Proof of principle and pharmacological phase 0 crossover study with controlled release capecitabine (ModraCape001)
- Conditions
- cancermalignancies10027655
- Registration Number
- NL-OMON37961
- Lead Sponsor
- Antoni van Leeuwenhoek Ziekenhuis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 39
• Histological or cytological proof of cancer;• Patients who might benefit from treatment with capecitabine, e.g. colon, breast, adenocarcinoma of unknown primary (ACUP), pancreatic and gastric carcinoma;;• Age >= 18 years;• WHO performance status of 0, 1 or 2;;• Able and willing to give written informed consent;• Able and willing to undergo blood sample collection for PK measurements;;• Life expectancy >= 3 months;;• Minimal acceptable safety laboratory values;a. ANC of >= 1.5 x 10^9 /L;;b. Platelet count of >= 100 x 10^9 /L;;c. Hemoglobin >= 6.5 mmol/L;;d. Hepatic function as defined by serum bilirubin <= 1.5 x ULN, ALAT and ASAT <= 2.5 x ULN;;e. Renal function as defined by serum creatinine <= 1.5 x ULN or creatinine clearance >= 50 ml/min (by Cockcroft-Gault formula).;• No radio- or chemotherapy within the last 21 days prior to study entry (palliative limited radiation of 1 x 8 Gy for pain reduction is allowed);;• Able and willing to swallow oral medication;;• Negative pregnancy test (urine/serum) for female patients with childbearing potential.
• Dihydropyrimidine dehydrogenase (DPD) deficiency as assessed on the basis of DPYD mutation analysis (DPYD*2A);;• Women who are pregnant or breast feeding;;• 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);;• Bowel obstructions or motility disorders that may influence the absorption of drugs;;• Pre-existing neuropathy > grade 1;;• Unresolved (> grade 1) toxicities of previous chemotherapy;;• Patients with known alcoholism, drug addiction and/or psychotic disorders in the history that are not suitable for adequate follow up;;• The use of any drug or complementary alternative medicine that might interfere with the biotransformation of capecitabine and/or 5FU, like: acenocoumarol, allopurinol, folic acid, folinic acid (leucovorin), interferon alpha, metronidazol, phenprocoumon, phenytoin, sorivudine (and analogues) and warfarin;;• Current participation or previous participation in a study with an investigational compound, or chemo- and/or radiotherapy within 21 days of receiving first dose of study medication. (Palliative limited radiation of 1 x 8 Gy for pain reduction is allowed);;• Prior stem cell or bone marrow transplant; ;• Known hypersensitivity to the components of the combination study therapy or its analogs;;• Uncontrolled infectious disease or known Human Immunodeficiency Virus HIV-1 or HIV-2 type patients;;• Patients with a known history of hepatitis B or C;;• Symptomatic cerebral or leptomeningeal metastases;;• Neurologic disease that may render a patient at increased risk for peripheral or central neurotoxicity;;• Evidence of any other disease, neurological or metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment-related complications.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary study parameters correspond to the primary endpoints and include the<br /><br>following: pharmacokinetic parameters (Cmax, Tmax, t*, AUC0-t, AUCinf, MRT, Vd<br /><br>and Cl).</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary study parameters correspond to the secondary endpoints and include<br /><br>the following:<br /><br>• AUC of capecitabine, 5-dFCR, 5-dFUR and 5-FU;<br /><br>• AUC of intracellular metabolites: FUMP, FUDP, FUTP, FdUMP, FdUDP and FdUTP;<br /><br>• Enzyme activity of dihydropyrimidine dehydrogenase (DPD) in PBMCs;<br /><br>• Preliminary safety (NCI CTCAE criteria version 4)</p><br>