Randomized Phase II Trial Evaluating the Efficacy of a Sequential Treatment Gemcitabine Plus Nab-paclitaxel (Gembrax) Followed by Folfirinox Versus Folfirinox Alone in Patients Treated in First Metastatic Line Pancreatic Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 162
- 试验地点
- 8
- 主要终点
- Progression-free survival
研究概览
简要总结
The aim of this study is to evaluate the efficacy of sequential treatment (Gabrinox) comprising Gembrax regimen (Gemcitabine -Abraxane) followed by the Folfirinox regimen (5FU, Oxaliplatin and Irinotecan) compared to folfirinox alone in patients treated in first metastatic line pancreatic cancer
详细描述
Pancreatic cancer is the third leading cause of cancer death in 2016, surpassing breast cancer. It is estimated that by 2030 pancreatic cancer will become the second leading cause of cancer death after lung cancer.
Its prognosis is very poor, with a 5-year overall survival rate (OS) at all stages of 5.5%.
In France, its incidence doubled in men and tripled in women between 1982 and 2012. The World Standardized Rate (MSR) for men and women respectively was 4.9% and 2% in 1980 and 10.2% and 6.9% in 2012. This means an annual rate of change of 2.3 for men to 3.9 for women.
Its diagnosis is often late, carried out in 50% of cases at stage 4, with limited treatment options, explaining its low survival rate at 5 years.
Until 2011, gemcitabine remained the only validated standard with a median survival of 6 months.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female aged 18 to 75 on the date the consent is signed.
- •Histologically or cytologically proven metastatic pancreatic adenocarcinoma. The definitive diagnosis of pancreatic adenocarcinoma metastases will be made by integrating the histopathological data in the context of the radiological data.
- •One or more metastatic lesion (s) measurable (Recist 1.1) by Thoraco-Abdomino-Pelvic scanner (or hepatic MRI and Thoraco-Abdomino-Pelvic scanner not injected, if the patient is allergic to the product of contrast).
- •Previous treatment (including radiochemotherapy) for the non-metastatic disease authorized if a delay ≥ 6 months between the last treatment and the recurrence is respected.
- •WHO performance status ≤ 1
- •Uracilemia <16 ng / ml
- •Acceptable hematological assessment at inclusion (obtained within 14 days before the start of treatment) defined by: • Neutrophils ≥ 2 × 109 / L; • Platelets ≥ 100,000 / mm3 (100 × 109 / L); • Hemoglobin ≥ 9 g / dl.
- •Acceptable renal and hepatic function at inclusion (obtained within 14 days before the start of treatment) defined by: • AST and ALT ≤ 2.5 x upper limit of the norm (ULN), unless liver metastases are present in this case AST and ALT ≤ 5 × ULN is allowed; • Total bilirubin ≤ 1.5 x ULN; • Serum creatinine within the norm limits or calculated clearance ≥ 50ml / min for patients with a serum creatinine value above or below the norm values (clearance calculated by the CKD-EPI formula).
- •Calcemia AND magnesemia AND kalaemia ≥ LLN and ≤ 1.2 x ULN
- •If the patient is sexually active, he must agree to use contraception deemed adequate and appropriate by the investigator throughout the period of administration of the study drug and up to 6 months after discontinuation of treatment for women and for men.
- •Signature of consent before any procedure specific to the study.
- •Affiliated with the French national social security.
排除标准
- •Known brain metastasis.
- •Previous treatment with radiotherapy, surgery, chemotherapy or experimental therapy for the treatment of metastatic disease.
- •Major surgery, other than diagnostic surgery (that is, surgery done to obtain a diagnostic biopsy without organ harvesting), within 4 weeks of day 1 of study treatment.
- •Known Gilbert's syndrome or homozygous for know UGT1A1 * 28
- •Other concomitant cancer or history of cancer, except cervical cancer in situ treated, skin basal or squamous cell carcinoma, superficial bladder tumor (Ta, Tis, and T1) or a tumor with a good prognosis treated curatively without chemotherapy and without any sign of disease in the 3 years preceding inclusion.
- •Patients with high cardiovascular risk, including, but not limited to, coronary stent or myocardial infarction within the past 6 months.
- •Peripheral sensory neuropathy ≥ grade 2 at the time of inclusion.
- •ECG with a QTc interval greater than 450 ms for men and greater than 470 ms for women
- •Any other concomitant and unbalanced disease or serious disturbance that may interfere with the patient's participation in the study and his safety during the study (eg severe hepatic, renal, pulmonary, metabolic, or psychiatric disorders)
- •Allergy or intolerance to any study drug (gemcitabine, nab-paclitaxel, oxaliplatin, irinotecan, 5-FU) or any excipient (e.g., fructose) as described in the sections " contraindication or special warnings and precautions" or "prescribing information" of the summary of product characteristics indications.
- •Pregnant or breastfeeding women. Women of childbearing potential must have a negative pregnancy test (serum β-hCG) within 72 hours prior to inclusion.
- •Patients on vitamin K antagonists (e.g., Coumadin) (modifications to treatment may be required prior to inclusion).
- •Treatment with brivudine within 4 weeks before or after treatment with 5-fluorouracil (due to a potentially fatal interaction).
- •Active and uncontrolled bacterial, viral, or fungal infections requiring systemic treatment.
- •Active HIV infection, known hepatitis B or C infection.
- •History of peripheral arterial disease (e.g., claudication, Buerger's disease), chronic inflammatory bowel disease or rectal disease, pulmonary fibrosis or interstitial pneumonia.
- •Administration of a live attenuated vaccine within 10 days before inclusion and up to 6 months post-treatment.
- •Patient refusal or inability to comply with study procedures.
- •Inability to undergo follow-up for geographical, social, or psychological reasons.
- •Participation in another clinical trial involving an investigational product within the 30 days prior to inclusion.
- •Legal incapacity (patient under guardianship or guardianship).
研究组 & 干预措施
GEMBRAX/FOLFIRINOX Arm A
One cycle:
- D1, D8 and D15 GEMBRAX: Albumin bound paclitaxel 125mg / m² followed by Gemcitabine 1000mg / m² followed by 2 weeks of rest
- D29 and D43 FOLFIRINOX: Oxaliplatin 85mg / m², Irinotecan 180mg / m², Folinic acid 400 mg / m², 5-fluorouracil 400mg / m² in bolus followed by continuous administration over 46h at 2400mg / m² followed by 2 weeks of rest.
A maximum of 6 cycles (12 months) of chemotherapy will be administered to patients in arm A.
干预措施: GEMBRAX/FOLFIRINOX Arm A (Combination Product)
FOLFIRINOX Arm B
One cycle :
D1, D15, D29 and D43 FOLFIRINOX: Oxaliplatin 85mg / m², Irinotecan 180mg / m², Folinic acid 400mg / m², 5-fluorouracil 400mg / m² as a bolus followed by continuous administration over 46h at 2.400mg / m² followed by 2 weeks of rest.
A maximum of 3 cycles (6 months) of chemotherapy will be administered to patients in arm B.
干预措施: FOLFIRINOX Arm B (Combination Product)
结局指标
主要结局
Progression-free survival
时间窗: From randomization to disease progression or death, up to 6 month
To compare progression-free survival between the investigational treatment (Arm A) and the standard treatment (Arm B) in patients with metastatic 1st line pancreatic adenocarcinoma. Progression-free survival defined as the time between randomization and the onset of the 1st documented progression or death from any cause. Tumor progression is assessed according to the RECIST 1.1 criteria and by the centralized review.
次要结局
- Objective response rate(From randomization to the best response (complete or partial response) during treatment, up to 6 month)
- Disease control rate(From randomization to the complete or partial response or stability, up to 6 month)
- Overall survival(From randomization to death, up to 2 years)
- Quality of life questionnaire -Core 30 (QLQ-C30)(At inclusion, then every 2 months up to 12 months then at 16 months, 20 months and 24 months (2 years))
- Quality of life questionnaire -PAN 26(At inclusion, then every 2 months up to 12 months then at 16 months, 20 months and 24 months (2 years))
- Collection of circulating tumor DNA (ctDNA)(At inclusion and when treatment is stopped (approximately 6 month))
- Objective response rate(From randomization to the best response (complete or partial response) during treatment, up to 6 month)
- Disease control rate(From randomization to the complete or partial response or stability, up to 6 month)
- Tolerability of treatments(From randomization to 30 days after end of treatment, up to 13 month for Arm A and 7 month for Arm B)
- Collection of circulating tumor DNA (ctDNA)(At inclusion and when treatment is stopped (approximately 6 month))
- Overall survival(From randomization to death, up to 2 years)
- Quality of life questionnaire -Core 30 (QLQ-C30)(At inclusion, then every 2 months up to 12 months then at 16 months, 20 months and 24 months (2 years))
- Quality of life questionnaire -PAN 26(At inclusion, then every 2 months up to 12 months then at 16 months, 20 months and 24 months (2 years))