COSENSE-1: A Feasibility Study for Using a Functional Precision Medicine Platform to Select Oxaliplatin-based Versus Irinotecan-based Chemotherapy Regimens for Patients With Metastatic Colorectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 148
- 试验地点
- 1
- 主要终点
- Test the feasibility of using a functional precision medicine platform to select oxaliplatin-based versus irinotecan-based chemotherapy regimens for patients with metastatic colorectal cancer.
研究概览
简要总结
COSENSE-1 is an unblinded, phase II, single-armed, single center feasibility study for using a functional precision medicine platform to select oxaliplatin-based versus irinotecan-based chemotherapy regimens, for male and female participants aged 18 and older, with microsatellite stable (MSS)/proficient mismatch repair (pMMR) metastatic colorectal cancer (mCRC), that is incurable or not resectable with curative intent.
详细描述
Objectives: The primary objective of this study is to test the feasibility of using a functional precision medicine platform to select oxaliplatin-based versus irinotecan-based chemotherapy regimens for patients with metastatic colorectal cancer. Secondary objectives are to describe the tumour response to treatment using efficacy measures and assess the progression-free survival and the overall survival, and assess the toxicity experienced by the participants. Exploratory objectives include basal research on tumouroids and optimisation of the functional assay to be compatible with clinical practice.
Primary endpoints: The primary endpoints are assessing feasibility:
- The rate of generating valid tumouroid response reports (valid is defined as a fold-change growth in untreated controls of > 1, registered on day 5, 6, 7 or 8 and normalised with resepect to day 0 or 1): a) per patient included in the trial and b) per patient with successful tumour sample.
- The time from referral to start of allocated treatment.
Secondary endpoints: Secondary endpoints include efficacy in the form of Response Rates (RR) graded and measured using RECIST v1.1, including Objective Response Rate (ORR), Disease Control Rate (DCR) and Clinical Benefit Rate (CBR), as well as Duration of Response (DoR), Progression Free Survival (PFS), Progression Free Survival Rate at 6 months (PFSR) and Overall Survival (OS). Toxicity will be graded using the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v.5.0).
Trial design and patient population: COSENSE-1 is an unblinded, phase II, single-armed, single-center, consent-based feasibility study for using a functional precision medicine platform to select oxaliplatin-based versus irinotecan-based chemotherapy regimens, for male and female participants aged 18 and older, with microsatellite stable (MSS)/proficient mismatch repair (pMMR) metastatic colorectal cancer (mCRC) that is incurable or not resectable with curative intent. Participants can proceed to the treatment cohort of the trial if standard of care treatment can be allocated within the timeframes given by the Norwegian national recommendations for the treatment of colorectal cancer. The study duration will be up to 36 months for each participant with treatment duration up to 6 months, and the study visit frequency will be one per participant.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •General conditions:
- •Age 18 or older
- •ECOG performance status 0 or 1
- •Obtained informed consent
- •Acceptable organ function (defined in publicly available protocol)
- •Women of child-bearing potential and men must agree to use highly effective contraception (defined in publicly available protocol)
- •Disease and treatment specific conditions:
- •Histologically confirmed pMMR/MSS adenocarcinoma originating from the colon or rectum
- •Unresectable metastatic disease (not amenable to radical surgery of the cancer disease at the time of study inclusion)
- •Patient has metastatic or primary lesion available for biopsy
- •Patient has measurable or evaluable disease per RECIST (version 1.1)
- •The oxaliplatin-based regimen FOLFOX (+/- antibody) versus the irinotecan-based regimen FOLFIRI (+/- antibody), are evaluated by an experienced physician, independent of inclusion in the trial, to be equally recommended for the participant as standard of care first-line therapy in the treatment of mCRC, following the Norwegian national guideline on the treatment of colorectal cancer (https://www.helsedirektoratet.no/retningslinjer/kreft-i-tykktarm-og-endetarm-handlingsprogram)
- •Patient is eligible for full (100%) chemotherapy doses at first treatment cycle
- •Treatment with chemotherapy can be scheduled within 28 days from referral
排除标准
- •Patient has metastatic MMR deficient/MSI adenocarcinoma
- •Patient is ineligible for full (100%) chemotherapy doses at first treatment cycle
- •Patient is not equally eligible for FOLFOX (+/- antibody) and FOLFIRI (+/- antibody) chemotherapy regimens, according to the Norwegian national guideline on the treatment of colorectal cancer
- •ECOG performance status 2 or worse
- •Pregnancy or planned pregnancy during the study period, due to the risks of drug treatment to a developing foetus
- •Breastfeeding
- •Patients with psychological, geographical, familial or sociological conditions that can prevent compliance with the study protocol
- •Inability to understand study procedures and comply with them, or disorder that compromises the patient's ability to provide informed consent and/or comply with study procedures
- •Patient fulfils any of the contraindications listed in the SmPC of the relevant IMP
- •Treatment cannot be scheduled within 28 days from referral
- •Medical history:
- •Partial or complete dihydropyrimidine dehydrogenase (DPD) deficiency
- •Evidence of CNS metastasis
- •Unresolved toxicities of a previous systemic treatment that, in the opinion of the physician, make the patient unfit for inclusion
- •Antitumoural treatment ≤ 30 days before inclusion. Hormonal substitutive treatment is allowed
- •Preexisting significant cardiovascular disease including uncontrolled/unstable or symptomatic angina, uncontrolled atrial or ventricular arrythmias, LVEF known to be < 40% or symptomatic congestive heart failure
- •Stroke (including TIA) or acute myocardial infarction within 6 months before the first dose of study treatment
- •Clinically significant peripheral sensory neuropathy
- •Recent (<6 months before the start of study treatment) pulmonary embolism, deep vein thrombosis, or another significant thromboembolic event
- •History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis on chest computed tomography (CT)
- •Evidence of previous acute hypersensitivity reaction to any component of the treatment
- •History of any disease that may increase the risks associated with study participation
研究组 & 干预措施
Treatment cohort
FOLFOX or FOLFIRI based on readout from patient-derived tumouroids (via biopsy)
干预措施: FOLFOX or FOLFIRI (Drug)
结局指标
主要结局
Test the feasibility of using a functional precision medicine platform to select oxaliplatin-based versus irinotecan-based chemotherapy regimens for patients with metastatic colorectal cancer.
时间窗: Up to 1 month
Rate of generating valid\* tumouroid response reports per patient included in the trial. \*A valid tumouroid response report for a sample is defined as a fold-change growth in untreated controls of \> 1, registered on day 5, 6, 7 or 8 and normalised with respect to day 0 or 1.
次要结局
- Describe the tumour response to treatment using RECIST v.1.1(Up to 48 months)
- Assess progression free survival(Up to 5 years)
- Assess progression free survival rate(Up to 6 months)
- Assess overall survival(Up to 5 years)
- Toxicity experienced in the trial(Up to 2 years)