cancer malignancies
Conditions
Interventions
This is a proof of concept and pharmacological phase 0 crossover study whereby
the new oral formulation of capecitabine, ModraCape001, will be investigated.
The primary endpoint is to determine the
Sponsors
Antoni van Leeuwenhoek Ziekenhuis
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: • 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 = 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.
Exclusion criteria
Exclusion criteria: • 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary study parameters correspond to the primary endpoints and include the following: pharmacokinetic parameters (Cmax, Tmax, t*, AUC0-t, AUCinf, MRT, Vd and Cl). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary study parameters correspond to the secondary endpoints and include the following: • AUC of capecitabine, 5-dFCR, 5-dFUR and 5-FU; • AUC of intracellular metabolites: FUMP, FUDP, FUTP, FdUMP, FdUDP and FdUTP; • Enzyme activity of dihydropyrimidine dehydrogenase (DPD) in PBMCs; • Preliminary safety (NCI CTCAE criteria version 4) | — |
Countries
Netherlands
Outcome results
None listed