Colorectal Cancer Metastatic, Colorectal Cancer Stage IV, TP53 Gene Mutation
Conditions
Keywords
Cyclophosphamide, Colorectal Cancer Metastatic, TP53 Gene Mutation
Brief summary
Single center, open labeled, phase 2 clinical trial, where patients with metastatic colorectal cancer are selected for treatment with dose dense Cyclophosphamide every second week based on TP53 mutation status; i.e. only patients with TP53 mutated tumors may be included in the treatment arm.
Interventions
DRUGCyclophosphamide
Chemotherapy
Sponsors
Haukeland University Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single center, open labeled, phase 2 clinical trial, where patients are selected for treatment based on upfront TP53 mutation status; i.e. only patients with TP53 mutated tumors may be included in the single treatment arm. The informed consent, however needs to be signed prior to a biopsy for TP53 mutation analyses; thus, all patients are formally enrolled in the study prior to tissue collection, and the full population tested will be accounted for despite the fact that only patients with TP53 mutated tumors may enter the single treatment arm.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Metastatic colorectal cancer patients for whom conventional therapy has failed; defined as 2 lines of chemotherapy including oxaliplatin or irinotecan- containing regimens as well as an EGFR inhibitor if applicable. * Tumor lesion suitable for biopsy * Age \>18 years * Clinically or radiologically measurable tumor deposits according to the RECIST criteria * WHO performance status 0-1 * Radiology studies (CT thorax/abdomen/pelvis) and echo cor and ECG must be performed within 28 days prior to registration. * Before patient registration in the trial, written informed consent must be given according to national and local regulations. * Blood test requirements: Neutrophils \> 1.0 e9/L Platelets \> 75 e9/L Bilirubin \< 20 µmol / L. Serum creatinine \< 1.5 x ULN
Exclusion criteria
* Co-morbidity including, but not limited to, impaired renal-, liver or bone marrow function, that based on the assessment of the treating physician, may preclude the use of cyclophosphamide at actual doses. * Known hypersensitivity to the study drug, its metabolites or any excipients in the infusion solution. * Psychological, familial, sociological or geographical condition(s) potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial * Pregnant or lactating patients cannot be included. * Clinical evidence of serious coagulopathy. Prior arterial/venous thrombosis or embolism does not exclude patients from inclusion, unless patient is considered unfit by study oncologist. * Patient not able to give an informed consent or comply with study regulations as deemed by study investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | 4 months | Partial response (PR) or complete response (CR) as defined by the RECIST criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Possible molecular markers of therapy response/resistance and survival outcome beyond TP53 mutations will be examined. | 10 years | Tissue and blood sampling at baseline and whenever treatment is changed |
| Number of patients with treatment response among patients harboring TP53 mutations belonging to particular mutation subgroups | 10 years | Tissue and blood sampling at baseline and whenever treatment is changed |
| Clinical benefit rate (CBR) | 5 years | Stable disease (SD) \>6 months, PR or CR |
| Recurrence-free and overall survival, compared to historical data | All patients will be followed for 5 years or until death to record survival outcome | Survival analyses |
| Safety and tolerability of the study treatment including recording of number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | Every second week during the treatment period from start of treatment, and thereafter every second month for 5 years or until death | Clinical examination and blood samples |
Countries
Norway
Outcome results
None listed