Clinical trial NCT03149679: The p53 Colorectal Cancer Trial
Official title: Treatment of Patients With Metastatic Colorectal Cancer Harboring TP53 Mutations With Dose-dense Cyclophosphamide - the p53 Colorectal Cancer Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Colorectal Cancer Metastatic
Colorectal Cancer Stage IV
TP53 Gene Mutation
Keywords: Cyclophosphamide
Colorectal Cancer Metastatic
TP53 Gene Mutation
Lead sponsor: Haukeland University Hospital
Sponsor class: OTHER
First posted: 2017-05-11
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: 4 months
Secondary outcomes:
measure: Possible molecular markers of therapy response/resistance and survival outcome beyond TP53 mutations will be examined.
timeFrame: 10 years
measure: Number of patients with treatment response among patients harboring TP53 mutations belonging to particular mutation subgroups
timeFrame: 10 years
measure: Clinical benefit rate (CBR)
timeFrame: 5 years
measure: Recurrence-free and overall survival, compared to historical data
timeFrame: All patients will be followed for 5 years or until death to record survival outcome
measure: Safety and tolerability of the study treatment including recording of number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: Every second week during the treatment period from start of treatment, and thereafter every second month for 5 years or until death
Other outcomes:
Locations:
city: Bergen
country: Norway
facility: Haukeland University Hospital
Study officials:
affiliation: Haukeland University Hospital
name: Inger Marie Løes, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: