Ex vivo drug sensitivity in metastatic colorectal cancer

An open-label single arm interventional phase 2 study to investigate outcome of individualized treatment based on pharmacogenomic profiling and ex vivo drug sensitivity testing of patient-derived organoids in patients with metastatic colorectal cancer. - EVIDENT

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2020-003395-41-NO

Enrollment

Registered

2020-09-18

Start date

2021-01-15

Completion date

Unknown

Last updated

2024-06-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Metastatic Colorectal Cancer MedDRA version: 21.0 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer System Organ Class: 100000004864

Interventions

Trade Name: Alecensa Product Name: Alectinib Pharmaceutical Form: Capsule, hard Trade Name: Xalkori Product Name: Crizotinib Pharmaceutical Form: Capsule, hard Trade Name: Sprycel Product Name: Dasa

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: Pre-screening Inclusion Criteria 1.Has a histologically-proven locally advanced or metastatic adenocarcinoma from colon or rectum 2.Has received or is receiving systemic treatment for mCRC 3.Has non-resectable metastases and is eligible to undergo a radiological-guided core biopsy from the metasasis. 3.ECOG performance status 0-1 4.Has measurable or evaluable disease (per RECIST v1.1) 5. Is capable of giving signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol Main Study: General Inclusion Criteria 1.Has a histologically-proven locally advanced or metastatic adenocarcinoma from colon or rectum (mCRC) 2.Has received at least two lines of SOC chemotherapy for mCRC 3.Has full combined pharmacogenomic profile (genomic and transcriptomic profile of the patients tumor and ex vivo drug sensitivity testing of PDOs from the patient’s own tumors cells) from which the MTB suggests a treatment with one of the defined targeted anti-cancer therapies provided this study 4.Has measurable or evaluable disease (per RECIST v1.1) 5.ECOG performance status 0-1 6.For orally administered drugs, the patient must be able to swallow and tolerate oral medication and must have no known malabsorption syndrome. 7.Because of the risks of drug treatment to a developing fetus, women of child-bearing potential and men must agree to use adequate contraception in accordance with the respective SmPC and as listed in Appendix 4 for the duration of study participation, and up to 7 months following completion of study therapy. Male study patients, even if surgically sterilized, (i.e. post-vasectomy) must agree to one of the following: practice effective barrier contraception during the entire study treatment period and through 6 months after the last dose of study drug, or completely abstain from sexual intercourse. 8.Has acceptable organ function as defined below. a.Absolute neutrophil count = 1.5/nL b.Hemoglobin > 10 g/dL c.Platelets > 100/nL d.Total bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range 5

Exclusion criteria

Exclusion criteria: Pre-screening: Exclusion Criteria 1.Has other clinically significant medical condition which, in the opinion of the treating physician, makes it undesirable for the patient to participate in the study or which could jeopardize compliance with study requirements. Main Study: General Exclusion Criteria 1. Has ongoing toxicity > CTCAE grade 2, other than peripheral neuropathy, related to anti-tumor treatment that was completed within 4 weeks prior to registration. Patients with ongoing peripheral neuropathy of = CTCAE grade 3 will be excluded. 2. Has received previous treatment with the selected study drug for the same malignancy. 3. Has a tumor with a genomic variant known to confer resistance to an anti-cancer agent available in this study, the patient will not be eligible to receive that agent but will be eligible to receive other drugs available in this study if all inclusion and exclusion criteria are met for that drug. 4. Is receiving any other anti-cancer therapies (cytotoxic, biologic, radiation, or hormonal other than for replacement). Participants may be on warfarin, low molecular weight heparin or direct factor Xa inhibitors, unless such therapies are prohibited by drug-specific exclusion criteria (please consult the corresponding SmPC and Appendix 16 for prohibited medication and contraindication/precautions). 5. Is pregnant or breastfeeding or refuse to practice barrier contraception methods. 6. Has known CNS metastases. 7. Has preexisting cardiac conditions, including uncontrolled or symptomatic angina, uncontrolled atrial or ventricular arrhythmias, or symptomatic congestive heart failure. 8. Has left ventricular ejection fraction (LVEF) known to be < 40%. 9. Has had a stroke (including TIA) or an acute myocardial infarction within 6 months before the first dose of study treatment. 10. Has had acute gastrointestinal bleeding within 1 month of start of treatment 11. Has other clinically significant medical conditions which, in the opinion of the treating physician, makes it undesirable for the patient to participate in the study or which could jeopardize compliance with study requirements. 12. Meets any of the assigned drug contraindications or other drug-specific exclusion criteria as described in the respective SmPC and in Appendix 16.

Design outcomes

Primary

Measure	Time frame
Main Objective: Prescreening: Based on a tumor biopsy, establish a full combined pharmacogenomic profile which can be used to obtain an MTB-nominated treatment provided in the Main Study Main Study: To evaluate the anti-tumor activity, measured as objective response rate (ORR) of MTB-nominated therapies with drugs not approved or implemented in SOC clinical practice for treatment of mCRC - ORR will be assessed for the total population - ORR in each study drug cohort ;Secondary Objective: Pre-screening: To assess the ability to obtain a tumor biopsy and generate full combined pharmacogenomic profile eligible for treatment decisions. To evaluate the combined pharmacogenomic profiling from PDOs to predict clinical outcome of SOC therapy according to guidelines (Observational, in alignment with the translational project ‘SMART Liver’). Main Study: -evaluate progression-free survival, and duration of response of participants receiving an MTB-nominated treatment -evaluate overall survival of participants receiving MTB-nominated anti-cancer therapy - determine the safety and tolerability of the different MTB-nominated treatments - assess the efficacy of MTB-nominated anti-cancer therapy compared to the efficacy of SOC achieved from first-line treatment in each patient - assess the efficacy of an MTB-nominated anticancer therapy compared to the efficacy achieved by the next line(s) of SOC treatment - describe patient-reported quality of life during treatment;Primary end point(s): Pre-screening: Number of patients from whom organoids and a full combined pharmacogenomic profiling were established and eligible for considering an MTB-nominated treatment provided in the Main Study Main Study: Objective response rate (ORR) is a confirmed complete response (CR) or partial response (PR), according to RECIST 1.1 - ORR in the total population - ORR in each study drug cohort;Timepoint(s) of evaluation of this end point: Main Study: Evaluation is planned when all included patients	—

Measure

Time frame

Main Objective: Prescreening: Based on a tumor biopsy, establish a full combined pharmacogenomic profile which can be used to obtain an MTB-nominated treatment provided in the Main Study Main Study: To evaluate the anti-tumor activity, measured as objective response rate (ORR) of MTB-nominated therapies with drugs not approved or implemented in SOC clinical practice for treatment of mCRC - ORR will be assessed for the total population - ORR in each study drug cohort ;Secondary Objective: Pre-screening: To assess the ability to obtain a tumor biopsy and generate full combined pharmacogenomic profile eligible for treatment decisions. To evaluate the combined pharmacogenomic profiling from PDOs to predict clinical outcome of SOC therapy according to guidelines (Observational, in alignment with the translational project ‘SMART Liver’). Main Study: -evaluate progression-free survival, and duration of response of participants receiving an MTB-nominated treatment -evaluate overall survival of participants receiving MTB-nominated anti-cancer therapy - determine the safety and tolerability of the different MTB-nominated treatments - assess the efficacy of MTB-nominated anti-cancer therapy compared to the efficacy of SOC achieved from first-line treatment in each patient - assess the efficacy of an MTB-nominated anticancer therapy compared to the efficacy achieved by the next line(s) of SOC treatment - describe patient-reported quality of life during treatment;Primary end point(s): Pre-screening: Number of patients from whom organoids and a full combined pharmacogenomic profiling were established and eligible for considering an MTB-nominated treatment provided in the Main Study Main Study: Objective response rate (ORR) is a confirmed complete response (CR) or partial response (PR), according to RECIST 1.1 - ORR in the total population - ORR in each study drug cohort;Timepoint(s) of evaluation of this end point: Main Study: Evaluation is planned when all included patients

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Secondary

Measure	Time frame
Secondary end point(s): Pre-screening Number of patients from whom organoids and a full combined pharmacogenomic profile was established and eligible to have suggested - An MTB-nominated treatment provided in the Main Study - An MTB-nominated treatment considered as SOC - An MTB-nominated treatment not considered as SOC and not provided in the Main Study - No MTB-nominated treatment Registered outcome of all systemic SOC oncological treatment; objective response (OR), PFS and DOR OS from start of first-line SOC chemotherapy and OS from start of each line of SOC treatment Main study: PFS, defined as the time from the first dose of the MTB-nominated treatment to the first documented disease progression or death due to any cause, whichever occurs first DOR, defined as the time from the first documented evidence of CR or PR until progressive disease (PD) or death due to any cause, whichever occurs first, in participants demonstrating CR or PR OS, defined as the time from the first dose of MTB-nominated treatment to the date of death from any cause Classify and register adverse vents Assess ORR, DOR, PFS of MTB-nominated treatment and from the previous line of SOC treatment regimen in each patient Assess the number of patients who have a PFS of the MTB-nominated treatment which is >1.3 x PFS of the previous line of therapy Assess ORR, DOR, PFS and of MTB-nominated treatment and form anti-cancer therapy in the next/later lines of SOC treatment in each patient Patient-reported outcome measures ;Timepoint(s) of evaluation of this end point: Main Study: Evaluation is planned when all included patients are followed-up for two years after start of treatment. At this timepoint the pre-screening end points will be evaluated.	—

Measure

Time frame

Secondary end point(s): Pre-screening Number of patients from whom organoids and a full combined pharmacogenomic profile was established and eligible to have suggested - An MTB-nominated treatment provided in the Main Study - An MTB-nominated treatment considered as SOC - An MTB-nominated treatment not considered as SOC and not provided in the Main Study - No MTB-nominated treatment Registered outcome of all systemic SOC oncological treatment; objective response (OR), PFS and DOR OS from start of first-line SOC chemotherapy and OS from start of each line of SOC treatment Main study: PFS, defined as the time from the first dose of the MTB-nominated treatment to the first documented disease progression or death due to any cause, whichever occurs first DOR, defined as the time from the first documented evidence of CR or PR until progressive disease (PD) or death due to any cause, whichever occurs first, in participants demonstrating CR or PR OS, defined as the time from the first dose of MTB-nominated treatment to the date of death from any cause Classify and register adverse vents Assess ORR, DOR, PFS of MTB-nominated treatment and from the previous line of SOC treatment regimen in each patient Assess the number of patients who have a PFS of the MTB-nominated treatment which is >1.3 x PFS of the previous line of therapy Assess ORR, DOR, PFS and of MTB-nominated treatment and form anti-cancer therapy in the next/later lines of SOC treatment in each patient Patient-reported outcome measures ;Timepoint(s) of evaluation of this end point: Main Study: Evaluation is planned when all included patients are followed-up for two years after start of treatment. At this timepoint the pre-screening end points will be evaluated.

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Countries

Norway

Contacts

Public ContactTormod Kyrre Guren

Oslo University Hospital

tormod.kyrre.guren@ous-hf.no+4722934000/94163891

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026