Treatment of Patients With Metastatic Colorectal Cancer Harboring TP53 Mutations With Dose-dense Cyclophosphamide - the p53 Colorectal Cancer Trial

Haukeland University Hospital1 site in 1 country12 target enrollmentMay 9, 2017

ConditionsColorectal Cancer Metastatic Colorectal Cancer Stage IV TP53 Gene Mutation

InterventionsCyclophosphamide

DrugsCyclophosphamide

Overview

Phase: Phase 2
Intervention: Cyclophosphamide
Conditions: Colorectal Cancer Metastatic
Sponsor: Haukeland University Hospital
Enrollment: 12
Locations: 1
Primary Endpoint: Objective response rate (ORR)
Status: Terminated
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

May 9, 2017

End Date

August 7, 2020

Last Updated

5 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Haukeland University Hospital

Responsible Party

Sponsor

Eligibility Criteria

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.

Arms & Interventions

Cyclophosphamide arm

Dose dense cyclophosphamide (1800 Mg/m2) administered intravenously every second week.

Intervention: Cyclophosphamide

Outcomes

Primary Outcomes

Objective response rate (ORR)

Time Frame: 4 months

Partial response (PR) or complete response (CR) as defined by the RECIST criteria

Secondary Outcomes

Possible molecular markers of therapy response/resistance and survival outcome beyond TP53 mutations will be examined.(10 years)
Number of patients with treatment response among patients harboring TP53 mutations belonging to particular mutation subgroups(10 years)
Clinical benefit rate (CBR)(5 years)
Recurrence-free and overall survival, compared to historical data(All patients will be followed for 5 years or until death to record survival outcome)
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)