ALECTINIB for Metastatic colorectal cancer|Colorectal cancer

Inclusion criteria

• {"criterion_text":"- Pre-screeining: Has a histologically-proven locally advanced or metastatic adenocarcinoma from colon or rectum\n- Pre-screening: Has received or is receiving systemic treatment for mCRC\n- Pre-screening: Has non-resectable metastases and eligible to undergo a radiological-guided core biopsy from at least one metastasis\n- Pre-screening: ECOG performance status 0 or 1\n- Pre-screening: Has measurable or evaluable disease (per RECIST v1.1)\n- Pre-screening: 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\n- Main studiy: Has a histologically-proven locally advanced or metastatic adenocarcinoma from colon or rectum (mCRC)\n- Main studiy: Has received at least two lines of SOC chemotherapy for mCRC\n- Main study: 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\n- Main study: Has measurable or evaluable disease (per RECIST v1.1)\n- main Study: ECOG performance status 0 or 1\n- Main study: For orally administered drugs, the participant must be able to swallow and tolerate oral medication and must have no known malabsorption syndrome.\n- Main study: 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\n- Main study: Has acceptable organ function as defined below. However, as noted below (exclusion criteriom 16), drug-specific inclusion/exclusion criteria specified in the Appendix 16/respective SmPC for each agent will take precedence for this and all inclusion criteria:"}

Exclusion criteria

• {"criterion_text":"- Pree-screening: 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.\n- Main study: Has had a stroke (including TIA) or an acute myocardial infarction within 6 months before the first dose of study treatment.\n- Main study: Has had acute gastrointestinal bleeding within 1 month of start of treatment\n- Main study: 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.\n- Main study: Meets any of the assigned drug contraindications or other drug-specific exclusion criteria as described in the respective SmPC and in Appendix 16\n- Main study: Has ongoing toxicity > CTCAE grade 2, other than peripheral neuropathy and alopecia, 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.\n- Main Study: Has received previous treatment with the selected study drug for the same malignancy\n- Main study: 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.\n- Main study: 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).\n- Main study: Is pregnant or breastfeeding or refusing any type of required contraception methods.\n- Main study: Has known CNS metastases.\n- Main study: Has preexisting cardiac conditions, including uncontrolled or symptomatic angina, uncontrolled atrial or ventricular arrhythmias, or symptomatic congestive heart failure.\n- Main study: Has left ventricular ejection fraction (LVEF) known to be < 40%."}

Primary endpoints

• {"endpoint_text":"- Pre-screening: Number of patients from whom organoids and a full combined pharmacogenomic profiling were established and eligible for considering an MTBnominated treatment provided in the Main Study","definition_or_measurement_approach":"Count of patients from whom organoids and a full combined pharmacogenomic profile were established and who were eligible for consideration of an MTB-nominated treatment provided in the Main Study"}
• {"endpoint_text":"- Main study: Objective response rate (ORR) is a confirmed complete response (CR) or partial response (PR).  ORR in the total population.  ORR in each study drug cohort","definition_or_measurement_approach":"ORR defined as confirmed complete response (CR) or partial response (PR); reported for total population and for each study drug cohort"}

Secondary endpoints

• {"endpoint_text":"- 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","definition_or_measurement_approach":"Count of patients with established organoids and full combined pharmacogenomic profile and categorised by type of MTB suggestion (provided in Main Study, considered SOC, not considered SOC/not provided, or no nomination)"}
• {"endpoint_text":"- Pre-screening:  Registered outcome of all systemic SOC oncological treatment; objective response (OR), PFS and DOR.  OS from start of firstline SOC chemotherapy and OS from start of each line of SOC treatment","definition_or_measurement_approach":"Registered outcomes for SOC treatments: objective response, PFS and DOR; OS measured from start of first-line SOC chemotherapy and from start of each SOC line"}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"PFS = time from first dose of MTB-nominated treatment to documented disease progression or death; DOR = time from first documented CR/PR until PD or death"}
• {"endpoint_text":"- Main study: 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.","definition_or_measurement_approach":"OS = time from first dose of MTB-nominated treatment to death from any cause; safety assessed by classifying and recording adverse events"}
• {"endpoint_text":"- Main study:  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.","definition_or_measurement_approach":"Compare ORR, DOR, PFS of MTB-nominated treatment with previous SOC in each patient; count patients with MTB PFS >1.3 × previous line PFS"}
• {"endpoint_text":"- Main study: Assess ORR, DOR, PFS and of MTB-nominated treatment and form anticancer therapy in the next/later lines of SOC treatment in each patient","definition_or_measurement_approach":"Assess ORR, DOR, PFS of MTB-nominated treatment and compare with outcomes from subsequent SOC lines per patient"}
• {"endpoint_text":"- Main study: Patient-reported outcome measures","definition_or_measurement_approach":"Collection of patient-reported outcome measures (details not specified in dataset)"}

Norway

Earliest CTIS Part Ii Submission Date

24-04-2024

Latest Decision Or Authorization Date

16-05-2024

Processing Time Days

22

Number Of Sites

1

Number Of Participants

45

Primary sponsor

Full Name

Oslo University Hospital HF

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Norway