Weekly Administration of (bi-)Daily Oral Docetaxel in Combination With Ritonavir

• Status: Completed
• Trial end date: 2017-01-26
• Target enrollment: 0
• Participant gender: All

Summary

Oral administration has many advantages above intravenously administrated drugs for patients. Up to now, oral administration of docetaxel as single agent has not been feasible due to low and variable bioavailability. This low systematic exposure to docetaxel can effectively be increased after co-administration of ritonavir. The department of pharmacy of the Slotervaart Hospital and Netherlands Cancer Institute developed a solid oral dosage form for docetaxel, ModraDoc001 10 mg capsules.

Two other novel dosage forms of docetaxel with improved pharmaceutical characteristics, have been developed: ModraDoc003 10 mg tablets and ModraDoc004 10/50 mg tablets. The systemic exposure after administration of those forms is now being investigated.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: The Netherlands Cancer Institute
• Treatments: Docetaxel; Ritonavir

Criteria

Inclusion Criteria:

1. Histological or cytological proof of cancer

2. Patients 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 cancers, prostate cancer and carcinoma of unknown primary site.

4. Age _ 18 years

5. Able and willing to give written informed consent

6. Able and willing to undergo blood sampling for pharmacokinetics

7. Life expectancy _ 3 months allowing adequate follow up of toxicity evaluation and anti-tumor activity

8. Minimal acceptable safety laboratory values

• ANC of _ 1.5 x 109 /L

• Platelet count of _ 100 x 109 /L

• Hepatic function as defined by serum bilirubin _ 1.5 x ULN, ALAT and ASAT _ 2.5 x ULN

• 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 _ 2

10. No radio- or chemotherapy within the last 4 weeks prior to study entry (palliative limited radiation for pain reduction is allowed)

11. 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. 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, quinidine, quinine, tamoxifen, megestrol and grapefruit juice, concomitant use of HIV medications; other protease inhibitors,(non) nucleoside analoga, 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

7. Bowel obstructions or motility disorders that may influence the absorption of drugs

8. Chronic use of H2-receptor antagonists or proton pump inhibitors

9. Neurologic disease that may render a patient at increased risk for peripheral or central neurotoxicity

10. Pre-existing neuropathy greater than CTC grade 1

11. Symptomatic cerebral or leptomeningeal metastases

12. 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.