Absorption and Excretion of Oral Docetaxel

NCT05242926 | Withdrawn Phase 1 DMC

• 1 other identifier: N16AED
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, phase I study to investigate the influence of the bi-daily weekly dosing of ModraDoc006/ritonavir on the absorption and excretion of docetaxel in patients with advanced solid tumours. The pharmacokinetics, absorption and excretion of docetaxel will be investigated during the study. Patients will receive 30 mg in the morning / 20 mg in the afternoon ModraDoc006 with BID 100 mg ritonavir in a fasted condition (i.e. at least 1 hour before or 2 hours after any food assumption), followed by collection of plasma, faeces and urine samples.

Conditions

Solid Tumor, Adult

Outcome Measures

Primary Outcomes (1)

• The absorption of oral docetaxel

  Using validated LC-MS/MS assays, docetaxel can be quantified in plasma

  Pharmacokinetic sampling during 48 hours - 168 hours

Study Arms (1)

ModraDoc006/r

EXPERIMENTAL

Six evaluable patients will be included for collection of plasma, faeces and urine samples during 168 hours after one day of bi-daily dosing (30/20 mg) of ModraDoc006 in combination with ritonavir.

Drug: ModraDoc006/r

Interventions

ModraDoc006/r DRUG

One time bi-daily dosing (30/20 mg) of ModraDoc006 in combination with ritonavir 100 mg tablets

Also known as: oral docetaxel formulation

ModraDoc006/r

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological or cytological proof of cancer.
• 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.
• Age ≥ 18 years.
• Able and willing to give written informed consent.
• WHO performance status of 0, 1 or 2.
• Able and willing to undergo blood sampling, urine and faeces sampling for PK.
• Able and willing to comply with the study protocol for the duration of the study.
• Life expectancy ≥ 3 months.
• Evaluable disease
• 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 bilirubine ≤ 1.5 x ULN, ASAT and ALAT ≤ 2.5 x ULN (or ≤ 5 ULN in case of liver metastases)
• Renal function as defined by serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 ml/min (by Cockcroft-Gault formula)
• Negative pregnancy test (urine/serum) for female patients with childbearing potential.

You may not qualify if:

• Patients with known alcoholism, drug addiction and/or psychotic disorders in the history that are not suitable for adequate follow up.
• Women who are pregnant or breast-feeding.
• 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 described in section 8.8.3 and include condom, sterilization and other barrier contraceptive measures preferably in combination with condoms).
• Concomitant use of MDR and CYP3A modulating drugs, including but not limited to Ca2+-entry blockers (verapamil, dihydropyridines), cyclosporine, quinidine, quinine, tamoxifen, megestrol and grapefruit juice, concomitant use of HIV medications; other protease inhibitors, (non) nucleoside analogs, St. John's wort or macrolide antibiotics as erythromycin and clarithromycin. A washout period is established for all relevant drugs (see appendix VII).
• Uncontrolled infectious disease or known HIV-1 or HIV-2 type infection.
• Unresolved (\>grade 1) toxicities of previous chemotherapy, excluding alopecia.
• Bowel obstructions, motility disorders or previously performed extended abdominal surgery that may influence the absorption of drugs.
• Neurologic disease that may render a patient at increased risk for peripheral or central neurotoxicity.
• Pre-existing neuropathy greater than CTC grade 1.
• Patients with symptomatic brain metastases or with leptomeningeal metastases. Patients with brain metastases are allowed if they received adequate treatment, are asymptomatic in the absence of corticosteroid therapy and anticonvulsant therapy for at least 6 weeks. Radiotherapy for brain metastasis must have been completed at least 6 weeks prior to start of study treatment. Brain metastasis must be stable with verification by imaging (e.g. brain MRI or CT completed at screening).
• 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.

Sponsors & Collaborators

• Modra Pharmaceuticals: lead

Study Sites (1)

Netherlands Cancer Institute - Antoni van Leeuwenhoek

Amsterdam, 1066 CX, Netherlands

Location

Study Officials

• Serena Marchetti, MD/PhD

  The Netherlands Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Six evaluable patients will receive bidaily dosing on day 1 of week 1, whereafter collection of plasma, faeces and urine samples will take place until 168 hours after the first dosing.

Study Record Dates

• First Submitted: July 17, 2017
• First Posted: February 16, 2022
• Study Start: October 1, 2017
• Primary Completion: April 1, 2018
• Study Completion: June 1, 2018
• Last Updated: February 16, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)