Solid Tumor, AdultPhase 1NCT03147378
Food Effect Study of ModraDoc006 in Combination With Ritonavir
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 study aims to evaluate the effect of food on the pharmacokinetics of ModraDoc006 in combination with ritonavir, in an open-label, cross-over design. Patients will be randomized into two treatment groups receiving ModraDoc006/r week 1 under fasting and week 2 under fed condition, or vice versa. 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
- 18 participants
- Where
- 1 siteNetherlands
- Study dates
- 10 May 2017to 4 Apr 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 for whom no standard therapy of proven benefit exists
- 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.
- Age 18 years
- Able and willing to give written informed consent
- Able and willing to undergo blood sampling for pharmacokinetics
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- Life expectancy 3 months
- Minimal acceptable safety laboratory values 8.1. Hb ≥ 6.0 mmol/l 8.2. ANC 1.5 x 109 /L 8.3. Platelet count 100 x 109 /L 8.4. Serum bilirubin 1.5 x ULN, ALAT and ASAT 2.5 x ULN (or 5 x ULN in case of presence of liver metastases) 8.5. Serum creatinine 1.5 x ULN or creatinine clearance 50 ml/min (by Cockcroft-Gault formula).
- WHO performance status of 1
- No radio- or chemotherapy within the last 4 weeks prior to first dose of study medication (palliative radiation on limited field for pain reduction is allowed)
- Able and willing to swallow oral medication.
Who cannot join
- Patients with known alcoholism, drug addiction and/or psychotic disorders in the medical history that are not suitable for adequate follow up
- Women who are pregnant or breast-feeding.
- Men and women, who do not agree to use two reliable contraceptive methods hroughout the study (adequate contraceptive methods are: use of oral, injected or implanted hormonal methods of contraception, placement of an intrauterine device (IUD) or intrauterine system (IUS), barrier methods of contraception: condom, diaphragm with spermicide, male sterilization, true abstinence).
- 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 analogs, St. Johns wort or macrolide antibiotics like erythromycin and clarithromycin.
- Uncontrolled infectious disease or known HIV-1 or HIV-2 infection
- Unresolved (>grade 1) toxicities of previous chemotherapy, excluding alopecia
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- Bowel obstructions or motility disorders or previous 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 suspected or known brain metastases, unless they have been adequately treated and are asymptomatic without use of corticosteroids (for at least 1 month)
- 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.
- Legal incapacity
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: Food-effect Study of Weekly Administration of (bi-)Daily Oral Docetaxel (ModraDoc006) in Combination With Ritonavir
This study aims to evaluate the effect of food on the pharmacokinetics of ModraDoc006 in combination with ritonavir, in an open-label, cross-over design. Patients will be randomized into two treatment groups receiving ModraDoc006/r week 1 under fasting and week 2 under fed condition, or vice versa.
Read the detailed description
In this study the effect of food on the plasma exposure of ModraDoc006/ritonavir will be assessed in an open-label, cross-over design. Patients will receive ModraDoc006/ritonavir at the dose of 30 mg ModraDoc006 with 100 mg ritonavir.
Patients will be randomized 1:1 into two treatment groups (in total 16 evaluable patients are needed):
- Group A: will receive ModraDoc006/ritonavir under fasting conditions the first week and in a fed condition the second week of treatment.
- Group B: will receive ModraDoc006/ritonavir under fed condition the first week and under fasted condition the second week of treatment.
The department of pharmacy of The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital has developed a solid oral dosage form of docetaxel, ModraDoc006 10 mg tablets. This formulation has been investigated in two phase I clinical studies in combination with the CYP3A4 inhibitor ritonavir, according to a weekly once-daily (QD) or bi-daily (BID) schedule, respectively. Maximum Tolerated Dose (MTD) and pharmacokinetics of both regimes have been determined and further clinical testing is being planned, in particular of the weekly bi-daily regime.
The aim of the current study is to evaluate the effect of food on the pharmacokinetics of ModraDoc006 in combination with ritonavir. For the ritonavir tablet formulation used in this trial a food-effect on the bio-availability has been found in two prior studies. In these trials the plasma concentrations were lower when ritonavir was given after a moderate or high-fat meal. Plasma concentrations and T-lag were dependent on the type/amount of food administered. Concentrations were lower and T-lag longer when a high-fat meal was administered as compared to a moderate fat meal.
Randomization will be performed centrally at the Biometrics Department of the Netherlands Cancer Institute using a minimization technique as implemented in TENALEA©.
Pharmacokinetics will be performed in week 1 and 2 for up to 48 hours after study drug administration (see Pharmacokinetics paragraph for exact time points). Patients will receive a high-fat meal on the morning of the day of fed condition pharmacokinetics, half an hour prior to intake of ModraDoc006/ritonavir.
After week 2, the N15FED study will be completed and patients can be enrolled in the roll over study N17DEX to continue their treatment with ModraDoc006/r (at the dose of BID 30/20 mg ModraDoc006 in combination with BID 100 mg ritonavir) in their best interest and to assess the long-term safety of this treatment.
- 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
Treatment with weekly ModraDoc006 (oral docetaxel) 10mg tablets in combination with ritonavir 100mg tablets in fed or fasting condition
| Study group | Role | What they receive |
|---|---|---|
| arm A Fasting-Fed condition | Experimental | ModraDoc006/r will be administered in fasting condition week 1 and in fed condition week 2 Receives: Drug: ModraDoc006/r |
| arm B Fed-Fasting condition | Experimental | ModraDoc006/r will be administered in fed condition week 1 and in fasting condition week 2 Receives: Drug: ModraDoc006/r |
What is being measured
The primary outcome is the main question the study is designed to answer.
The AUC of docetaxel (area under the curve)
The AUC of docetaxel given as bi-daily ModraDoc006 10 mg tablets in combination with ritonavir after administration in a high fed and fasting condition
Measured: Pharmacokinetic sampling during 2 weeks, 0-48 hours after administration (i.e. the 2 treatment cycles)
The cMax (peak concentration) of docetaxel
The cMax (peak concentration) of docetaxel given as bi-daily ModraDoc006 10 mg tablets in combination with ritonavir after administration in a high fed and fasting condition
Measured: Pharmacokinetic sampling during 2 weeks, 0-48 hours after administration (i.e. the 2 treatment cycles)
Secondary outcomes (2)
The hematological and non-hematological toxicity profile of oral docetaxel in combination with ritonavir
The number of CTCAE v.4.03 grade 3-4 toxicities during treatment with ModraDoc006/r
Measured: Safety and tolerance will be evaluated during the complete study treatment untill 28 days after the last intake, using the CTCAEv4.03 grading system
The effect of functional genetic polymorphisms on the pharmacokinetics of oral docetaxel and ritonavir (to understand the mechanism of the drug-drug interaction more thoroughly)
Pharmacogenetic analyses will be performed for polymorphisms in drug metabolizing enzymes (e.g., but not limited to genes encoding for P-glycoprotein (ABCB1/MDR1), Multidrug resistance protein 2 (ABCC2/MRP2), Organic anion-transporting polypeptides 1B3 (OATP1B3), Cytochrome P450 (CYP) 3A4 and CYP3A5)
Measured: Sampling at baseline, the analyses will be performed retrospectively
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2017
- Study start10 May 2017
- Primary completion4 Apr 2018
- Study completion4 Apr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- Randomised
- Intervention model
- Crossover
- Model description
- After randomization eight patients will receive ModraDoc006/r in fasting condition week 1 and in fed condition week 2, and another eight patients will receive ModraDoc006/r in fed condition week 1 and in fasting condition week 2
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Modra Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- The Netherlands Cancer Institute
- Responsible party
- Sponsor
- Investigators
- Serena Marchetti, MD, PhD, Principal investigator, The Netherlands Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03147378
- Sponsor's protocol ID
- N15FED
- Status last verified
- Oct 2021
- First submitted
- 2 May 2017
- Last updated
- 19 Oct 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Vermunt MAC, de Weger VA, Janssen JM, Lopez-Yurda MI, Keessen M, Thijssen B, Rosing H, Huitema ADR, Beijnen JH, Marchetti S. Effect of Food on the Pharmacokinetics of the Oral Docetaxel Tablet Formulation ModraDoc006 Combined with Ritonavir (ModraDoc006/r) in Patients with Advanced Solid Tumours. Drugs R D. 2021 Mar;21(1):103-111. doi: 10.1007/s40268-020-00336-x. Epub 2021 Jan 19.
PubMed 33464545
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Food-effect Study of Weekly Administration of (bi-)Daily Oral Docetaxel (ModraDoc006) in Combination With Ritonavir
- ClinicalTrials.gov ID
- NCT03147378
- Acronym / sponsor ID
- N15FED
- Conditions
- Solid Tumor, Adult
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Modra PharmaceuticalsIndustry (pharma, biotech, devices)
- Collaborators
- The Netherlands Cancer Institute
- Study start
- 10 May 2017 (actual)
- Primary completion
- 4 Apr 2018 (actual)
- Study completion
- 4 Apr 2018 (actual)
- First posted
- 10 May 2017 (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 study aims to evaluate the effect of food on the pharmacokinetics of ModraDoc006 in combination with ritonavir, in an open-label, cross-over design. Patients will be randomized into two treatment groups receiving ModraDoc006/r week 1 under fasting and week 2 under fed condition, or vice versa.
Detailed description
In this study the effect of food on the plasma exposure of ModraDoc006/ritonavir will be assessed in an open-label, cross-over design. Patients will receive ModraDoc006/ritonavir at the dose of 30 mg ModraDoc006 with 100 mg ritonavir.
Patients will be randomized 1:1 into two treatment groups (in total 16 evaluable patients are needed):
- Group A: will receive ModraDoc006/ritonavir under fasting conditions the first week and in a fed condition the second week of treatment.
- Group B: will receive ModraDoc006/ritonavir under fed condition the first week and under fasted condition the second week of treatment.
The department of pharmacy of The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital has developed a solid oral dosage form of docetaxel, ModraDoc006 10 mg tablets. This formulation has been investigated in two phase I clinical studies in combination with the CYP3A4 inhibitor ritonavir, according to a weekly once-daily (QD) or bi-daily (BID) schedule, respectively. Maximum Tolerated Dose (MTD) and pharmacokinetics of both regimes have been determined and further clinical testing is being planned, in particular of the weekly bi-daily regime.
The aim of the current study is to evaluate the effect of food on the pharmacokinetics of ModraDoc006 in combination with ritonavir. For the ritonavir tablet formulation used in this trial a food-effect on the bio-availability has been found in two prior studies. In these trials the plasma concentrations were lower when ritonavir was given after a moderate or high-fat meal. Plasma concentrations and T-lag were dependent on the type/amount of food administered. Concentrations were lower and T-lag longer when a high-fat meal was administered as compared to a moderate fat meal.
Randomization will be performed centrally at the Biometrics Department of the Netherlands Cancer Institute using a minimization technique as implemented in TENALEA©.
Pharmacokinetics will be performed in week 1 and 2 for up to 48 hours after study drug administration (see Pharmacokinetics paragraph for exact time points). Patients will receive a high-fat meal on the morning of the day of fed condition pharmacokinetics, half an hour prior to intake of ModraDoc006/ritonavir.
After week 2, the N15FED study will be completed and patients can be enrolled in the roll over study N17DEX to continue their treatment with ModraDoc006/r (at the dose of BID 30/20 mg ModraDoc006 in combination with BID 100 mg ritonavir) in their best interest and to assess the long-term safety of this treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- After randomization eight patients will receive ModraDoc006/r in fasting condition week 1 and in fed condition week 2, and another eight patients will receive ModraDoc006/r in fed condition week 1 and in fasting condition week 2
| Arm | Type | Receives |
|---|---|---|
| arm A Fasting-Fed condition | Experimental | Drug: ModraDoc006/rModraDoc006/r will be administered in fasting condition week 1 and in fed condition week 2 |
| arm B Fed-Fasting condition | Experimental | Drug: ModraDoc006/rModraDoc006/r will be administered in fed condition week 1 and in fasting condition week 2 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Histological or cytological proof of cancer
- Patients for whom no standard therapy of proven benefit exists
- 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.
- Age 18 years
- Able and willing to give written informed consent
Key exclusion criteria (12 listed)
- Patients with known alcoholism, drug addiction and/or psychotic disorders in the medical history that are not suitable for adequate follow up
- Women who are pregnant or breast-feeding.
- Men and women, who do not agree to use two reliable contraceptive methods hroughout the study (adequate contraceptive methods are: use of oral, injected or implanted hormonal methods of contraception, placement of an intrauterine device (IUD) or intrauterine system (IUS), barrier methods of contraception: condom, diaphragm with spermicide, male sterilization, true abstinence).
- 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 analogs, St. Johns wort or macrolide antibiotics like erythromycin and clarithromycin.
- Uncontrolled infectious disease or known HIV-1 or HIV-2 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 formulationTreatment with weekly ModraDoc006 (oral docetaxel) 10mg tablets in combination with ritonavir 100mg tablets in fed or fasting condition | Drug | arm A Fasting-Fed condition, arm B Fed-Fasting condition |
Primary outcome
The AUC of docetaxel (area under the curve)
Time frame: Pharmacokinetic sampling during 2 weeks, 0-48 hours after administration (i.e. the 2 treatment cycles)
The AUC of docetaxel given as bi-daily ModraDoc006 10 mg tablets in combination with ritonavir after administration in a high fed and fasting condition
The cMax (peak concentration) of docetaxel
Time frame: Pharmacokinetic sampling during 2 weeks, 0-48 hours after administration (i.e. the 2 treatment cycles)
The cMax (peak concentration) of docetaxel given as bi-daily ModraDoc006 10 mg tablets in combination with ritonavir after administration in a high fed and fasting condition
2 secondary outcomes
The hematological and non-hematological toxicity profile of oral docetaxel in combination with ritonavir
Time frame: Safety and tolerance will be evaluated during the complete study treatment untill 28 days after the last intake, using the CTCAEv4.03 grading system
The effect of functional genetic polymorphisms on the pharmacokinetics of oral docetaxel and ritonavir (to understand the mechanism of the drug-drug interaction more thoroughly)
Time frame: Sampling at baseline, the analyses will be performed retrospectively
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2021.
- Derived from this study: PubMed 33464545Vermunt MAC, de Weger VA, Janssen JM, Lopez-Yurda MI, Keessen M, Thijssen B, Rosing H, Huitema ADR, Beijnen JH, Marchetti S. Effect of Food on the Pharmacokinetics of the Oral Docetaxel Tablet Formulation ModraDoc006 Combined with Ritonavir (ModraDoc006/r) in Patients with Advanced Solid Tumours. Drugs R D. 2021 Mar;21(1):103-111. doi: 10.1007/s40268-020-00336-x. Epub 2021 Jan 19.
- 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 11 inclusion and 12 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: finished, as of the sponsor's last update on 19 Oct 2021. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 AUC of docetaxel (area under the curve) (time frame: Pharmacokinetic sampling during 2 weeks, 0-48 hours after administration (i.e. the 2 treatment cycles)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03147378, which also lists 1 linked publication.
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 19 Oct 2021.