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The p53 Colorectal Cancer Trial

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ClinicalTrials.gov Identifier: NCT03149679
Recruitment Status : Terminated (The study was discontinued after the first pre-planned interim analysis due to insufficient response rates.)
First Posted : May 11, 2017
Last Update Posted : January 22, 2021
Sponsor:
Information provided by (Responsible Party):
Haukeland University Hospital

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.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Metastatic Colorectal Cancer Stage IV TP53 Gene Mutation Drug: Cyclophosphamide Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: N/A
Intervention Model: Single Group Assignment
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.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Treatment of Patients With Metastatic Colorectal Cancer Harboring TP53 Mutations With Dose-dense Cyclophosphamide - the p53 Colorectal Cancer Trial
Actual Study Start Date : May 9, 2017
Actual Primary Completion Date : August 7, 2020
Actual Study Completion Date : August 7, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cyclophosphamide arm
Dose dense cyclophosphamide (1800 Mg/m2) administered intravenously every second week.
Drug: Cyclophosphamide
Chemotherapy
Other Name: Sendoxan




Primary Outcome Measures :
  1. Objective response rate (ORR) [ Time Frame: 4 months ]
    Partial response (PR) or complete response (CR) as defined by the RECIST criteria


Secondary Outcome Measures :
  1. Possible molecular markers of therapy response/resistance and survival outcome beyond TP53 mutations will be examined. [ Time Frame: 10 years ]
    Tissue and blood sampling at baseline and whenever treatment is changed

  2. Number of patients with treatment response among patients harboring TP53 mutations belonging to particular mutation subgroups [ Time Frame: 10 years ]
    Tissue and blood sampling at baseline and whenever treatment is changed

  3. Clinical benefit rate (CBR) [ Time Frame: 5 years ]
    Stable disease (SD) >6 months, PR or CR

  4. Recurrence-free and overall survival, compared to historical data [ Time Frame: All patients will be followed for 5 years or until death to record survival outcome ]
    Survival analyses

  5. Safety and tolerability of the study treatment including recording of number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: Every second week during the treatment period from start of treatment, and thereafter every second month for 5 years or until death ]
    Clinical examination and blood samples



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03149679


Locations
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Norway
Haukeland University Hospital
Bergen, Norway, 5021
Sponsors and Collaborators
Haukeland University Hospital
Investigators
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Principal Investigator: Inger Marie Løes, MD PhD Haukeland University Hospital
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Responsible Party: Haukeland University Hospital
ClinicalTrials.gov Identifier: NCT03149679    
Other Study ID Numbers: 2016/1637
First Posted: May 11, 2017    Key Record Dates
Last Update Posted: January 22, 2021
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Haukeland University Hospital:
Cyclophosphamide
Colorectal Cancer Metastatic
TP53 Gene Mutation
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Cyclophosphamide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists