Solid Tumor, AdultPhase 1NCT05242926
Absorption and Excretion of Oral Docetaxel
A Phase 1 study testing ModraDoc006/r in people with Solid Tumor, Adult, run by Modra Pharmaceuticals at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumor, Adult
- What is being tested?
- ModraDoc006/r
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteNetherlands
- Study dates
- Oct 2017to Jun 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
- No radio- or chemotherapy within 4 weeks prior to the first dose of ModraDoc006/r (palliative radiation on a limited field for pain control is allowed)
- Able and willing to swallow oral medication.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Netherlands Cancer Institute - Antoni van Leeuwenhoek
Amsterdam, 1066 CX
About this study
Official title: Absorption and Excretion of Docetaxel (as ModraDoc 006 Tablets) After Oral Administration in Combination With Ritonavir
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.
Read the detailed description
Oral administration of (anticancer) drugs has many advantages over the intravenous route. However, oral bioavailability of the docetaxel IV-formulation is low and variable. The bioavailability of docetaxel is limited due to metabolizing cytochrome P450 (CYP) enzymes, especially CYP3A, which are abundantly present in the gastrointestinal tract. Inhibition of CYP3A4 enzymes with ritonavir has proven to enhance the bioavailability of oral docetaxel in several pre-clinical and early clinical studies.
The Pharmacy of The Netherlands Cancer Institute has developed a new oral formulation of docetaxel (ModraDoc006), which contains a spray dried docetaxel powder resulting in an increased apparent solubility and therefore improved uptake from the gastrointestinal tract. The oral docetaxel ModraDoc006 tablet formulation, has been investigated in two phase I trials in combination with ritonavir. The combination of ModraDoc006/ritonavir resulted in a significantly increased bioavailability, reaching an exposure in terms of the area under plasma concentration-time curve (AUC) comparable to exposure observed after intravenous administration of weekly docetaxel at 35 mg/m2. Commonly observed toxicities in the phase I trials were nausea, diarrhea, fatigue, vomiting and alopecia, most being of grade 1-2.
The metabolism of docetaxel (as ModraDoc006) after oral administration in combination with ritonavir has not been investigated yet, nor have the routes of elimination been explored. Phase I clinical trials have focused on safety and pharmacokinetics of oral docetaxel after weekly once daily and bi-daily administration.
An absorption and excretion study after oral administration of a bi-daily dose of ModraDoc006/ritonavir can provide essential knowledge on the absorption, metabolism and excretion of this formulation of docetaxel. This knowledge can be used for further development. Using validated LC-MS/MS assays, docetaxel can be quantified in plasma, urine and faeces. Further analysis using a combination of chromatography, UV spectrometry and mass spectrometry may result in detection and quantification of its known metabolites M1, M2, M3 and M4 and as yet unidentified metabolites.
- Conditions
- Solid Tumor, Adult
- Being tested
- ModraDoc006/r
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ModraDoc006/rDrug
Also called oral docetaxel formulation
One time bi-daily dosing (30/20 mg) of ModraDoc006 in combination with ritonavir 100 mg tablets
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: ModraDoc006/r |
What is being measured
The primary outcome is the main question the study is designed to answer.
The absorption of oral docetaxel
Using validated LC-MS/MS assays, docetaxel can be quantified in plasma
Measured: Pharmacokinetic sampling during 48 hours - 168 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Feb 2022
- Study startOct 2017 (estimated)
- Primary completionApr 2018 (estimated)
- Study completionJun 2018 (estimated)
Why it stopped: Pending further development
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid Tumor, AdultStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Modra Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Serena Marchetti, MD/PhD, Principal investigator, The Netherlands Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05242926
- Sponsor's protocol ID
- N16AED
- Status last verified
- Feb 2022
- First submitted
- 17 Jul 2017
- Last updated
- 16 Feb 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Absorption and Excretion of Docetaxel (as ModraDoc 006 Tablets) After Oral Administration in Combination With Ritonavir
- ClinicalTrials.gov ID
- NCT05242926
- Acronym / sponsor ID
- N16AED
- Conditions
- Solid Tumor, Adult
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Pending further development
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Modra PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Oct 2017 (estimated)
- Primary completion
- Apr 2018 (estimated)
- Study completion
- Jun 2018 (estimated)
- First posted
- 16 Feb 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Oral administration of (anticancer) drugs has many advantages over the intravenous route. However, oral bioavailability of the docetaxel IV-formulation is low and variable. The bioavailability of docetaxel is limited due to metabolizing cytochrome P450 (CYP) enzymes, especially CYP3A, which are abundantly present in the gastrointestinal tract. Inhibition of CYP3A4 enzymes with ritonavir has proven to enhance the bioavailability of oral docetaxel in several pre-clinical and early clinical studies.
The Pharmacy of The Netherlands Cancer Institute has developed a new oral formulation of docetaxel (ModraDoc006), which contains a spray dried docetaxel powder resulting in an increased apparent solubility and therefore improved uptake from the gastrointestinal tract. The oral docetaxel ModraDoc006 tablet formulation, has been investigated in two phase I trials in combination with ritonavir. The combination of ModraDoc006/ritonavir resulted in a significantly increased bioavailability, reaching an exposure in terms of the area under plasma concentration-time curve (AUC) comparable to exposure observed after intravenous administration of weekly docetaxel at 35 mg/m2. Commonly observed toxicities in the phase I trials were nausea, diarrhea, fatigue, vomiting and alopecia, most being of grade 1-2.
The metabolism of docetaxel (as ModraDoc006) after oral administration in combination with ritonavir has not been investigated yet, nor have the routes of elimination been explored. Phase I clinical trials have focused on safety and pharmacokinetics of oral docetaxel after weekly once daily and bi-daily administration.
An absorption and excretion study after oral administration of a bi-daily dose of ModraDoc006/ritonavir can provide essential knowledge on the absorption, metabolism and excretion of this formulation of docetaxel. This knowledge can be used for further development. Using validated LC-MS/MS assays, docetaxel can be quantified in plasma, urine and faeces. Further analysis using a combination of chromatography, UV spectrometry and mass spectrometry may result in detection and quantification of its known metabolites M1, M2, M3 and M4 and as yet unidentified metabolites.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| ModraDoc006/r | Experimental | Drug: ModraDoc006/rSix 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ModraDoc006/rAlso: oral docetaxel formulationOne time bi-daily dosing (30/20 mg) of ModraDoc006 in combination with ritonavir 100 mg tablets | Drug | ModraDoc006/r |
Primary outcome
The absorption of oral docetaxel
Time frame: Pharmacokinetic sampling during 48 hours - 168 hours
Using validated LC-MS/MS assays, docetaxel can be quantified in plasma
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Feb 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Serena Marchetti, MD/PhD principal investigator
The Netherlands Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ModraDoc006/r in people with Solid Tumor, Adult, run by Modra Pharmaceuticals at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 16 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The absorption of oral docetaxel (time frame: Pharmacokinetic sampling during 48 hours - 168 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Feb 2022.