RecruitingPhase 2NCT05725200

Study to Investigate Outcome of Individualized Treatment in Patients With Metastatic Colorectal Cancer

Study to Investigate Outcome of Individualized Treatment Based on Pharmacogenomic Profiling & Ex Vivo Drug Sensitivity Testing of Patient-derived Organoids in Patients With Metastatic Colorectal Cancer

Sponsor

Oslo University Hospital

Enrollment

40 participants

Start Date

Sep 27, 2022

Study Type

INTERVENTIONAL

Conditions

Metastatic Colorectal Cancer

Summary

The purpose of the study is to investigate the effect and side effects of personalized cancer treatment in patients with metastatic colorectal cancer (bowel cancer). All patients included must have metastatic bowel cancer and receive or have received at least two lines of standard chemotherapy. The cancer must not be available for surgery with curative intent.

Eligibility

Min Age: 18 Years

Inclusion Criteria20

Pre-screening:
Has a histologically-proven locally advanced or metastatic adenocarcinoma from colon or rectum
Has received or is receiving systemic treatment for mCRC
Has non-resectable metastases and eligible to undergo a radiological-guided core biopsy from at least one metastasis
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Has measurable or evaluable disease (per RECIST v1.1)
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
Has a histologically-proven locally advanced or metastatic adenocarcinoma from colon or rectum (mCRC)
Has received at least two lines of SOC chemotherapy for mCRC Note: 1) For patients who develop a metastatic relapse \< 6 months after completed total neo-adjuvant treatment in conjunction with a metastasectomy, this treatment will be considered as one line (e.g. first-line) chemotherapy. 2) Patients with the gene RAS wild-type tumors should have received or have been offered and refused prior treatment with antibodies against epidermal growth factor receptor (EGFR) (e.g. in combination with prior lines of chemotherapy) unless it was contraindicated due to underlying conditions or the tumor contains molecular alterations suggested to provide primary resistance to EGFR-targeted therapy.
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
Has measurable or evaluable disease (per RECIST v1.1)
ECOG performance status 0 or 1
For orally administered drugs, the participant must be able to swallow and tolerate oral medication and must have no known malabsorption syndrome.
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.
Absolute neutrophil count ≥ 1.5/nL (nL = nano Litre)
Hemoglobin \> 10 g/dL
Platelets \> 100/nL
Total bilirubin \< 1.5 x institutional upper limit of normal (ULN)
Aspartate aminotransferase AST (SGOT) and alanine aminotransferase ALT(SGPT) \< 2.5 x institutional upper limit of normal (ULN) (or \< 5 x ULN in patients with known hepatic metastases)
Calculated or measured creatinine clearance ≥ 50 mL/min/1.73 m2

Exclusion Criteria11

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.
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.
Has received previous treatment with the selected study drug for the same malignancy.
Is pregnant or breastfeeding or refusing any type of required contraception methods.
Has known Central Nervous System (CNS) metastases.
Has preexisting cardiac conditions, including uncontrolled or symptomatic angina, uncontrolled atrial or ventricular arrhythmias, or symptomatic congestive heart failure.
Has left ventricular ejection fraction (LVEF) known to be \< 40%.
Has had a stroke (including TIA) or an acute myocardial infarction within 6 months before the first dose of study treatment.
Has had acute gastrointestinal bleeding within 1 month of start of treatment
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.

Interventions

DRUGAlectinib

Dosage form, dosage, frequency and duration are to be implemented by study investigators as described in the current Summary of Product Characteristics (SMPC) and package Insert.

DRUGCetuximab