The p53 Colorectal Cancer Trial
Primary Purpose
Colorectal Cancer Metastatic, Colorectal Cancer Stage IV, TP53 Gene Mutation
Status
Terminated
Phase
Phase 2
Locations
Norway
Study Type
Interventional
Intervention
Cyclophosphamide
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer Metastatic focused on measuring Cyclophosphamide, Colorectal Cancer Metastatic, TP53 Gene Mutation
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.
Sites / Locations
- Haukeland University Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Cyclophosphamide arm
Arm Description
Dose dense cyclophosphamide (1800 Mg/m2) administered intravenously every second week.
Outcomes
Primary Outcome Measures
Objective response rate (ORR)
Partial response (PR) or complete response (CR) as defined by the RECIST criteria
Secondary Outcome Measures
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
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
Clinical benefit rate (CBR)
Stable disease (SD) >6 months, PR or CR
Recurrence-free and overall survival, compared to historical data
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
Clinical examination and blood samples
Full Information
NCT ID
NCT03149679
First Posted
March 14, 2017
Last Updated
January 20, 2021
Sponsor
Haukeland University Hospital
1. Study Identification
Unique Protocol Identification Number
NCT03149679
Brief Title
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
2. Study Status
Record Verification Date
February 2020
Overall Recruitment Status
Terminated
Why Stopped
The study was discontinued after the first pre-planned interim analysis due to insufficient response rates.
Study Start Date
May 9, 2017 (Actual)
Primary Completion Date
August 7, 2020 (Actual)
Study Completion Date
August 7, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Haukeland University Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer Metastatic, Colorectal Cancer Stage IV, TP53 Gene Mutation
Keywords
Cyclophosphamide, Colorectal Cancer Metastatic, TP53 Gene Mutation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
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.
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cyclophosphamide arm
Arm Type
Experimental
Arm Description
Dose dense cyclophosphamide (1800 Mg/m2) administered intravenously every second week.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Sendoxan
Intervention Description
Chemotherapy
Primary Outcome Measure Information:
Title
Objective response rate (ORR)
Description
Partial response (PR) or complete response (CR) as defined by the RECIST criteria
Time Frame
4 months
Secondary Outcome Measure Information:
Title
Possible molecular markers of therapy response/resistance and survival outcome beyond TP53 mutations will be examined.
Description
Tissue and blood sampling at baseline and whenever treatment is changed
Time Frame
10 years
Title
Number of patients with treatment response among patients harboring TP53 mutations belonging to particular mutation subgroups
Description
Tissue and blood sampling at baseline and whenever treatment is changed
Time Frame
10 years
Title
Clinical benefit rate (CBR)
Description
Stable disease (SD) >6 months, PR or CR
Time Frame
5 years
Title
Recurrence-free and overall survival, compared to historical data
Description
Survival analyses
Time Frame
All patients will be followed for 5 years or until death to record survival outcome
Title
Safety and tolerability of the study treatment including recording of number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Description
Clinical examination and blood samples
Time Frame
Every second week during the treatment period from start of treatment, and thereafter every second month for 5 years or until death
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Inger Marie Løes, MD PhD
Organizational Affiliation
Haukeland University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Haukeland University Hospital
City
Bergen
ZIP/Postal Code
5021
Country
Norway
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
The p53 Colorectal Cancer Trial
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