Pilot Study of Personalized First-line Chemotherapy Choice for Patients With Advanced Pancreatic Adenocarcinoma Using Transcriptomic Signatures (PACsign)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 85
- 试验地点
- 13
- 主要终点
- Objective Response Rate (ORR) at 4 months based on thorax-abdomen-pelvis (TAP) CT scan every 8 weeks according to RECIST v1.1.
研究概览
简要总结
The aim of this study is to assess the clinical value of 5 transcriptomic signatures prognostic of chemotherapeutic sensitivity to improve the Objective Response Rate (ORR) of first-line (L1). Chemotherapy regimen (FOLFIRINOX vs Gem-nabP) will be selected based on transcriptomic signatures applied to the pre-therapeutic liver biopsy of newly diagnosed PDAC patients.
详细描述
Step 1: patients will sign a 1st informed consent prospectively for the molecular screening (RNAseq profile). 5 transcriptomic signatures will be applied for prediction of response to 5 Fluoro-Uracil (5FU), oxaliplatin, irinotecan, gemcitabine and taxane. Biomarker status will be obtained for all patients as part of good clinical practice.
Patients will be eligible for prospective step 2 only if the transcriptomic analysis is informative and the treatment can be started within 28 days.
Step 2: study treatment strategy: based on the results of transcriptomic signatures, patients will receive either FOLFIRINOX or Gem-nabP according to the following algorithm (2nd informed consent):
- Predicted to be FOLFIRINOX sensitive (regardless of sensitivity to Gem-nabP) = FOLFIRINOX
- Predicted to be FOLFIRINOX and Gem-nabP resistant = FOLFIRINOX
- Presence of a germline breast cancer (BRCA) mutation (regardless of transcriptomic signature) = FOLFIRINOX (tumors sensitive to platinum).
- Predicted to be Gem-nabP sensitive and FOLFIRINOX resistant = Gem-nabP
Chemotherapy with FOLFIRINOX and Gemcitabine plus nab-paclitaxel will be administered as in routine practice, according to their approval. Dose adaptation will be allowed according to investigator's usual practice.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent obtained from the patient prior to performing any protocol-related procedures, including screening evaluations.
- •Willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
- •Histologically or cytologically proven Pancreatic Ductal Adenocarcinoma (PDAC).
- •Metastatic disease.
- •Measurable or evaluable lesions according to RECIST v1.1 criteria.
- •First-line therapy (previous neoadjuvant/adjuvant chemotherapy not allowed).
- •Age ≥ 18 years (no upper limit, patients ≥ 75 years old must have a G8 score ≥ 14).
- •3. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-
- •Availability of tumor tissue sample from the primary pancreatic tumor or liver metastasis (chemo-naïve) before inclusion in step
- •Adequate organ function, as defined by the following (blood test ≤ 7 days prior to inclusion):
- •Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) ≤ 3 x upper limit of normal (ULN) (≤ 5 ULN in case of liver metastases)
- •Total serum bilirubin ≤ 1.5 ULN
- •Serum albumin ≥ 28 g/L
- •Hemoglobin ≥ 9.0 g/dl
- •Absolute neutrophil count (ANC) ≥ 1,500/μL
- •Platelets ≥ 100,000/μL
- •Creatinine clearance ≥ 50 mL/min (MDRD).
- •No Dihydropyrimidine dehydrogenase (DPD) deficiency (normal uracil level).
- •Life expectancy ≥ 3 months.
- •a. Evidence of post-menopausal status b. (or) negative urinary or serum pregnancy test for female pre-menopausal patients.
- •Registration in a National Health Care System.
排除标准
- •Concurrent enrolment in another interventional clinical study.
- •Previous treatment with chemotherapy for pancreatic cancer.
- •Uncontrolled massive pleural effusion or massive ascites.
- •Known deficiency in UGT1A1 (homozygous UGT1A1*28 allele).
- •Active bacterial, viral, or fungal infection requiring systemic therapy, including tuberculosis, hepatitis B (known positive Hepatitis B Virus surface antigen (HBsAg) result), hepatitis C (with positive RNA), Sars-Cov-2 or human immunodeficiency virus (positive HIV 1/2 antibodies).
- •Diagnosis of any second malignancy within the last 3 years, except for adequately treated basal cell or squamous cell skin cancer, or in situ carcinoma of the cervix uteri.
- •Known active central nervous system metastases and/or carcinomatous meningitis; patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline).
- •Uncontrolled intercurrent illness, including but not limited to, symptomatic congestive heart failure or coronary disease, peripheral artery disease, severe chronic obstructive pulmonary disease, decompensated cirrhosis, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
- •Live vaccine administration within 30 days prior to the first dose of study treatment.
- •Known or suspected allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
- •History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with participation for the full duration of the trial, or is not in the best interest of the participant, in the opinion of the treating investigator.
- •Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug.
- •Major surgical procedure (as defined by the Investigator) within 4 weeks prior to the first dose of trial treatment.
- •Pregnancy/lactation.
- •Person under legal protection or tutelage or guardianship.
研究组 & 干预措施
Molecular screening for prediction of response
L1 chemotherapy regimen (FOLFIRINOX vs Gemcitabine plus nab-paclitaxel (GemnabP)) will be selected based on transcriptomic signatures applied to the pre-therapeutic biopsy of newly diagnosed PDAC patients.
干预措施: Biomarkers of tumor signatures (translational studies) (Other)
Molecular screening for prediction of response
L1 chemotherapy regimen (FOLFIRINOX vs Gemcitabine plus nab-paclitaxel (GemnabP)) will be selected based on transcriptomic signatures applied to the pre-therapeutic biopsy of newly diagnosed PDAC patients.
干预措施: Clinical value of 5 transcriptomic signatures to personalize the therapeutic decision for L1 in PDAC (Other)
结局指标
主要结局
Objective Response Rate (ORR) at 4 months based on thorax-abdomen-pelvis (TAP) CT scan every 8 weeks according to RECIST v1.1.
时间窗: 4 months
ORR, defined as the percentage of patients whose disease decreased by at least 30% (partial response - PR) and/or disappeared (complete response - CR) under treatment among patients who start treatment.
次要结局
- Overall Survival (OS)(18 months)
- Progression-Free Survival (PFS)(18 months)
- Treatment-related severe (grade 3-5) toxicities(18 months)
- Disease Control Rate (DCR)(18 months)
- Feasibility of study procedure(12 months)