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

NCT02774512 | Withdrawn Early Phase 1

• 1 other identifier: IB 2015-03
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Colon Cancer

Outcome Measures

Primary Outcomes (2)

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

  Day 0

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

  Day 7

Secondary Outcomes (7)

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

  Day 7

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

  Day 7

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

  Day 7

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

  through study completion, an average of 2 years

• Postoperative complications as assessed by Dindo and Clavien classification

  through study completion, an average of 2 years

Study Arms (1)

Nilotinib

EXPERIMENTAL

A 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.

Drug: Nilotinib

Interventions

Nilotinib DRUG

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.

Nilotinib

Eligibility Criteria

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

You may qualify if:

• 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.
• 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:
• 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

You may not qualify if:

• 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:
• 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).
• 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.

Sponsors & Collaborators

• Institut Bergonié: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

Institut Bergonié

Bordeaux, 33076, France

Location

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

nilotinib

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2016
• First Posted: May 17, 2016
• Study Start: May 1, 2016
• Primary Completion: November 1, 2017
• Study Completion: November 1, 2017
• Last Updated: October 6, 2017

Record last verified: 2017-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)