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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

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

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

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

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

Learn more about this trial

The p53 Colorectal Cancer Trial

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