontrolled illness.
- •Active infection requiring antibiotics.
- •Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection. (\*If seropositive for HIV, HCV or HBV, nucleic acid quantitation must be performed. Viral load must be undetectable.)
研究组 & 干预措施
Treatment (gemcitabine, leflunomide)
Patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15 of each cycle and leflunomide PO QD on days -3 to -1 prior to cycle 1 and days 1-28 of each cycle thereafter. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive cholestyramine PO TID for 11 days at the end of treatment in the absence of unacceptable toxicity. Patients also undergo CT, MRI, or other imaging scans as clinically indicated throughout the study, as well as blood sample collection on study and during follow up.
干预措施: Cholestyramine
Treatment (gemcitabine, leflunomide)
Patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15 of each cycle and leflunomide PO QD on days -3 to -1 prior to cycle 1 and days 1-28 of each cycle thereafter. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive cholestyramine PO TID for 11 days at the end of treatment in the absence of unacceptable toxicity. Patients also undergo CT, MRI, or other imaging scans as clinically indicated throughout the study, as well as blood sample collection on study and during follow up.
干预措施: Gemcitabine
Treatment (gemcitabine, leflunomide)
Patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15 of each cycle and leflunomide PO QD on days -3 to -1 prior to cycle 1 and days 1-28 of each cycle thereafter. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive cholestyramine PO TID for 11 days at the end of treatment in the absence of unacceptable toxicity. Patients also undergo CT, MRI, or other imaging scans as clinically indicated throughout the study, as well as blood sample collection on study and during follow up.
干预措施: Magnetic Resonance Imaging
Treatment (gemcitabine, leflunomide)
Patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15 of each cycle and leflunomide PO QD on days -3 to -1 prior to cycle 1 and days 1-28 of each cycle thereafter. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive cholestyramine PO TID for 11 days at the end of treatment in the absence of unacceptable toxicity. Patients also undergo CT, MRI, or other imaging scans as clinically indicated throughout the study, as well as blood sample collection on study and during follow up.
干预措施: Biospecimen Collection
Treatment (gemcitabine, leflunomide)
Patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15 of each cycle and leflunomide PO QD on days -3 to -1 prior to cycle 1 and days 1-28 of each cycle thereafter. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive cholestyramine PO TID for 11 days at the end of treatment in the absence of unacceptable toxicity. Patients also undergo CT, MRI, or other imaging scans as clinically indicated throughout the study, as well as blood sample collection on study and during follow up.
干预措施: Computed Tomography
Treatment (gemcitabine, leflunomide)
Patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15 of each cycle and leflunomide PO QD on days -3 to -1 prior to cycle 1 and days 1-28 of each cycle thereafter. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive cholestyramine PO TID for 11 days at the end of treatment in the absence of unacceptable toxicity. Patients also undergo CT, MRI, or other imaging scans as clinically indicated throughout the study, as well as blood sample collection on study and during follow up.
干预措施: Diagnostic Imaging
Treatment (gemcitabine, leflunomide)
Patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15 of each cycle and leflunomide PO QD on days -3 to -1 prior to cycle 1 and days 1-28 of each cycle thereafter. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive cholestyramine PO TID for 11 days at the end of treatment in the absence of unacceptable toxicity. Patients also undergo CT, MRI, or other imaging scans as clinically indicated throughout the study, as well as blood sample collection on study and during follow up.
干预措施: Leflunomide
结局指标
主要结局
Dose limiting toxicities (DLTs)
时间窗: Up to 28 days (cycle 1)
Toxicities will be graded according to Common Terminology Criteria for Adverse Events version 5.0.
Incidence of adverse events
时间窗: Up to 30 days after completion of study treatment
Toxicities will be graded according to Common Terminology Criteria for Adverse Events version 5.0.
次要结局
- Progression-free survival (PFS)(From start of protocol treatment until progression or death, and if neither event occur, the patient is at the time of last contact, assessed up to 1 year after completion of study treatment)
- Overall survival (OS)(From start of protocol treatment until death, and if the patient is alive, the patient is censored at time of last contact, assessed up to 1 year after completion of study treatment)
- Overall response rate (ORR)(Up to 1 year after completion of study treatment)
- Change in quality of life (QOL)(Baseline to 1 year after completion of study treatment)