Cancer, oral, paclitaxel, low dose metronomic, phase 1, kanker, oraal, laaggedoseerd, metronoom, fase 1
Conditions
Interventions
Patients with histological or cytological proof of cancer (excluding patients with secondary breast cancer metastasis with only lung metastases and primary brain tumors) for whom no standard treatment
Sponsors
The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
Eligibility
Inclusion criteria
Inclusion criteria: 1. Patients with histological or cytological proof of cancer who might benefit from treatment with paclitaxel (excluding patients with secondary breast cancer metastasis with only lung metastases and primary brain tumors); 2. Patients for whom no standard therapy of proven benefit exist; 3. Patients have evaluable disease; 4. Age ≥ 18 years; 5. Able and willing to give written informed consent; 6. Able and willing to undergo blood sampling for pharmacokinetics and pharmacodynamics; 7. Life expectancy ≥ 3 months allowing adequate follow up of toxicity evaluation and antitumor activity; 8. Minimal acceptable safety laboratory values: A. ANC of ≥ 1.5 x 109 /L; B. Platelet count of ≥ 100 x 109 /L; C. Hepatic function as defined by serum bilirubin ≤ 1.5 x ULN, ALAT and ASAT ≤ 2.5 x ULN; D. Renal function as defined by serum creatinine ≤ 1.5 x ULN or creatinine clearance ≤ 50 ml/min (by Cockcroft-Gault formula). 9. WHO performance status of 0, 1 or 2; 10. No radio- or chemotherapy within the last 4 weeks prior to study entry, unless this concerns single dose radiotherapy for pain palliation; 11. Able and willing to swallow oral medication.
Exclusion criteria
Exclusion criteria: 1. Patients with known alcoholism, drug addiction, psychotic disorders in the history and/or other reasons, for which they are not amenable for adequate follow up; 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. Concomitant use of MDR and CYP3A modulating drugs such as Ca¬¬+-entry blockers (verapamil, dihydropyridines), cyclosporine, (non) nucleoside analoga, St. Johns worth, macrolide antibiotics as erythromycin and clarithromycin, quinidine, quinine, tamoxifen, megestrol, grapefruit juice, concomitant use of HIV medications or other protease inhibitors; 5. Uncontrolled infectious disease or known HIV-1 or HIV-2 type patients; 6. Unresolved (>grade 1) toxicities of previous chemotherapy, excluding alopecia; 7. Known allergic reaction against contrast agents; 8. Bowel obstructions or motility disorders that may influence the absorption of drugs; 9. Chronic use of H2-receptor antagonists or proton pump inhibitors; 10. Neurologic disease that may render a patient at increased risk for peripheral or central neurotoxicity; 11. Pre-existing neuropathy greater than CTC grade 1; 12. Symptomatic cerebral or leptomeningeal metastases; 13. 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 safety and feasibility of LDM bi-daily oral paclitaxel (as ModraPac001 capsules) in combination with boosting agent ritonavir. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. To determine the recommended dose (RD) of bi-daily oral paclitaxel in combination with ritonavir; 2. To determine the maximal tolerated dose (MTD, or maximal safe dose) to assess the safety range; 3. Pharmacokinetics of paclitaxel and ritonavir in this schedule; 4. Usefulness and feasibility of exploratory biomarkers: A. Levels of CEC and CEP; B. Serum levels and gene expression of thrombospondin-1 (TSP-1); C. To preliminary asses the efficacy of LDM treatment, measured by PFS, response rates, duration of response and duration of disease control. 5. To establish the effect of functional genetic polymorphisms in six genes (SLCO1B3, ABCB1, ABCC2, CYP3A4, CYP3A5 and CYP2C8 on the pharmacokinetics and pharmacodynamics of oral paclitaxel and ritonavir. | — |
Contacts
Public ContactS. Marchetti
The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital Clinical Pharmacology Department of Medical Oncology Plesmanlaan 121
Outcome results
None listed