Prostatic NeoplasmsPhase 1DOPNCT03066154
Oral Docetaxel (ModraDoc/r) in Combination With Hormonal Treatment and Radiation Therapy in High-risk Prostate Cancer
A Phase 1 study testing oral docetaxel (ModraDoc/r), androgen deprivation therapy and high-dose intensity-modulated radiation therapy in people with Prostatic Neoplasms, run by The Netherlands Cancer Institute at 1 site in Netherlands.
Trial summary
The optimal treatment for HRPC patients has not yet been established. Recent trials suggest a benefit from early treatment with docetaxel in the castration-sensitive setting, with an improvement in failure free survival in high risk and metastatic patients and increase in overall survival in the metastatic… Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostatic Neoplasms
- What is being tested?
- oral docetaxel (ModraDoc/r), androgen deprivation therapy and high-dose intensity-modulated radiation therapy
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteNetherlands
- Study dates
- Sep 2016to Aug 2022
- 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
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically proven prostate cancer.
- All eligible patients have hormone naïve non-metastatic node positive high risk prostate cancer. Node positive cancer will be defined as radiological demonstration of more than four pelvic lymph node(s) consisting of bean shaped lymph node(s) with a short axis of minimal 10 mm and/or round lymph node(s) with a minimal size of 8 mm on PSMA, MRI or CT scan.
- PSMA-scans or PET-Choline scans may be used, but are not obligated. Since the use of the PSMA scan is significantly increased in current clinical practice and the chance of false positive results is considered very low in patients with more than 4 positive lymph nodes, histological confirmation of positive lymph nodes is not required for inclusion if more than 4 pathological nodes are seen with the PSMA, MRI or CT scan
- High risk prostate cancer will be defined as node positive with all of the following primary tumour characteristics: Tumour stage ≥cT2c and Gleason score ≥4+3, any PSA
- Age ≥ 18 years
- No signs of metastatic disease on standard diagnostic scans.
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- Normal serum testosterone levels prior to treatment
- Adequate haematological, renal and hepatic functions
- Haemoglobin ≥ 6.0 mmol/l
- 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).
- WHO performance status of 0-2
- Able and willing to undergo blood sampling for PK and PD analysis;
- Life expectancy ≥ 3 months allowing adequate follow up of toxicity evaluation and antitumor activity;
- Able and willing to swallow oral medication
- Able and willing to give written informed consent;
Who cannot join
- Any treatment with investigational drugs, chemotherapy or immunotherapy within 30 days prior to receiving the first dose of investigational treatment; Patients may be on ADT as long as this is has not been longer than 4 weeks prior the start of the radiotherapy.
- Patients who have had prior pelvic radiation therapy
- Patients who have had prior treatment with taxanes
- TURP within 3 months before start of the study
- Patients who have had a prostatectomy.
- Any contra-indication for MRI
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- Major difficulties for marker implantation
- Unreliable contraceptive methods. Men enrolled in this trial must agree to use a reliable contraceptive method throughout the study (adequate contraceptive methods are: condom, sterilization)
- Unresolved (> grade 1) toxicities of previous chemotherapy, excluding alopecia.
- Uncontrolled infectious disease or known Human Immunodeficiency Virus HIV-1 or HIV-2 type patients;
- Patients with a known history of hepatitis B or C;
- Bowel obstructions or motility disorders that may influence the resorption of drugs as judged by the treating physician
- Concomitant use of MDR and CYP3A modulating drugs such as Ca+- entry blockers (verapamil, dihydropyridines), cyclosporine, quinidine, tamoxifen, megestrol and grapefruit juice, concomitant use of HIV medications, other protease inhibitors, (non) nucleoside analoga, or St. John's wort.
- Pre-existing neuropathy greater than NCI-CTCAE v4.03 grade 1.
- Patients with known alcoholism, drug addiction and/or psychiatric of physiological condition which in the opinion of the investigator would impair study compliance; 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.
About this study
Official title: Weekly ModraDoc/r in Combination With Hormonal Treatment and High-dose Intensity-modulated Radiation Therapy in Patients With High-risk Early Stage Prostate Cancer
The optimal treatment for HRPC patients has not yet been established. Recent trials suggest a benefit from early treatment with docetaxel in the castration-sensitive setting, with an improvement in failure free survival in high risk and metastatic patients and increase in overall survival in the metastatic hormone-sensitive group. In these recent randomized controlled trials, patients were treated with hormonal therapy and radiotherapy and adjuvant docetaxel, assuming that early systemic treatment for high risk or metastatic disease could delay progression in patients with aggressive primary tumor characteristics.
With the fact that docetaxel is a known radiosensitizer, combined modality treatment with docetaxel during the radiotherapy could also lead to better local control and reduction of local recurrence. Several phase I and II studies have been done in HRPC patients, to evaluate the combination of high dose radiotherapy and concurrent weekly infusions with docetaxel.
Read more
Oral administration of docetaxel has many advantages above intravenously administered drugs for patients. Besides the higher patient convenience, possibly longer treatment duration can be achieved due to better safety. Frequently occurring toxicities of intravenously administered docetaxel, such as neutropenia, hypersensitivity reactions and peripheral polyneuropathy have rarely been observed with the oral docetaxel formulation ModraDoc006/r.
The primary aim of the N15DOP study is to determine the maximum tolerable dose (MTD) of ModraDoc006/r when given in a weekly bidaily schedule in combined modality with high dose intensity radiotherapy and hormonal therapy in castration-sensitive prostate cancer patients with high risk disease, including positive lymph nodes.
Read the detailed description
Phase IA part This is an open-label, dose-escalating, non-randomized, single centre phase I study of ModraDoc006/r combined with ADT and radiotherapy in patients with high risk prostate cancer, as defined by node positive prostate cancer with all of the following primary tumor characteristics: stage ≥cT2c, Gleason score ≥ 4+3, any PSA level.
Phase IB part After determination of the MTD of ModraDoc006/r in the combined treatment with radiotherapy and hormonal therapy and good tolerability of the treatment without unexpected adverse events during the radiotherapy until 6 weeks after the end of radiotherapy, the study will be further conducted to the phase IB part. This part will explore the feasibility and tolerability of long term treatment with ModraDoc006/r.
- Conditions
- Prostatic Neoplasms
- Being tested
- oral docetaxel (ModraDoc/r), androgen deprivation therapy, high-dose intensity-modulated radiation therapy
- Keywords
- High risk prostate cancer, >T2cN+M0
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
oral docetaxel (ModraDoc/r)Drug
Also called ModraDoc006/ritonavir
Weekly once- or twice daily ModraDoc/r
androgen deprivation therapyDrug
Also called hormonal therapy
ADT according to the standard of care
high-dose intensity-modulated radiation therapyRadiation
Also called radiotherapy
77 Gy in 35 fractions of 2.2 Gy, 5 fractions a week
| Study group | Role | What they receive |
|---|---|---|
| N15DOP | Experimental | Chemoradiation with ModraDoc/r and radiotherapy of the prostate in dose escalation design, followed by maintenance treatment. Receives: Drug: oral docetaxel (ModraDoc/r); Drug: androgen deprivation therapy; Radiation: high-dose intensity-modulated radiation therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximal tolerated dose (MTD) of ModraDoc/r in the combination treatment
MTD of ModraDoc006/r (as ModraDoc006 10 mg tablets in combination with one tablet of 100 mg ritonavir) that can safely be administered in a bi-daily weekly schedule in combination with high-dose intensity modulated radiation therapy and androgen-deprivation therapy
Measured: 12 months
Secondary outcomes (4)
Number of participants with treatment-related adverse events as assessed by CTCAE v.4.03 with treatment with ModraDoc006/r in combination with ADT and high dose radiotherapy
Number of participants with treatment-related adverse events as assessed by CTCAE
Measured: 12 months
Number of patients that will have recurrence of prostate cancer after completion of the study treatment
Number of patients that will have recurrence of prostate cancer after completion of the study treatment
Measured: 10 years
Peak Plasma Concentration (Cmax) of docetaxel in this regime.
Peak Plasma Concentration (Cmax) of docetaxel in this regime.
Measured: 12 months
Area under the plasma concentration versus time curve (AUC) of docetaxel in this regime.
Area under the plasma concentration versus time curve (AUC) of docetaxel in this regime.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2017
- Study startSep 2016
- Primary completionFeb 2022
- Study completionAug 2022
Why it stopped: low inclusion of patients and availability of the IP
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 Prostatic NeoplasmsStudies of the same condition, open and under way.
- More trials run by The Netherlands Cancer InstituteThe sponsor's other registered studies.
- 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
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Netherlands Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- B van Triest, MD, PhD, Principal investigator, The Netherlands Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03066154
- Sponsor's protocol ID
- N15DOP
- Acronym
- DOP
- Status last verified
- May 2024
- First submitted
- 23 Sep 2016
- Last updated
- 3 Jun 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Vermunt MAC, van der Heijden LT, Hendrikx JJMA, Schinkel AH, de Weger VA, van der Putten E, van Triest B, Bergman AM, Beijnen JH. Pharmacokinetics of docetaxel and ritonavir after oral administration of ModraDoc006/r in patients with prostate cancer versus patients with other advanced solid tumours. Cancer Chemother Pharmacol. 2021 Jun;87(6):855-869. doi: 10.1007/s00280-021-04259-5. Epub 2021 Mar 20.
PubMed 33744986
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Weekly ModraDoc/r in Combination With Hormonal Treatment and High-dose Intensity-modulated Radiation Therapy in Patients With High-risk Early Stage Prostate Cancer
- ClinicalTrials.gov ID
- NCT03066154
- Acronym / sponsor ID
- DOP / N15DOP
- Conditions
- Prostatic Neoplasms
- Keywords
- High risk prostate cancer, >T2cN+M0
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: low inclusion of patients and availability of the IP
- Enrolment
- 24 participants (actual)
- Lead sponsor
- The Netherlands Cancer InstituteUniversity, hospital or other
- Study start
- Sep 2016 (actual)
- Primary completion
- Feb 2022 (actual)
- Study completion
- Aug 2022 (actual)
- First posted
- 28 Feb 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.
The optimal treatment for HRPC patients has not yet been established. Recent trials suggest a benefit from early treatment with docetaxel in the castration-sensitive setting, with an improvement in failure free survival in high risk and metastatic patients and increase in overall survival in the metastatic hormone-sensitive group. In these recent randomized controlled trials, patients were treated with hormonal therapy and radiotherapy and adjuvant docetaxel, assuming that early systemic treatment for high risk or metastatic disease could delay progression in patients with aggressive primary tumor characteristics.
With the fact that docetaxel is a known radiosensitizer, combined modality treatment with docetaxel during the radiotherapy could also lead to better local control and reduction of local recurrence. Several phase I and II studies have been done in HRPC patients, to evaluate the combination of high dose radiotherapy and concurrent weekly infusions with docetaxel.
Oral administration of docetaxel has many advantages above intravenously administered drugs for patients. Besides the higher patient convenience, possibly longer treatment duration can be achieved due to better safety. Frequently occurring toxicities of intravenously administered docetaxel, such as neutropenia, hypersensitivity reactions and peripheral polyneuropathy have rarely been observed with the oral docetaxel formulation ModraDoc006/r.
The primary aim of the N15DOP study is to determine the maximum tolerable dose (MTD) of ModraDoc006/r when given in a weekly bidaily schedule in combined modality with high dose intensity radiotherapy and hormonal therapy in castration-sensitive prostate cancer patients with high risk disease, including positive lymph nodes.
Detailed description
Phase IA part This is an open-label, dose-escalating, non-randomized, single centre phase I study of ModraDoc006/r combined with ADT and radiotherapy in patients with high risk prostate cancer, as defined by node positive prostate cancer with all of the following primary tumor characteristics: stage ≥cT2c, Gleason score ≥ 4+3, any PSA level.
Phase IB part After determination of the MTD of ModraDoc006/r in the combined treatment with radiotherapy and hormonal therapy and good tolerability of the treatment without unexpected adverse events during the radiotherapy until 6 weeks after the end of radiotherapy, the study will be further conducted to the phase IB part. This part will explore the feasibility and tolerability of long term treatment with ModraDoc006/r.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| N15DOP | Experimental | Drug: oral docetaxel (ModraDoc/r), Drug: androgen deprivation therapy, Radiation: high-dose intensity-modulated radiation therapyChemoradiation with ModraDoc/r and radiotherapy of the prostate in dose escalation design, followed by maintenance treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Histologically proven prostate cancer.
- All eligible patients have hormone naïve non-metastatic node positive high risk prostate cancer. Node positive cancer will be defined as radiological demonstration of more than four pelvic lymph node(s) consisting of bean shaped lymph node(s) with a short axis of minimal 10 mm and/or round lymph node(s) with a minimal size of 8 mm on PSMA, MRI or CT scan.
- PSMA-scans or PET-Choline scans may be used, but are not obligated. Since the use of the PSMA scan is significantly increased in current clinical practice and the chance of false positive results is considered very low in patients with more than 4 positive lymph nodes, histological confirmation of positive lymph nodes is not required for inclusion if more than 4 pathological nodes are seen with the PSMA, MRI or CT scan
- High risk prostate cancer will be defined as node positive with all of the following primary tumour characteristics: Tumour stage ≥cT2c and Gleason score ≥4+3, any PSA
- Age ≥ 18 years
Key exclusion criteria (16 listed)
- Any treatment with investigational drugs, chemotherapy or immunotherapy within 30 days prior to receiving the first dose of investigational treatment; Patients may be on ADT as long as this is has not been longer than 4 weeks prior the start of the radiotherapy.
- Patients who have had prior pelvic radiation therapy
- Patients who have had prior treatment with taxanes
- TURP within 3 months before start of the study
- Patients who have had a prostatectomy.
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 |
|---|---|---|
| oral docetaxel (ModraDoc/r)Also: ModraDoc006/ritonavirWeekly once- or twice daily ModraDoc/r | Drug | N15DOP |
| androgen deprivation therapyAlso: hormonal therapyADT according to the standard of care | Drug | N15DOP |
| high-dose intensity-modulated radiation therapyAlso: radiotherapy77 Gy in 35 fractions of 2.2 Gy, 5 fractions a week | Radiation | N15DOP |
Primary outcome
Maximal tolerated dose (MTD) of ModraDoc/r in the combination treatment
Time frame: 12 months
MTD of ModraDoc006/r (as ModraDoc006 10 mg tablets in combination with one tablet of 100 mg ritonavir) that can safely be administered in a bi-daily weekly schedule in combination with high-dose intensity modulated radiation therapy and androgen-deprivation therapy
4 secondary outcomes
Number of participants with treatment-related adverse events as assessed by CTCAE v.4.03 with treatment with ModraDoc006/r in combination with ADT and high dose radiotherapy
Time frame: 12 months
Number of patients that will have recurrence of prostate cancer after completion of the study treatment
Time frame: 10 years
Peak Plasma Concentration (Cmax) of docetaxel in this regime.
Time frame: 12 months
Area under the plasma concentration versus time curve (AUC) of docetaxel in this regime.
Time frame: 12 months
Results and safety
The study was stopped early (reason given: low inclusion of patients and availability of the IP). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2024.
- Derived from this study: PubMed 33744986Vermunt MAC, van der Heijden LT, Hendrikx JJMA, Schinkel AH, de Weger VA, van der Putten E, van Triest B, Bergman AM, Beijnen JH. Pharmacokinetics of docetaxel and ritonavir after oral administration of ModraDoc006/r in patients with prostate cancer versus patients with other advanced solid tumours. Cancer Chemother Pharmacol. 2021 Jun;87(6):855-869. doi: 10.1007/s00280-021-04259-5. Epub 2021 Mar 20.
- 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.
B van Triest, 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 oral docetaxel (ModraDoc/r), androgen deprivation therapy and high-dose intensity-modulated radiation therapy in people with Prostatic Neoplasms, run by The Netherlands Cancer Institute 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 18 inclusion and 16 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: stopped early, as of the sponsor's last update on 3 Jun 2024. 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 stopped early (reason given: low inclusion of patients and availability of the IP). Results are not available in the source record.
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?
Maximal tolerated dose (MTD) of ModraDoc/r in the combination treatment (time frame: 12 months). 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 NCT03066154, 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 3 Jun 2024.