Metastatic Colorectal Cancer
Conditions
Brief 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.
Detailed description
The purpose of the study is to evaluate individualized systemic anti-cancer treatment of metastatic colorectal cancer (mCRC), selected by a combined pharmacogenomic drug sensitivity profile with a molecular profiling of the tumor tissue and an ex vivo drug sensitivity testing of patient-derived organoids (PDOs). The combined pharmacogenomic drug sensitivity profile will be provided by Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital (OUS) and will be a result of either i) a pre-screening performed in this study or ii) from previous biomarker analyses and drug sensitivity testing of PDOs as part of an ongoing translational research project at Dept. of Molecular Oncology. The combined pharmacogenomic profile will be interpreted by an institutional multidisciplinary tumor board (MTB), and in cases where the MTB strongly suggests that the patient will benefit from one of the interventions offered by this study, the patient will be invited to participate. No formal hypotheses testing will be performed in the study, but it aims to show that it is feasible, in an unselected population of patients with mCRC, to select patients for individualized therapy based on a broad genomic and transcriptomic profiling and ex vivo drug sensitivity testing of cultured PDOs from the patient's own tumor cells, and to provide evidence that a combined pharmacogenomic profile can predict objective antitumor responses to systemic anticancer therapies, including drugs not approved for treatment of patients with mCRC, in the setting of third-line therapy or in later lines. In addition, this study will be part of several translational research projects at the Department of Molecular Oncology.
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
Dosage form, dosage, frequency and duration are to be implemented by study investigators as described in the current SMPC and package Insert.
DRUGCrizotinib
Dosage form, dosage, frequency and duration are to be implemented by study investigators as described in the current SMPC and package Insert.
DRUGDasatinib
Dosage form, dosage, frequency and duration are to be implemented by study investigators as described in the current SMPC and package Insert.
DRUGEverolimus
Dosage form, dosage, frequency and duration are described in the current SMPC and package Insert.
DRUGEncorafenib
Dosage form, dosage, frequency and duration are to be implemented by study investigators as described in the current SMPC and package Insert.
DRUGGemcitabine
Dosage form, dosage, frequency and duration are described in the current SMPC and package Insert.
DRUGIdelalisib
Dosage form, dosage, frequency and duration are to be implemented by study investigators as described in the current SMPC and package Insert.
DRUGLarotrectinib
Dosage form, dosage, frequency and duration are to be implemented by study investigators as described in the current SMPC and package Insert.
DRUGMethotrexate
Dosage form, dosage, frequency and duration are to be implemented by study investigators as described in the current SMPC and package Insert.
DRUGPalbociclib
Dosage form, dosage, frequency and duration are to be implemented by study investigators as described in the current SMPC and package Insert.
DRUGPanobinostat
Dosage form, dosage, frequency and duration are to be implemented by study investigators as described in the current SMPC and package Insert.
DRUGPembrolizumab
Dosage form, dosage, frequency and duration are to be implemented by study investigators as described in the current SMPC and package Insert.
DRUGPetrozumab
Dosage form, dosage, frequency and duration are to be implemented by study investigators as described in the current SMPC and package Insert.
DRUGTrastuzumab
Dosage form, dosage, frequency and duration are to be implemented by study investigators as described in the current SMPC and package Insert.
DRUGTalazoparib
Dosage form, dosage, frequency and duration are to be implemented by study investigators as described in the current SMPC and package Insert.
DRUGVenetoclax
Dosage form, dosage, frequency and duration are to be implemented by study investigators as described in the current SMPC and package Insert.
Sponsors
Oslo University Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Pre-screening: Inclusion Criteria: * 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
Exclusion criteria
* 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: 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 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. 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 or 1 6. For orally administered drugs, the participant 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. However, as noted below (exclusion criterion 16), drug-specific inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pre-Screening: Obtain a combined pharmacogenomic profile which can be used to provide a MTB-nominated treatment | In average of 3 months | Number of participants that obtain a full combined pharmacogenomic profile which can be used to provide an MTB-nominated treatment 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 standard of care (SOC) for treatment of mCRC. | Through study completion, in average 6 months | Number of patients who achieve objective response according RECIST 1.1 in the total study population and each study drug cohort of MTB-nominated therapies with drugs not approved or implemented SOC for treatment of mCRC. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Main Study: Overall survival (OS) | Through study completion, approximately 6 months | OS of participants receiving MTB-nominated anti-cancer therapy, defined as the time from first dose of MTB-nominated treatment to date of death from any cause by calculation of number of days, weeks or years. |
| Main Study: Safety and tolerability of the different MTB-nominated treatments | Through study completion, approximately 6 months | Register adverse events (AE) in accordance with CTCAE v 5.1 |
| Main Study: Objective response of an MTB-nominated anti-cancer therapy compared to objective response to the prior line(s) SOC treatment. | Through study completion, approximately 6 months | Number of patients who achieve objective response according to RECIST 1.1 from anti-cancer therapy (SOC) in prior lines. |
| Pre-Screening: To obtain a full combined pharmacogenomic profile from a tumor biopsy that is eligible for treatment decisions in a standard oncology practice. | Through study completion, approximately 4 years | Pre-Screening: Number of participants who achieve a full combined pharmacogenomic profile eligible for treatment decisions either by * 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 suggested |
| Main study: Objective response of an MTB-nominated anti-cancer therapy compared to objective response to the next line(s) SOC treatment. | Through study completion, approximately 6 months. | Number of patients who achieve objective response according to RECIST 1.1 from receiving anti-cancer therapy in the next/later lines. |
| Main study: Efficacy of an MTB-nominated anti-cancer therapy compared to the efficacy achieved by the next line(s) of SOC treatment. | Through study completion, approximately 6 months. | DOR and PFS by RECIST 1.1 of participants receiving an MTB-nominated treatment and from anti-cancer therapy in the next/later lines of SOC treatment in each patient, by calculation of number of days, weeks or years. |
| Main study: Patient-reported outcome measures. | Through study completion, approximately 6 months. | Describe patient-reported quality of life during the MTB-nominated treatment, registered by EORTC Quality of Life Questionnaire (QLQ)-C30 questionnaire. The EORTC QLQ-C30 questionnaire consisted of 30 questions generating five functional scores (physical, role, cognitive, emotional, and social); a global health status/global quality of life scale score; three symptom scale scores (fatigue, pain, and nausea and vomiting); and six stand alone one-item scores that capture additional symptoms (dyspnea, appetite loss, sleep disturbance, constipation, and diarrhea) and perceived financial burden. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning. |
| Main Study: Efficacy of MTB-nominated anti-cancer therapy compared to the efficacy of prior lines SOC treatment. | Through study completion, approximately 6 months. | DOR and PFS by RECIST 1.1 of participants receiving an MTB-nominated treatment and from anti-cancer therapy received in prior lines of SOC in each patient, by calculation of number of days, weeks or years. |
| Main Study: Progression-free survival (PFS) and duration of response (DOR) | Through study completion, approximately 6 months | Progression-free survival (PFS) and duration of response (DOR) by RECIST 1.1, of participants receiving an MTB-nominated anti-cancer therapy, by calculation of number of days, weeks or years. |
Countries
Norway
Contacts
Primary ContactTormod K Guren, MDPhD
Outcome results
None listed