Trial Title:
Study to Investigate Outcome of Individualized Treatment in Patients With Metastatic Colorectal Cancer
NCT ID:
NCT05725200
Condition:
Metastatic Colorectal Cancer
Conditions: Official terms:
Colorectal Neoplasms
Gemcitabine
Methotrexate
Pembrolizumab
Trastuzumab
Cetuximab
Everolimus
Venetoclax
Dasatinib
Palbociclib
Crizotinib
Panobinostat
Talazoparib
Idelalisib
Alectinib
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Alectinib
Description:
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.
Arm group label:
Individualized treatment in patients with metastatic colorectal cancer
Intervention type:
Drug
Intervention name:
Cetuximab
Description:
Dosage form, dosage, frequency and duration are to be implemented by study investigators
as described in the current SMPC and package Insert.
Arm group label:
Individualized treatment in patients with metastatic colorectal cancer
Intervention type:
Drug
Intervention name:
Crizotinib
Description:
Dosage form, dosage, frequency and duration are to be implemented by study investigators
as described in the current SMPC and package Insert.
Arm group label:
Individualized treatment in patients with metastatic colorectal cancer
Intervention type:
Drug
Intervention name:
Dasatinib
Description:
Dosage form, dosage, frequency and duration are to be implemented by study investigators
as described in the current SMPC and package Insert.
Arm group label:
Individualized treatment in patients with metastatic colorectal cancer
Intervention type:
Drug
Intervention name:
Everolimus
Description:
Dosage form, dosage, frequency and duration are described in the current SMPC and package
Insert.
Arm group label:
Individualized treatment in patients with metastatic colorectal cancer
Intervention type:
Drug
Intervention name:
Encorafenib
Description:
Dosage form, dosage, frequency and duration are to be implemented by study investigators
as described in the current SMPC and package Insert.
Arm group label:
Individualized treatment in patients with metastatic colorectal cancer
Intervention type:
Drug
Intervention name:
Gemcitabine
Description:
Dosage form, dosage, frequency and duration are described in the current SMPC and package
Insert.
Arm group label:
Individualized treatment in patients with metastatic colorectal cancer
Intervention type:
Drug
Intervention name:
Idelalisib
Description:
Dosage form, dosage, frequency and duration are to be implemented by study investigators
as described in the current SMPC and package Insert.
Arm group label:
Individualized treatment in patients with metastatic colorectal cancer
Intervention type:
Drug
Intervention name:
Larotrectinib
Description:
Dosage form, dosage, frequency and duration are to be implemented by study investigators
as described in the current SMPC and package Insert.
Arm group label:
Individualized treatment in patients with metastatic colorectal cancer
Intervention type:
Drug
Intervention name:
Methotrexate
Description:
Dosage form, dosage, frequency and duration are to be implemented by study investigators
as described in the current SMPC and package Insert.
Arm group label:
Individualized treatment in patients with metastatic colorectal cancer
Intervention type:
Drug
Intervention name:
Palbociclib
Description:
Dosage form, dosage, frequency and duration are to be implemented by study investigators
as described in the current SMPC and package Insert.
Arm group label:
Individualized treatment in patients with metastatic colorectal cancer
Intervention type:
Drug
Intervention name:
Panobinostat
Description:
Dosage form, dosage, frequency and duration are to be implemented by study investigators
as described in the current SMPC and package Insert.
Arm group label:
Individualized treatment in patients with metastatic colorectal cancer
Intervention type:
Drug
Intervention name:
Pembrolizumab
Description:
Dosage form, dosage, frequency and duration are to be implemented by study investigators
as described in the current SMPC and package Insert.
Arm group label:
Individualized treatment in patients with metastatic colorectal cancer
Intervention type:
Drug
Intervention name:
Petrozumab
Description:
Dosage form, dosage, frequency and duration are to be implemented by study investigators
as described in the current SMPC and package Insert.
Arm group label:
Individualized treatment in patients with metastatic colorectal cancer
Intervention type:
Drug
Intervention name:
Trastuzumab
Description:
Dosage form, dosage, frequency and duration are to be implemented by study investigators
as described in the current SMPC and package Insert.
Arm group label:
Individualized treatment in patients with metastatic colorectal cancer
Intervention type:
Drug
Intervention name:
Talazoparib
Description:
Dosage form, dosage, frequency and duration are to be implemented by study investigators
as described in the current SMPC and package Insert.
Arm group label:
Individualized treatment in patients with metastatic colorectal cancer
Intervention type:
Drug
Intervention name:
Venetoclax
Description:
Dosage form, dosage, frequency and duration are to be implemented by study investigators
as described in the current SMPC and package Insert.
Arm group label:
Individualized treatment in patients with 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.
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.
Criteria for eligibility:
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/exclusion criteria specified in the Appendix
16/respective SmPC for each agent will take precedence for this and all inclusion
criteria:
1. Absolute neutrophil count ≥ 1.5/nL (nL = nano Litre)
2. Hemoglobin > 10 g/dL
3. Platelets > 100/nL
4. Total bilirubin < 1.5 x institutional upper limit of normal (ULN)
5. 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)
6. Calculated or measured creatinine clearance ≥ 50 mL/min/1.73 m2
Exclusion Criteria:
1. 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.
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 refusing any type of required contraception methods.
6. Has known Central Nervous System (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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Oslo University Hospital
Address:
City:
Oslo
Zip:
0379
Country:
Norway
Status:
Recruiting
Contact:
Last name:
Tormod K Guren, MDPhD
Start date:
September 27, 2022
Completion date:
December 31, 2040
Lead sponsor:
Agency:
Oslo University Hospital
Agency class:
Other
Source:
Oslo University Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05725200