The p53 Colorectal Cancer Trial

NCT03149679 | Terminated Phase 2 DMC

• 1 other identifier: 2016/1637
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Colorectal Cancer Metastatic; Colorectal Cancer Stage IV; TP53 Gene Mutation

Keywords

Cyclophosphamide; Colorectal Cancer Metastatic; TP53 Gene Mutation

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  Partial response (PR) or complete response (CR) as defined by the RECIST criteria

  4 months

Secondary Outcomes (5)

• Possible molecular markers of therapy response/resistance and survival outcome beyond TP53 mutations will be examined.

  10 years

• Number of patients with treatment response among patients harboring TP53 mutations belonging to particular mutation subgroups

  10 years

• Clinical benefit rate (CBR)

  5 years

• Recurrence-free and overall survival, compared to historical data

  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

  Every second week during the treatment period from start of treatment, and thereafter every second month for 5 years or until death

Study Arms (1)

Cyclophosphamide arm

EXPERIMENTAL

Dose dense cyclophosphamide (1800 Mg/m2) administered intravenously every second week.

Drug: Cyclophosphamide

Interventions

Cyclophosphamide DRUG

Chemotherapy

Also known as: Sendoxan

Cyclophosphamide arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• Patient not able to give an informed consent or comply with study regulations as deemed by study investigator.

Sponsors & Collaborators

• Haukeland University Hospital: lead

Study Sites (1)

Haukeland University Hospital

Bergen, 5021, Norway

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Cyclophosphamide

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Inger Marie Løes, MD PhD

  Haukeland University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: March 14, 2017
• First Posted: May 11, 2017
• Study Start: May 9, 2017
• Primary Completion: August 7, 2020
• Study Completion: August 7, 2020
• Last Updated: January 22, 2021

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

NO (1)