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Absorption and excretion of docetaxel (as ModraDoc 005 tablets) after oral administration in combination with ritonavir.

Withdrawn
Conditions
10027655
cancer
malignancy
Registration Number
NL-OMON38495
Lead Sponsor
Antoni van Leeuwenhoek Ziekenhuis
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Withdrawn
Sex
Not specified
Target Recruitment
6
Inclusion Criteria

1. Histological or cytological proof of cancer;
2. Patient for whom no standard therapy of proven benefit exist;
3. Patients who might benefit from treatment with docetaxel, e.g. advanced breast, gastric, esophagus, bladder, ovarian cancer and non-small cell lung cancer, head and neck cancer, prostate cancer and carcinoma of unknown primary site.
4. Age * 18 years;
5. Able and willing to give written informed consent;
6. WHO performance status of 0, 1 or 2;
7. Able and willing to undergo blood sampling , urine and faeces sampling for PK;
8. Able and willing to comply with the study protocol for the duration of the study;
9. Life expectancy * 3 months allowing adequate follow up of toxicity evaluation and antitumor activity;
10. Evaluable disease according to RECIST 1.1 criteria;
11. 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 (or * 5 x ULN in case of liver metastases)
d. Renal function as defined by serum creatinine * 1.5 x ULN or creatinine clearance * 50 ml/min (by Cockcroft-Gault formula).
12. Negative pregnancy test (urine/serum) for female patients with childbearing potential;
13. No radio- or chemotherapy within the last 4 weeks prior to study entry (palliative limited radiation for pain control is allowed)
14. Able and willing to swallow oral medication

Exclusion Criteria

1. Patients with known alcoholism, drug addiction and/or psychotic disorders in the history that are not suitable for adequate follow up
2. Women who are pregnant or breast feeding.
3. 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).
4. Concomitant use of MDR and CYP3A modulating drugs, including but not limited to Ca¬¬+-entry blockers (verapamil, dihydropyridines), cyclosporine, quinidine, quinine, tamoxifen, megestrol and grapefruit juice, concomitant use of HIV medications; other protease inhibitors, (non) nucleoside analogs, St. Johns wort or macrolide antibiotics as erythromycin and clarithromycin.
5. Uncontrolled infectious disease or known HIV-1 or HIV-2 type patients
6. Unresolved (>grade 1) toxicities of previous chemotherapy, excluding alopecia
7. Bowel obstructions or motility disorders that may influence the absorption of drugs
8. Neurologic disease that may render a patient at increased risk for peripheral or central neurotoxicity
9. Pre-existing neuropathy greater than CTC grade 1
10. Symptomatic cerebral or leptomeningeal metastases
11. 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.
12. Legal incapacity

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
<p>To quantitatively determine the absorption and excretion of docetaxel (as<br /><br>ModraDoc005 10 mg tablets) after administration of a single low dose and a<br /><br>single high dose of oral docetaxel in combination with ritonavir.</p><br>
Secondary Outcome Measures
NameTimeMethod
<p>* To investigate the presence or absence of quantitatively relevant metabolites<br /><br>of docetaxel as ModraDoc005 10 mg tablets in plasma, faeces and urine.<br /><br>* To preliminary assess anti-tumor activity of oral docetaxel as ModraDoc005 10<br /><br>mg tablets combined with ritonavir<br /><br>* To further characterize the safety and tolerability of oral docetaxel as<br /><br>ModraDoc005 10 mg tablets in combination with ritonavir.</p><br>
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