The p53 Colorectal Cancer Trial

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

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.

Study Overview

• Status: Terminated
• Conditions: Colorectal Cancer Metastatic; Colorectal Cancer Stage IV; TP53 Gene Mutation
• Intervention / Treatment: Drug: Cyclophosphamide

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• Norway
  • Bergen, Norway, 5021
    • Haukeland University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cyclophosphamide arm; Dose dense cyclophosphamide (1800 Mg/m2) administered intravenously every second week.	Drug: Cyclophosphamide; Chemotherapy; Other Names: Sendoxan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	Partial response (PR) or complete response (CR) as defined by the RECIST criteria	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Clinical benefit rate (CBR)	Stable disease (SD) >6 months, PR or CR	5 years
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
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

Collaborators and Investigators

• Sponsor: Haukeland University Hospital
• Investigators: Principal Investigator: Inger Marie Løes, MD PhD, Haukeland University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 9, 2017
• Primary Completion (Actual): August 7, 2020
• Study Completion (Actual): August 7, 2020

Study Registration Dates

• First Submitted: March 14, 2017
• First Submitted That Met QC Criteria: May 9, 2017
• First Posted (Actual): May 11, 2017

Study Record Updates

• Last Update Posted (Actual): January 22, 2021
• Last Update Submitted That Met QC Criteria: January 20, 2021
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Cyclophosphamide; Colorectal Cancer Metastatic; TP53 Gene Mutation
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide
• Other Study ID Numbers: 2016/1637

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• 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