colon carcinoma MedDRA version: 20.0 Level: PT Classification code 10052358 Term: Colorectal cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: vinorelbine
Pharmaceutical Form: Infusion
INN or Proposed INN: VINORELBINE
CAS Number: 71486-22-1
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentratio
Sponsors
Netherlands Cancer Institute- Antoni van Leeuwenhoek hospital (NKI-AVL)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent (+ TR (translational research)) must be given according to ICH/GCP and national/local regulations 2. Written documentation of BRAF-like signature CC, including BRAFm and BRAFwt, as determined by the validated assay of Agendia 3. Age = 18 years 4. Histologically proven and measurable (RECIST criteria v.1.1) metastatic adenocarcinoma of the colon not in a previously irradiated area, treated with one or two lines of standard of care therapy, including BRAF inhibitors, for locally advanced disease and metastatic disease 5. WHO performance status of 0-1 6. Life expectancy > 3 months allowing adequate follow up of toxicity evaluation and antitumor activity 7. Negative urine pregnancy test for female patients with childbearing potential Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 32 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. Any treatment with investigational drugs, including BRAF inhibitors, within 28 days prior to receiving the first dose of investigational treatment 2. Symptomatic or untreated leptomeningeal disease 3. Symptomatic brain metastasis. Patients previously treated or untreated for these conditions that are asymptomatic in the absence of corticosteroid and anticonvulsant therapy (for at least 4 weeks) are allowed to enroll. Radiotherapy for brain metastasis must have been completed at least 6 weeks prior to start of study treatment. Brain metastasis must be stable with verification by imaging (e.g. brain MRI or CT completed at screening demonstrating no current evidence of progressive brain metastases). Patients are not permitted to receive enzyme inducing anti-epileptic drugs or corticosteroids 4. Impairment of gastrointestinal (GI) function or GI disease (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, any condition inducing malabsorption, small bowel resection) 5. Other uncontrolled concomitant illness, including serious uncontrolled intercurrent infection 6. Known allergy or any other adverse reaction to any of the drugs or to any related compound 7. Women who are pregnant or breast feeding 8. Unreliable contraceptive methods. Both men and women enrolled in this trial must agree to use a reliable contraceptive method throughout the study (adequate contraceptive methods are: condom, sterilization, other barrier contraceptive measures preferably in combination with condoms) 9. Patients who have undergone any major surgery within the last 2 weeks prior to starting study drug or who would not have fully recovered from previous surgery 10. Uncontrolled infectious disease or known Human Immunodeficiency Virus HIV-1 or HIV-2 type patients 11. Patients with a known history of hepatitis B or C 12. Known hypersensitivity to study drug or excipients
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the anti-tumor activity, as defined as doubling of progression free survival (PFS) of vinorelbine treatment in patients with BRAF-like colon cancer. This means that by vinorelbine treatment the rate of progression at 6 weeks drops to 25%.;Secondary Objective: • To characterize the safety and tolerability of vinorelbine, as assessed by the incidence and severity of adverse events. • To assess efficacy of vinorelbine, as measured by overall response rate, duration of response, time to response and overall survival (OS). • To explore determinants (gene alteration/expression) of response to vinorelbine, as measured by baseline molecular status (mutation/ expression) in tumor tissue of potential predictive markers of tumor response. • To explore the potential mechanism of resistance to vinorelbine, as measured by gene alterations/expression profiles (i.e. baseline, relapse) in tumor tissue upon progression.;Primary end point(s): To demonstrate the safety and anti-tumor activity of vinorelbine in paitents with BRAF-like colon cancer, who are previously treated with maximally two lines of standard of care therapy for advanced disease. The study will be powered to demonstrate a doubling of progression free survival (PFS) of vinorelbine treatment compared with historic controls. This means that by vinorelbine treatment the rate of progression at 6 weeks drops to 25%;Timepoint(s) of evaluation of this end point: At the end of the trial | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • To characterize the safety and tolerability of vinorelbine, as assessed by the incidence and severity of adverse events. • To assess efficacy of vinorelbine, as measured by overall response rate, duration of response, time to response and overall survival (OS). • To explore determinants (gene alteration/expression) of response to vinorelbine, as measured by baseline molecular status (mutation/ expression) in tumor tissue of potential predictive markers of tumor response. • To explore the potential mechanism of resistance to vinorelbine, as measured by gene alterations/expression profiles (i.e. baseline, relapse) in tumor tissue upon progression.;Timepoint(s) of evaluation of this end point: at the end of the trial | — |
Countries
Belgium, Spain
Contacts
Public ContactJan Schelens
Netherlands Cancer Institute
Outcome results
None listed