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Liver MetastasisPhase 1/2DECITNCT02316028

Phase I:Decitabine by Hepatic Arterial Infusion(HAI) in Unresectable Liver Metastases Colorectal Cancer (CRC)

A Phase 1/2 study testing Decitabine in people with Liver Metastasis and Colorectal Cancer, run by Universitair Ziekenhuis Brussel at 2 sites in Belgium.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Despite the advances in the medical treatment of unresectable liver metastases from colorectal cancer there is currently no curative treatment option available for these patients. Decitabine is a cytidine analog with proven anti-neoplastic activity in patients with acute myeloid leukemia and myelodysplastic syndromes. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Liver Metastasis, Colorectal Cancer
What is being tested?
Decitabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
2 sitesBelgium
Study dates
Mar 2014to Jul 2017
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histological documentation of colorectal adenocarcinoma CRC stage IV with predominant unresectable liver metastases and at least one measurable metastatic liver lesion
  • Performance status WHO criteria of < 2.
  • Laboratory values: absolute neutrophil count (ANC) count > 1500 /mm³, Platelet count > 100 000 /mm³, Lymphocytes > 800 /mm³, Serum creatinine < 2.0 mg/dl or creatinine clearance >40 ml/min, Serum bilirubin < 2.0 mg/dl
  • Progressive disease following standard of care palliative systemic chemotherapy
  • able to give written informed consent.

Who cannot join

  • No prior radiotherapy to all target liver lesions
  • No previous history of gastric or hepatobiliary surgery (except for simple cholecystectomy, No concurrent liver disease or other serious medical disease or condition
  • No concomitant use of other investigational drugs.
  • No pre-existing neuropathy with a severity of > grade 1 in the WHO toxicity scale.
  • No previous or concurrent malignancies except for adequately treated in situ carcinoma of the cervix uteri, basal or squamous cell carcinoma of the skin or any other malignancy given potentially curative treatment more than 5 years before study entry
  • No pregnant or breast-feeding female patients, use of an effective contraceptive if the risk of conception exists during study treatment.
  • No candidate for the resection of all CRC metastases with curative intent.

Trial locations and contacts

2 sites in 1 country.

Belgium2 sites

  • UZ Brussel

    Brussels, 1090

  • UZ Brussel

    Jette, Brabant, 1090

Other trials in Belgium

About this study

Official title: A Phase I Clinical Trial on Decitabine (5-aza-2'-Deoxycytidine) Administered by Hepatic Arterial Infusion in Patients With Unresectable Liver-predominant Metastases From Colorectal Cancer

Despite the advances in the medical treatment of unresectable liver metastases from colorectal cancer there is currently no curative treatment option available for these patients. Decitabine is a cytidine analog with proven anti-neoplastic activity in patients with acute myeloid leukemia and myelodysplastic syndromes. Decitabine causes demethylation of the DNA strands of replicating cells. Hereby decitabine treatment demethylates the promoter regions of tumor suppressor- and cancer testis antigen encoding genes leading to expression of these genes by the cancer cells. The hepatic arterial route for administration of cytotoxic drugs has been widely explored in treatment of colorectal cancer liver metastases because these metastases depend for their blood flow from this artery (as opposed to the normal liver tissue that is mainly dependent from the portal vein). By investigating the administration of decitabine by hepatic arterial infusion the investigators intend to explore the potential advantage of minimizing the systemic exposure (and toxicity) and maximizing the concentration of decitabine within the liver metastasis. The primary objective of this phase I will be to establish the recommended dose for decitabine by HAI for further use in phase II trials. The most important secondary objective will be to document the effect of decitabine by HAI on the expression of cancer testis antigens by the colorectal cancer cells, serving as a reference for potential further exploration of decitabine by HAI in combination with cancer immunotherapy

Read the detailed description

This clinical trial will recruit eligible patients diagnosed with unresectable liver-predominant colorectal cancer metastases who have experience progression of their disease following standard of care treatment.

Unless patients already dispose of a hepatic arterial catheter, they will undergo placement of a permanent hepatic artery catheter (by laparoscopic surgery). During this surgical procedure a biopsy will be made of the colorectal cancer liver metastasis.

Decitabine will be administered as a daily 1-hour IV infusion on 5 consecutive days, every 4weeks.

Two weeks after the first day of administration of decitabine, a CT-guided biopsy a liver metastasis will be performed in order to obtain tumor tissue for histopathological analysis and DNA/RNA extraction for the purposes of methylation specific Polymerase Chain Reaction (PCR) and reverse transcriptase PCR for assessment of demethylation and expression of cancer-testis antigen encoding genes.

Blood samples for collection of "cell-free DNA" and White Blood Cell (WBC ) for the purpose of DNA/RNA extraction and analysis by methylation specific PCR and reverse transcriptase PCR for assessment of demethylation and expression of cancer-testis antigen encoding genes will be obtained weekly after decitabine treatment.

The dose of decitabine will be escalated in subsequent patient cohorts enrolled to this phase I trial (see rules for dose escalation).

Study treatment will be continued until unacceptable toxicity, progressive disease or patient refusal.

Being tested
Decitabine
Keywords
decitabine, colorectal cancer, hepatic arterial infusion
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DecitabineDrug

    Also called Dacogen

    administration of decitabine by hepatic arterial infusion

    • Accrual of patients and dosing of decitabine will be guided by a traditional 3+3 design using an accelerated titration for the first three dose levels.
    • Proposed dose levels:
    1. 10 mg/m2 per course
    2. 15 mg/m2 per course
    3. 20 mg/m2 per course
Study groups in NCT02316028
Study groupRoleWhat they receive
decitabineExperimentaladministration of decitabine by hepatic arterial infusion * Accrual of patients and dosing of decitabine will be guided by a traditional 3+3 design using an accelerated titration for the first three dose levels. * Proposed dose levels: 1. 10 mg/m2 per course 2. 15 mg/m2 per course 3. 20 mg/m2 per course
Receives: Drug: Decitabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. toxicity of escalating doses of decitabine administered by HAI

    : to establish the recommended dose of decitabine administered by hepatic arterial infusion in patients with unresectable liver-predominant metastases from colorectal cancer

    Measured: 2years

Secondary outcomes (5)

  1. overall survival

    overall survival

    Measured: 5years

  2. progression free survival

    progression free survival

    Measured: 5 years

  3. best objective tumor response

    Best objective tumor response (BOR) per Response Evaluation Criteria in Solid Tumors (RECIST ), version 1.1

    Measured: 5 years

  4. measuring Global DNA methylation of tumoral DNA

    Determine the methylation status of the promoter region and messenger ribonucleic acid (mRNA) expression of cancer-testis antigens in pré- and post treatment biopsies of colorectal cancer liver metastases

    Measured: 2years

  5. measuring Global DNA methylation of cell free DNA

    Determine the ratio of demethylated versus methylated DNA corresponding to the promoter region of cancer-testis antigen encoding genes on the circulating free DNA (cfDNA) in venous blood prior to and following the administration of decitabine by HAI

    Measured: 2years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Dec 2014 (estimated)
  2. Study startMar 2014
  3. Primary completionDec 2016
  4. Study completionJul 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02316028
Sponsor's protocol ID
UZB-BN-2013-002
Acronym
DECIT
Status last verified
Oct 2017
First submitted
3 Dec 2014
Last updated
27 Oct 2017
Results posted
No
Data monitoring committee
No

Publications

  • Jansen YJL, Verset G, Schats K, Van Dam PJ, Seremet T, Kockx M, Van Laethem JB, Neyns B. Phase I clinical trial of decitabine (5-aza-2'-deoxycytidine) administered by hepatic arterial infusion in patients with unresectable liver-predominant metastases. ESMO Open. 2019 Mar 5;4(2):e000464. doi: 10.1136/esmoopen-2018-000464. eCollection 2019.

    PubMed 30962963

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Decitabine in people with Liver Metastasis and Colorectal Cancer, run by Universitair Ziekenhuis Brussel at 2 sites in Belgium.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

toxicity of escalating doses of decitabine administered by HAI (time frame: 2years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02316028, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2017.

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