The p53 Colorectal Cancer Trial

Phase 2

Terminated

Conditions: Colorectal Cancer Metastatic
Colorectal Cancer Stage IV
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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Cyclophosphamide arm	Cyclophosphamide	Dose dense cyclophosphamide (1800 Mg/m2) administered intravenously every second week.

Primary Outcome Measures

Name	Time	Method
Objective response rate (ORR)	4 months	Partial response (PR) or complete response (CR) as defined by the RECIST criteria

Secondary Outcome Measures

Name	Time	Method
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

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