2024-514420-16-00招募中2 期
Randomized phase 2 study of Valproic acid combinEd with rechallenge anti-EGFR based regimen regimens in pretreated patients with RAS/BRAF wild-type metastatic colorectal cancer (VICTORIA)
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 130
- 试验地点
- 9
- 主要终点
- Study Part 1_Progression-free survival (PFS) rate at 16 weeks: measured as the time from the date of randomization until the date of the first observation of disease progression or death due to any cause, whichever occurs first.
研究概览
简要总结
Study Part 1: to assess the antitumor activity of the experimental arm with panitumumab + irinotecan in combination with VPA (given until progression or inacceptable toxicity) as compared to standard treatment with panitumumab + irinotecan, measured as an improved rate of assessable patients alive at 16 weeks.
Study Part 2: to assess the antitumor activity of the addition of VPA to panitumumab + irinotecan (given until progression or inacceptable toxicity), in patients progressed to standard treatment (ARM A, irinotecan + panitumumab), measured as the rate of assessable patients alive and at 8 weeks from progression to VICTORIA - Study Part 1.
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Written informed consent to study procedures and to correlative studies.
- •Imaging-documented measurable disease, according to RECIST 1.1 criteria.
- •Estimated life expectancy of more than 12 weeks.
- •Adequate bone marrow hematological function: absolute neutrophil count (ANC) ≥ 1.5 x 109/L and platelet count ≥ 100 x 109/L and hemoglobin ≥ 9 g/dL.
- •Adequate liver function: total bilirubin ≤ 1.5 x upper limit of normal (ULN) or ≤ 2 (in case of biliary stent) and aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 5 X ULN.
- •Adequate renal function: serum creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min in males and ≥50 mL/min in females (calculated according to Cockroft-Gault formula).
- •Electrolytes (i.e. magnesium, calcium, sodium and potassium) within laboratory normal range.
- •Either sex aged ≥
- •Histologically proven of colorectal adenocarcinoma
- •Diagnosis of metastatic disease.
- •RAS/BRAF wild-type status at initial diagnosis assessed at local centers according with a validated method defined by EMA and known MMR/MSI status.
- •RAS (NRAS and KRAS exon 2,3 and 4) and BRAF wild-type in liquid biopsy at study entry (according to central testing).
- •Efficacy of anti-EGFR drug in any line of treatment with a major response achieved (i.e. complete or partial response according to RECIST criteria v1.1) or stable disease ≥ 6 months.
- •Received a subsequent line of therapy upon progression. Note. Patients must have received at least 2 lines of treatment. Previous treatment with regorafenib, trifluridine/tipiracile, fruquintinib is allowed. Previous rechallenge with anti-EGFR MoAb is NOT allowed. Adjuvant treatment will be considered as one line of therapy in case of progression within 6 months from the last dose of treatment.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1 at study entry.
排除标准
- •Prior malignancy within five years. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
- •History of poor co-operation, non-compliance with medical treatment, unreliability or any condition that may impair the patient's understanding of the Informed consent form.
- •Participation in any interventional drug or medical device study within 30 days prior to treatment start.
- •Sexually active males and females (of childbearing potential) unwilling to practice contraception (barrier contraceptive measure or oral contraception) during the study and until 6 months after the last trial treatment.
- •History of interstitial pneumonitis or pulmonary fibrosis.
- •History of corneal perforation or ulceration keratitis.
- •Any contraindication to panitumumab or irinotecan.
- •Not received immunotherapy if dMMR or MSI-H.
- •Patients who have had prior treatment with an HDAC inhibitor and patients who have received compounds with HDAC inhibitor-like activity, such as valproic acid.
- •Major surgical intervention within 4 weeks prior to enrollment.
- •Pregnancy and breast-feeding.
- •Any brain metastasis.
- •Patients with long QT-syndrome or QTc interval duration > 480 msec or concomitant medication with drugs prolonging QTc
- •Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the investigator’s opinion makes it undesirable for the patient to participate in the study, or which would jeopardize compliance with the protocol, or would interfere with the results of the study.
结局指标
主要结局
Study Part 1_Progression-free survival (PFS) rate at 16 weeks: measured as the time from the date of randomization until the date of the first observation of disease progression or death due to any cause, whichever occurs first.
Study Part 1_Progression-free survival (PFS) rate at 16 weeks: measured as the time from the date of randomization until the date of the first observation of disease progression or death due to any cause, whichever occurs first.
Study Part 2_PFS rate at 8 weeks: defined as the rate of assessable patients alive and not progressed after 8 weeks from initiation of VICTORIA - Study Part 2 (i.e End of Treatment Visit with documentation of progression to VICTORIA - Study Part 1, for patients randomized to ARM A - standard treatment).
Study Part 2_PFS rate at 8 weeks: defined as the rate of assessable patients alive and not progressed after 8 weeks from initiation of VICTORIA - Study Part 2 (i.e End of Treatment Visit with documentation of progression to VICTORIA - Study Part 1, for patients randomized to ARM A - standard treatment).
次要结局
- Study Part 1: Objective Tumor Response Rate (ORR) assessed according to RECIST criteria 1.1.
- Study Part 1: Disease Control Rate (DCR) defined as the proportion of patients with complete/partial response and stable disease as their best response.
- Study Part 1: Progression-free survival (PFS) measured as the time from the date of randomization until the date of the first observation of disease progression or death due to any cause, whichever occurs first.
- Study Part 1: Overall survival (OS) calculated as the time from the date of randomization until the date of death from any cause.
- Study Part 1: Safety evaluated as adverse events graded according NCI CTCAE v. 5.0.
- Study Part 1: Quality of life (QoL) investigated through the EORTC QLQ-C30 and CR29 questionnaires.
- Study Part 1: Patient Report Outcome (PRO)-CTCAE with items dedicated in particular to diarrhea and skin toxicity to evaluate the effect of the treatment on the health-related QoL.
- Study Part 2: Progression-free survival (PFS) measured as the time from the date from initiation of VICTORIA - Study Part 2 (i.e. at End of Treatment Visit with documentation of progression to VICTORIA - Study Part 1) until the date of the first observation of disease progression or death due to any cause, whichever occurs first.
- Study Part 2: Overall survival (OS) calculated as the time from the date from initiation of VICTORIA - Study Part 2 (i.e. at End of Treatment Visit with documentation of progression to VICTORIA - Study Part 1) until the date of death from any cause.
- Study Part 2: Objective Tumor Response Rate (ORR) assessed according to RECIST criteria 1.1.
- Study Part 2: Disease Control Rate (DCR) defined as the proportion of patients with complete/partial response and stable disease as their best response.
- Study Part 2: Safety evaluated as adverse events graded according NCI CTCAE v 5.0.
- Study Part 2: Quality of life (QoL) investigated through the EORTC QLQ-C30 and CR29 questionnaires.
- Study Part 2: Patient Report Outcome (PRO)-CTCAE with items dedicated in particular to diarrhea and skin toxicity to evaluate the effect of the treatment on the health-related QoL.
研究者
Antonio Avallone
Scientific
IRCCS Istituto Nazionale Tumori Fondazione Pascale
研究点 (9)
Loading locations...
相似试验
撤回
2 期
A Pilot Study to Evaluate the Efficacy and Safety of Neoadjuvant Chemoradiotherapy With Capecitabine, . . .Pancreatic CancerNCT01130701University of Massachusetts, Worcester
招募中
2 期
SKB264 Combinatiton Therapy in Patients With Advanced or Metastatic Non-small Cell Lung Cancer.Non-small Cell Lung CancerNCT05351788Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.110
已完成
2 期
Panitumumab and Chemotherapy in Patients With Advanced Colorectal Cancer After Prior Therapy With BevacizumabMucinous Adenocarcinoma of the ColonMucinous Adenocarcinoma of the RectumRecurrent Colon CancerRecurrent Rectal CancerSignet Ring Adenocarcinoma of the ColonSignet Ring Adenocarcinoma of the RectumStage IV Colon CancerStage IV Rectal CancerNCT01814501John Hays16
已完成
1 期
Safety Study of the Combination of Panitumumab, Irinotecan and Everolimus in the Treatment of Advanced Colorectal CancerColorectal CarcinomaColorectal TumorsNeoplasms, ColorectalColorectal CancerNCT01139138The Queen Elizabeth Hospital49
终止
2 期
Panitumumab and Irinotecan for Malignant GliomasMalignant Glioma of BrainNCT01017653Annick Desjardins16