Patients with cancer who might benefit from treatment with capecitabine, e.g. colon, breast, pancreatic and gastric cancer, ACUP.
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 ph
50% of the mean AUC of capecitabine after intake of the same dose of Xeloda® and if the mean AUC of capecitabine up to 2 hours (AUC0-2) with ModraCape is <50 % of that observed with Xeloda®. The latte
Sponsors
The Netherlands Cancer Institute
Eligibility
Inclusion criteria
Inclusion criteria: 1. Histological or cytological proof of cancer; 2. Patient who might benefit from treatment with capecitabine, e.g. colon, breast, pancreatic and gastric cancer, ACUP; 3. Age: 18 years or older; 4. WHO performance status of 0, 1 or 2; 5. Able and willing to give written informed consent; 6. Able and willing to undergo blood sample collection for pharmacokinetic (PK) measurements and biomarker analysis; 7. ife expectancy is at least 3 months allowing adequate follow up; 8. Minimal acceptable safety laboratory values: A. ANC of at least 1.5 x 109 /L; B. Platelet count of at least 100 x 109 /L; C. Hemoglobin of at least 6.5 mmol/L; D. Hepatic function as defined by serum bilirubin not higher than 1.5 x ULN, ALAT and ASAT not higher than 3.0 x ULN (not higher than 5 x ULN in case of liver metastases); E. Renal function as defined by serum creatinine not higher than 1.5 x ULN or creatinine clearance at least 50 ml/min (by Cockcroft-Gault formula). 9. No radio- or chemotherapy within 3 weeks of receiving first dose of study medication (palliative limited radiation of 1 x 8 Gy for pain reduction is allowed); 10. Able and willing to swallow oral medication; 11. Negative pregnancy test (urine/serum) for female patients with childbearing potential.
Exclusion criteria
Exclusion criteria: 1. Dihydropyrimidine dehydrogenase (DPD) deficiency as assessed on the basis of DPYD mutation analysis; 2. Women who are pregnant or breast feeding; 3. 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); 4. Bowel obstructions or motility disorders that may influence the absorption of drugs; 5. Pre-existing neuropathy > grade 1; 6. Unresolved (> grade 1) toxicities (except alopecia) of previous chemotherapy; 7. Patients with known alcoholism, drug addiction and/or psychotic disorders in the history that are not suitable for adequate follow up; 8. The use of any drug or complementary alternative medicine that might interfere with the biotransformation of capecitabine and/or 5FU, like CYP2C9 substrates with narrow therapeutic windows (e.g., vitamin K antagonizing anticoagulants [acenocoumarol, phenprocoumon, warfarin], phenytoin), allopurinol, folic acid, folinic acid, interferon alpha, metronidazol, sorivudine (and analogues), aluminium hydroxide and magnesium hydroxide; 9. 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); 10. Prior stem cell or bone marrow transplant; 11. Known hypersensitivity to the components of the study drug or its analogs; 12. Uncontrolled infectious disease or known Human Immunodeficiency Virus HIV-1 or HIV-2 type patients; 13. Patients with a known history of hepatitis B or C; 14. Symptomatic cerebral or leptomeningeal metastases; 15. Neurologic disease that may render a patient at increased risk for peripheral or central neurotoxicity; 16. 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 |
|---|---|
| To determine the plasma pharmacokinetics of capecitabine after intake of different formulations of ModraCape and after intake of Xeloda®. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. To determine the plasma AUC of capecitabine and its metabolites 5-dFCR, 5-dFUR and 5-FU after administration of different ModraCape formulations and Xeloda; 2. To determine the intracellular pharmacokinetics of 5-FU nucleotides after administration of different formulations of ModraCape or Xeloda; 3. To determine dihydropyrimidine dehydrogenase (DPD) enzyme activity in peripheral blood mononuclear cells (PBMCs); 4. To determine thymidylate synthase (TS) enzyme activity in peripheral blood mononuclear cells (PBMCs); 5. To determine the preliminary safety and tolerability profile of different formulations of ModraCape. | — |
Contacts
Public ContactBart Jacobs
The Netherlands Cancer Institute NKI-AvL Plesmanlaan 121
Outcome results
None listed