TAILOR-PANC: Molecularly Tailored Therapy Versus Standard Care in Advanced Pancreatic Cancer (DPCG-02)
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 1,200
- 试验地点
- 4
- 主要终点
- Progression-Free Survival in Randomized Participants
研究概览
简要总结
Pancreatic cancer that has spread or cannot be removed by surgery is difficult to treat. Standard chemotherapy can slow the disease, but the cancer often starts growing again. Some pancreatic cancers have specific genetic changes that may be targeted by medicines already available in Denmark. It is not yet known whether selecting treatment based on these genetic changes is more effective than standard treatment.
TAILOR-PANC is a randomized phase 2 study evaluating treatment guided by the molecular characteristics of the cancer. Adults with advanced pancreatic cancer whose disease has progressed during or after first-line chemotherapy may participate if molecular testing results are available. A national molecular tumor board will review these results and determine whether the cancer has a genetic change that can be matched to an available targeted treatment.
Participants with a suitable genetic change will be randomly assigned in a 1:1 ratio to receive either the matched treatment recommended by the molecular tumor board or standard second-line treatment according to Danish guidelines. Participants without a suitable genetic change will receive standard treatment and will be followed in a separate observational group. Treatment will continue until the cancer progresses, unacceptable side effects occur, the participant withdraws consent, or the treating physician decides that treatment should stop.
The main purpose of the study is to determine whether molecularly matched treatment delays cancer progression compared with standard treatment. The study will also evaluate overall survival, tumor response, side effects, and quality of life. Participants in the randomized groups will undergo scans, blood tests, and quality-of-life assessments at baseline and approximately every 8 weeks. Optional blood and tumor samples may also be collected through the BIOPAC project to explore biomarkers that could help predict treatment response or side effects.
详细描述
TAILOR-PANC (DPCG-02) is an investigator-initiated, multicenter, randomized phase 2 trial evaluating whether molecularly tailored second-line therapy improves outcomes compared with standard-of-care treatment in patients with advanced pancreatic cancer.
Although most pancreatic cancers harbor KRAS mutations, a smaller proportion contain potentially actionable molecular alterations, including selected mutations, gene fusions, amplifications, or biomarkers such as mismatch repair deficiency. Some of these alterations can be targeted by medicines that are already available in Denmark, although the medicines may have been developed or approved primarily for other cancer types. Observational studies suggest that patients with pancreatic cancer who receive treatment matched to an actionable alteration may have better outcomes than patients who receive non-matched treatment. However, this strategy has not been adequately evaluated in a randomized setting.
Molecular profiling is performed before study allocation using tumor tissue and/or blood. Whole-genome sequencing is preferred, but targeted next-generation sequencing or whole-exome sequencing may be used when whole-genome sequencing is unavailable. The results are summarized in a personalized molecular report. A national multidisciplinary molecular tumor board, including pancreatic cancer oncologists, molecular biologists, pathologists, and computational biologists, reviews the molecular findings and assesses whether an alteration is clinically actionable. A molecular alteration is considered actionable when it can be matched to a specific anticancer treatment supported by clinical evidence and the treatment is available and reimbursed in Denmark.
Participants whose cancers harbor an actionable, reimbursed molecular alteration are randomized in a 1:1 ratio to:
Arm 1: molecularly tailored therapy selected according to the recommendation of the national molecular tumor board; or Arm 2: standard second-line therapy according to Danish clinical guidelines.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Adult patients (aged 18 and over)
- •PC confirmed by cytology or histology
- •Written informed consent before any specific study procedures
- •Available personalized report communicating the molecular testing results and detailed treatment options
- •Participants must have received and progressed during or after 1 line of systemic chemotherapy in the advanced setting (gemcitabine or 5-FU based regimens) or within one year of the adjuvant/neoadjuvant treatment
- •In general, discontinuation of 1 drug in a multi-drug regimen and continuation of other drug(s), is considered part of the same line of treatment. Restarting the same regimen after a drug holiday or maintenance chemotherapy can also be considered part of the same line of treatment
- •Switching from IV (5-FU) to an oral formulation (capecitabine) of the same drug is also considered part of the same line of treatment
- •Minimum time from first systemic therapy for advanced PC to progression should be at least 2 months
- •ECOG Performance Status (PS) 0-2
- •Participants must have normal organ and marrow function as defined below:
- •Absolute neutrophil count (ANC) ≥ 1.5 x 10⁹/L
- •Platelet count ≥ 75 x 10⁹/L
- •Serum bilirubin ≤ 1.5 x upper limit of normal (ULN)
- •AST/ALT ≤ 5 x ULN
- •Serum creatinine ≤ 1.5 x ULN or CrCl ≥ 50 mL/min (using the Cockcroft-Gault formula)
- •Women of childbearing potential (WOCBP) must use method(s) of contraception as indicated in the protocol
- •Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year
排除标准
- •Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results
- •Allergies and Adverse Drug Reaction
- •History of allergy to study drug components
- •History of severe hypersensitivity reaction to any monoclonal antibody (applicable for participants to receive a monoclonal antibody in the trial)
- •WOCBP who are pregnant or breastfeeding
研究组 & 干预措施
Arm 1: Molecularly Tailored Therapy
Participants with an actionable, reimbursed molecular alteration will receive molecularly tailored treatment selected on a case-by-case basis following review by the national molecular tumor board. The treatment will be matched to the identified alteration and may differ between participants. Treatment will be administered according to the relevant drug-specific requirements and continued until disease progression, unacceptable toxicity, withdrawal of consent, or clinical deterioration based on the investigator's judgment.
干预措施: Arm 1: Molecularly Tailored Therapy (Drug)
Arm 2: Standard-of-Care Therapy
Participants with an actionable, reimbursed molecular alteration who are randomized to this arm will receive standard second-line systemic therapy according to current Danish clinical guidelines. The specific treatment will be selected by the treating investigator based on previous therapy, clinical condition, and applicable guidelines. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or clinical deterioration based on the investigator's judgment.
干预措施: Arms 2: Standard-of-Care Therapy (Drug)
Arm 3: Standard-of-Care Observational Cohort
Participants without an actionable, reimbursed molecular alteration will not undergo randomization. They will receive standard-of-care therapy according to current Danish clinical guidelines and will be followed as a non-randomized observational cohort. Treatment selection, assessments, and follow-up will be performed as part of routine clinical care. Data from this cohort will support exploratory comparisons with participants whose cancers contain actionable molecular alterations.
干预措施: Arm 3: Standard-of-Care Observational Cohort (Drug)
结局指标
主要结局
Progression-Free Survival in Randomized Participants
时间窗: 1 year
Progression-free survival is defined as the time from the first dose of study treatment to investigator-assessed objective disease progression according to RECIST version 1.1 or death from any cause in the absence of documented progression, whichever occurs first. Participants without progression or death at the analysis will be censored at their latest evaluable RECIST assessment. The primary comparison is between molecularly tailored therapy (Arm 1) and standard-of-care therapy (Arm 2).
次要结局
- Overall Survival in Randomized Participants(1 year)
- Overall Survival Rate at 6 Months(6 months)
- Overall Survival Rate at 12 Months(12 months)
- Confirmed Objective Response Rate(1 year)
- Disease Control Rate at 4, 6, and 12 Months(12 months)
- Duration of Response(1 year)
- Progression-Free Survival After Subsequent Therapy(1 year)
- Incidence and Severity of Treatment-Related Adverse Events(1 year)
- Change From Baseline in EORTC QLQ-C30 Scores(1 year)