The p53 Colorectal Cancer Trial

Colorectal Cancer Metastatic Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03149679
• Other study ID #: 2016/1637
• Status: Terminated
• Phase: Phase 2
• Start date: May 9, 2017
• Est. completion date: August 7, 2020

Study information

• Verified date: February 2020
• Source: Haukeland University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 information / eligibility

• Status: Terminated
• Enrollment: 12
• Est. completion date: August 7, 2020
• Est. primary completion date: August 7, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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.

Related Conditions & MeSH terms

• Colorectal Cancer Metastatic
• Colorectal Cancer Stage IV
• Colorectal Neoplasms
• TP53 Gene Mutation

Intervention

Drug:
• Cyclophosphamide
Chemotherapy

Locations

Country	Name	City	State
Norway	Haukeland University Hospital	Bergen

Sponsors (1)

Lead Sponsor	Collaborator
Haukeland University Hospital

Country where clinical trial is conducted

Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate (ORR)	Partial response (PR) or complete response (CR) as defined by the RECIST criteria	4 months
Secondary	Possible molecular markers of therapy response/resistance and survival outcome beyond TP53 mutations will be examined.	Tissue and blood sampling at baseline and whenever treatment is changed	10 years
Secondary	Number of patients with treatment response among patients harboring TP53 mutations belonging to particular mutation subgroups	Tissue and blood sampling at baseline and whenever treatment is changed	10 years
Secondary	Clinical benefit rate (CBR)	Stable disease (SD) >6 months, PR or CR	5 years
Secondary	Recurrence-free and overall survival, compared to historical data	Survival analyses	All patients will be followed for 5 years or until death to record survival outcome
Secondary	Safety and tolerability of the study treatment including recording of number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Clinical examination and blood samples	Every second week during the treatment period from start of treatment, and thereafter every second month for 5 years or until death