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Colon CancerEarly Phase 1ZAK-0NCT02774512

Predictive Biomarkers of Biological Activity and Efficacy of Nilotinib on ZAK Target in Non-metastatic Colon Cancer

A Early Phase 1 study testing Nilotinib in people with Colon Cancer, run by Institut Bergonié at 1 site in France.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This is a monocentric prospective non randomized phase 0 clinical trial targeting patients with colon cancer for whom an upfront surgery has been advised by the pluridisciplinary team. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colon Cancer
What is being tested?
Nilotinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteFrance
Study dates
May 2016to Nov 2017
Phase
Early Phase 1
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

  • Written informed consent signed prior any study-related procedures.
  • Histological diagnosis of colon cancer.
  • Performance status ECOG 0, 1, or 2.
  • Physical status score ASA 1 or 2.
  • Patient without metastasis.
  • No previous anti-cancer treatment for colon cancer.
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  • Age ≥ 18.
  • Preoperative imaging: thorax-abdominal-pelvis CT scan within 2 months.
  • Colonoscopy and biopsies to determine ZAK-0 expression level.
  • Scheduled beginning of the treatment 7 days before surgical procedure.
  • Adequate end organ function as defined by:
  • 11.1. total bilirubin < 1.5 x ULN,1 11.2. SGOT and SGPT < 2.5 x ULN, 11.3. creatinine < 1.5 x ULN, 11.4. Serum amylase and lipase ≤ 1.5 x ULN, 11.5. Alkaline phosphatase ≤ 2.5 x ULN unless considered tumor related.
  • Female patients of childbearing potential must have a negative serum pregnancy test within 7 days before initiation of study drug. Women of child-bearing potential must agree to use adequate contraception, according to investigator's instructions.
  • Effective contraception must be in place :
  • During the treatment with nilotinib
  • Until 2 weeks after the end of treatment.
  • Patients must have the following laboratory values (≥ LLN (lower limit of normal) or corrected to within normal limits with supplements prior to the first dose of study medication): 13.1. Potassium ≥ LLN, 13.2. Magnesium ≥ LLN, 13.3. Phosphorus, ≥ LLN, 13.4. Total calcium (corrected for serum albumin) ≥ LLN.
  • Patients with a French social security in compliance with the French law relating to biomedical research (Article L.1121-11 of French Public Health Code).

Who cannot join

  • Rectal tumors (up to 15 cm from the anus)
  • Any metastasis.
  • Performance status ECOG ≥ 3.
  • Physical status score ASA ≥ 3.
  • Impaired cardiac function including any one of the following:
  • 5.1. LVEF < 45% or below the institutional lower limit of the normal range (whichever is higher) as determined by locally read echocardiogram. 5.2. Inability to determine the QT interval on ECG. 5.3. Complete left bundle branch block. 5.4. Use of a ventricular-paced pacemaker. 5.5. Congenital long QT syndrome or a known family history of long QT syndrome. 5.6. History of or presence of clinically significant ventricular or atrial tachyarrhythmias. 5.7. Clinically significant resting bradycardia (< 50 beats per minute). 5.8. QTc > 450 msec on the average of three serial baseline ECG (using the QTcF formula) as determined by central reading. If QTcF > 450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient rescreened for QTc. 5.9. History of clinically documented myocardial infarction. 5.10. History of unstable angina (during the last 12 months). 5.11. Other clinically significant heart disease (e.g. congestive heart failure or uncontrolled hypertension).
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  • Severe or uncontrolled medical conditions (i.e. uncontrolled diabetes, active or uncontrolled infection).
  • History of significant congenital or acquired bleeding disorder unrelated to cancer.
  • Major surgery within 4 weeks prior to Day 1 of study or who have not recovered from prior surgery.
  • History of non-compliance to medical regimens or inability to grant consent.
  • Use of therapeutic coumarin derivatives (i.e., warfarin, acenocoumarol, phenprocoumon).
  • Patients actively receiving therapy with strong CYP3A4 inhibitors (e.g., erythromycin, ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, ritonavir, mibefradil) and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug.
  • Patients actively receiving therapy with strong CYP3A4 inducers (e.g., dexamthasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbitol, St. John's Wort) and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug.
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection, or gastric bypass surgery).
  • History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis.
  • Acute or chronic liver, pancreatic or severe renal disease considered unrelated to disease.
  • Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug.
  • Patients who are: (a) pregnant, (b) breast feeding, (c) of childbearing potential without a negative pregnancy test prior to baseline and (d) female of childbearing potential unwilling to use contraceptive precautions throughout the trial and until two weeks after the end of treatment (post-menopausal women must be amenorrheic for at least 12 months to be considered of nonchildbearing potential). Contra-indication to nilotinib administration.
  • Previous or current malignancies other than colon cancer within the last 5 years, with the exception of adequately treated basal cell or squamous cell carcinoma of the skin.
  • Emergency surgeries, including occlusion.
  • Previous enrolment in the present study.
  • Patient unable to follow and comply with the study procedures because of any geographical, social or psychological reasons.

Trial locations and contacts

1 site in 1 country.

France1 site

  • Institut Bergonié

    Bordeaux, 33076

Other trials in France

About this study

Official title: Phase 0 Study Aiming at Identifying Predictive Biomarkers of Biological Activity and Efficacy of Nilotinib on ZAK Target in Non-metastatic Colon Cancer

This is a monocentric prospective non randomized phase 0 clinical trial targeting patients with colon cancer for whom an upfront surgery has been advised by the pluridisciplinary team.

Read the detailed description

This is a monocentric prospective non randomized phase 0 clinical trial targeting patients with colon cancer for whom an upfront surgery has been advised by the pluridisciplinary team. The surgical management should not be changed or delayed. The patient is seen in consultation by one of the two surgeons. The patient receives information and consents to participate to the study. A specific colonoscopy is performed in order to take biopsy for biological studies. According to the expression level of ZAK-0, the patient is included in the corresponding arm: ZAK-0 expressor or ZAK-0 non-expressor. Then the patient receives nilotinib orally at the dose of 800 mg/day (400 mg twice a day) for 7 days. The patient is scheduled for surgery the morning after the last take of the nilotinib (12 hours). When the colectomy is performed, the surgeon collects different tumoral samples which are immediately delivered to the laboratory. There are no additional changes in the clinical follow up.

Conditions
Colon Cancer
Being tested
Nilotinib
Medical subject headings
Colonic Neoplasms

What participants receive

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

  • NilotinibDrug

    Each patient will receive nilotinib 800 mg/day every day for 7 days. Study treatment will be taken twice a day (400 mg - 2 capsules) by oral route with an interval of approximately 12 hours between two doses and should not be taken with food. The entire capsule should be swallowed with water. No food should be consumed for 2 hours before taking the drug and for at least 1 hour after it.

Study groups in NCT02774512
Study groupRoleWhat they receive
NilotinibExperimentalA specific colonoscopy is performed in order to take biopsy for biological studies to determine the ZAK-0 expression status. Then the patient receives nilotinib orally at the dose of 800 mg/day (400 mg twice a day) for 7 days. The patient is scheduled for surgery the morning after the last take of the nilotinib (12 hours). When the colectomy is performed, the surgeon collects different tumoral samples which are immediately delivered to the laboratory.
Receives: Drug: Nilotinib

What is being measured

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

  1. ZAK expression level by immunohistochemistry on frozen material (surgical specimen) by Western blot and on paraffinembedded tissues section using an immunohistochemistry approach

    Measured: Day 0

  2. ZAK expression level by immunohistochemistry on frozen material (surgical specimen) by Western blot and on paraffinembedded tissues section using an immunohistochemistry approach

    Measured: Day 7

Secondary outcomes (7)

  1. Efficacy of the 7day nilotinib treatment based on histological response as measured with tumour regression grade

    Measured: Day 7

  2. Efficacy of the 7day nilotinib treatment based on histological response as measured with the proportion of tumour necrosis

    Measured: Day 7

  3. Efficacy of the 7day nilotinib treatment based on histological response as measured with the type of tumour necrosis

    Measured: Day 7

  4. Incidence of Treatment Emergent Adverse Events as assessed by CTCAE v4.0 as assessed by CTCAE v4.0

    Measured: through study completion, an average of 2 years

  5. Postoperative complications as assessed by Dindo and Clavien classification

    Measured: through study completion, an average of 2 years

  6. Maximum Plasma Concentration [Cmax] of nilotinib .

    Measured: Day 7, day 8

  7. Half-life of nilotinib

    Measured: Day 7

Timeline

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

  1. First posted17 May 2016 (estimated)
  2. Study startMay 2016
  3. Primary completionNov 2017 (estimated)
  4. Study completionNov 2017 (estimated)

Why it stopped: none participant has been enrolled and recruited during the first year after competent autority autorisation.

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
Early Phase 1
Primary purpose
Other
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02774512
Sponsor's protocol ID
IB 2015-03
Acronym
ZAK-0
Status last verified
Sep 2017
First submitted
27 Apr 2016
Last updated
6 Oct 2017
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Nilotinib in people with Colon Cancer, run by Institut Bergonié at 1 site in France.

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 18 inclusion and 22 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: withdrawn, as of the sponsor's last update on 6 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 1 site in France. 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 phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

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 was withdrawn before enrolling participants, so there are no results.

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?

ZAK expression level by immunohistochemistry on frozen material (surgical specimen) by Western blot and on paraffinembedded tissues section using an immunohistochemistry approach (time frame: Day 0). The study lists 2 primary outcomes in all. 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 NCT02774512.

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 6 Oct 2017.

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