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This is a multicenter phase 2b study to evaluate the efficacy and tolerability of ModraDoc006 in combination with ritonavir (denoted ModraDoc006/r) in patients with metastatic castration-resistant prostate cancer, suitable for treatment with a taxane.
This is an open label 1:1 randomized Phase 2b trial to determine the efficacy and tolerability of oral ModraDoc006/r versus i.v. docetaxel in mCRPC subjects. Cohort 1 will receive i.v. docetaxel at 75 mg/m2 every 3 weeks (Q3W). Cohort 2 will receive 30 mg ModraDoc006 in combination with 200 mg ritonavir in the morning and 20 mg ModraDoc006 in combination with 100 mg ritonavir in the evening (7-12 hours after the morning dose), on Day 1, 8 and 15 of a 21-day cycle (BIDW). All patients will also receive 5 mg oral prednisone twice daily. Treatment in both cohorts will continue until disease progression, unacceptable toxicity, or discontinuation for any other reason. The end of the trial is defined as the time point when all subjects have discontinued trial treatment and have been given follow-up for safety measurements according to the trial assessment schedule.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Docetaxel IV | Active Comparator | This study arm will receive docetaxel at 75 mg/m2 given i.v. as a one-hour infusion on day 1 every 21 days plus 5 mg oral prednisone twice daily. |
|
| ModraDoc006/r | Experimental | This cohort will receive ModraDoc006/r 30 mg oral docetaxel in combination with 200 mg ritonavir in the morning and 20 mg oral docetaxel in combination with 100 mg ritonavir in the evening (7-12 hours after the morning dose), on Day 1, 8 and 15 of a 21-day cycle, plus 5 mg oral prednisone twice daily. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Docetaxel in Parenteral Dosage Form | Drug | Treatment with IV docetaxel at 75 mg/m2 given as a one-hour infusion on day 1 every 21 days plus 5 mg oral prednisone twice daily |
|
| Measure | Description | Time Frame |
|---|---|---|
| Radiographic Progression Free Survival (rPFS) | Evaluation of rPFS that will be observed as measured by Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria, in patients with metastatic prostate cancer after treatment with ModraDoc006/r or docetaxel IV. Radiographic disease progression was defined by the local assessment of:
| Time from the date of randomization to the date of the first radiologic progression (per PCWG3 criteria) or death from any cause, whichever occurred first, an average of 1 year. |
| Measure | Description | Time Frame |
|---|---|---|
| Adverse Event Profile (Safety) | The hematological and non-hematological safety profile of ModraDoc006/r will be assessed by clinical and laboratory evaluations according to CTCAE v5.0. | Evaluation of all adverse events during the complete study treatment until 28 days after the last intake, an average of 1 year. |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Health-Related Quality of Life Response | An overall Health-Related Quality of Life (HRQoL) improvement was defined by a 10-point or greater increase (= lower score) in the Functional Assessment of Cancer Therapy-global (FACT-G) total score assessment at a post-baseline assessment compared with baseline, at least once during the study. The FACT-G questionnaire contains 27-items to measure four domains of HRQoL on a 5 point Likert-type scale in cancer patients: Physical Well-Being (7 items; score range 0-28), Social/Family Well-Being (7 items; score range 0-28), Emotional Well-Being (6 items; score range 0-24), Functional Well-Being (7 items; score range 0-28). Higher scores and increases from baseline indicate higher quality of life. |
Inclusion Criteria:
Age ≥ 18 years
Histologically or cytologically proven prostate cancer with evidence of progressive mCRPC, defined as:
Measurable tumour lesions, defined as pelvic and/or extra-pelvic nodal lesions ≥1.5 cm in the short axis or visceral lesions ≥1.0 cm in the longest dimensions and measurable according to RECIST v1.1, bone metastasis as evaluated with 99mTc-methylene diphosphonate (MDP) radionuclide bone scintigraphy
Resolution of toxicity of prior therapy to < grade 2 (except for alopecia), as defined by CTCAE v5.0
Adequate haematological, renal and hepatic functions:
World Health Organisation Performance Status (WHO-PS) of 0-2
Estimated life expectancy of at least 12 weeks
Able and willing to swallow oral medication
Able and willing to undergo radiologic scans (CT scan)
Able and willing to give written informed consent according to local guidelines
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| M Keessen, MSc, MBA | Modra Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Karmanos Cancer Institute | Detroit | Michigan | 48201 | United States | ||
| Comprehensive Cancer Centers of Nevada |
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The number of enrollment is not equal to the number of patients started, because 32 patients did not meet the inclusion criteria.
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| ID | Title | Description |
|---|---|---|
| FG000 | Docetaxel IV | In this study arm patients received docetaxel at 75 mg/m2 given i.v. as a one-hour infusion on day 1 every 21 days (Q3W), plus 5 mg oral prednisone twice daily. Premedication with dexamethasone was required. Docetaxel in Parenteral Dosage Form: Treatment with IV docetaxel at 75 mg/m2 given as a one-hour infusion on day 1 every 21 days plus 5 mg oral prednisone twice daily. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 31, 2020 | Jan 9, 2024 |
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One-hundred RECIST 1.1 evaluable patients will be randomized 1:1 to treatment with ModraDoc006/r versus standard i.v. docetaxel. The treatment outcome will be estimated and used as the basis for the design of the future pivotal phase 3 trial. The sample size of 50 evaluable patients per cohort will provide a sufficiently precise point estimate of the primary endpoint radiographic Progression Free Survival (rPFS) in both groups to calculate the sample size for the pivotal study.
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| ModraDoc006/r | Drug | Treatment with twice daily once weekly (BIDW) ModraDoc006 (oral docetaxel) 10mg tablets in combination with ritonavir 100mg tablets |
|
|
| Overall Response Rate (ORR) |
Percentage of patients evaluable for radiological response (ERR) per Prostate Cancer Working Group 3 (PCWG3)-modified Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT/MRI with best overall response of either Complete Response (CR), i.e. disappearance of all target lesions, or Partial Response (PR), i.e. ≥30% decrease in the sum of the longest diameter of target lesions. PCGW3-modified RECIST 1.1 criteria implements the requirement for confirmation of progression at least 6 weeks later for bone lesions at all measurement time points, and for soft tissue lesions after the first measurement (after 2 months) only. Tumor measurements were scheduled after every 8 treatment weeks for the first 24 weeks (i.e. during Week 9, Week 17 and Week 25) and every 12 weeks thereafter. |
| From baseline during the complete study treatment, including follow-up visit 28 days after the last treatment, an average of 1 year. |
| Disease Control Rate (DCR) | Disease control rate is calculated by the percentage of patients with Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), ≥30% decrease in the sum of the longest diameter of target lesions; and Stable Disease (SD), ≤20% increase to <30% decrease in the sum of the longest diameter of target lesions per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT/MRI. Disease control rate is presented by treatment group for patients that were evaluable for radiological response for the overall study. | From baseline through study completion, an average of 1 year |
| Duration of Response (DOR) | DOR is defined as the median time in months from documentation of first tumor response to the first objective evidence of radiologic progression, as measured per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT/MRI, in the subpopulation of patients experiencing a Complete Response (CR), i.e. Disappearance of all target lesions; and Partial Response (PR), i.e. ≥30% decrease in the sum of the longest diameter of target lesions. | From baseline through study completion, an average of 1 year |
| Time to Progression (TTP) | Time to Progression is defined as the time from the date of randomization to the date of the first radiologic progression per PCWG3 criteria. | Time from the date of randomization to the date of the first radiologic progression, an average of 1 year. |
| PSA Response Rate | PSA decline of >50% from baseline with confirmatory read ≥3 weeks later, based on the Prostate Cancer Working Group 3 (PCWG3) criteria recommendations. | From baseline through study completion, an average of 1 year |
| PSA-PFS | Prostate-Specific Antigen Progression-Free Survival (PSA-PFS) according to Prostate Cancer Working Group 3 (PCWG3) guidance. Prostate-specific antigen progression was defined as per PCWG3 guidance:
| Time from the date of randomization to the date of the first prostate-specific antigen progression or death from any cause, whichever occurred first, an average of 1 year. |
| Time to PSA Progression | Time to PSA progression was defined as the time from the date of randomization to the PSA progression as defined by Prostate Cancer Working Group 3 (PCWG3). Prostate-specific antigen progression was defined as per PCWG3 guidance:
| From baseline through study completion, an average of 1 year |
| Number of Participants Who Experienced a First Skeletal-Related Event | Number of Participants who Experienced a first Skeletal-Related Event (SRE), i.e. the occurrence of the first skeletal-related event (i.e. radiation therapy or surgery to bone, clinically apparent pathological bone fracture, spinal cord compression, or change of antineoplastic therapy to treat bone pain); from the time of randomisation to the first occurrence. Note: Due to small number of SREs the median time to SRE was not evaluable in this patient population. | From baseline through study completion, an average of 1 year |
| From baseline through to end of Cycle 10 (each cycle was 21 days) |
| Summary of Improvement by Individual Health- Related Quality of Life Domains | Improvement for individual patients in Health-Related Quality of Life (HRQoL) domains was defined by a ≥3-point increase in the score of a 5 point Likert-like scale at a post-baseline assessment compared with baseline, at least once during study for Functional Assessment of Cancer Therapy (FACT)-G, -P and -T. Improvement was derived using all assessments collected per protocol schedule, i.e. Baseline, End of Cycle 3, 6 and 10 (or End of Treatment if sooner). Higher scores represent better HRQoL. FACT-G = global scale, measures four domains of HRQoL in cancer patients: Physical Well-Being (7 items; score range 0-28), Social/Family Well-Being (7 items; range 0-28), Emotional Well-Being (6 items; range 0-24), Functional Well-Being (7 items; range 0-28). Total score (range 0-108) FACT-P = prostate cancer sub scale (12 items; score range 0-48). Total score (FACT-G total score + FACT-P), range 0-156) FACT-T = taxane specific domain score (16 items, range 0 to 64), Total score (0-172) | Improvement assessed at any timepoint from baseline through to End of Cycle 10 (each cycle was 21 days) |
| Overall Health-Related Utility | Mean change from baseline to the End of Cycle 10 in the European Quality of Life Dimension-Five Level Scale (EQD5) is presented. For the EQD5, mobility, self-care, usual activities, pain/discomfort, and anxiety/depression were scored on a 5-point scale: no problems (1), slight problems (2), moderate problems (3), severe problems (4), and extreme problems (5). Lower scores and decreases from baseline indicate improved quality of life. A visual analog scale (VAS) was used for the patient to evaluate their health state at a particular visit; the scale was numbered from 0 (representing the worst health imaginable) to 100 (representing the best health imaginable), higher scores and increases from baseline indicate improved health. | Assessed from baseline to End of Cycle 10 (each cycle was 21 days) |
| World Health Organization Performance Status (Eastern Cooperative Oncology Group) at End of Treatment | Eastern Cooperative Oncology Group (ECOG) scores at the time of end on treatment visit are presented. 0 = Normal activity
| Score assessed at end of treatment visit (up to 2 years). |
| Las Vegas |
| Nevada |
| 89119 |
| United States |
| Providence Cancer Institute | Portland | Oregon | 97213 | United States |
| Carolina Urologic Research Center | Myrtle Beach | South Carolina | 29572 | United States |
| Nemocnice Liberec | Liberec | Czechia |
| Urologicke oddeleni FTN | Prague | Czechia |
| Universitätsmedizin Göttingen | Göttingen | Germany |
| Studienpraxis Urologie | Nürtingen | Germany |
| Universitätsklinikum Tübingen | Tübingen | Germany |
| Orszagos Onkologiai Intezet (National Institute of Oncology) | Budapest | 6000 | Hungary |
| Debreceni Egyetem Klinikai Központ | Debrecen | Hungary |
| Petz Aladár Megyei Oktató Kórház | Győr | Hungary |
| Jasz-Nagykun-Szolnok Megyei - Hetenyi Geza Korhaz - Rendelointezet - Onkologiai Kozpont | Szolnok | 9700 | Hungary |
| Przychodnia Lekarska "KOMED" | Konin | Poland |
| Instytut Centrum Zdrowia Matki Polki | Lodz | Poland |
| Centrum Onkologii - Instytut im. Marii Skłodowskiej-Curie | Warsaw | Poland |
| Regional State Budgetary Healthcare Institution "Altai regional oncology dispensary" | Barnaul | Russia |
| Limited Liability Company "EVIMED | Chelyabinsk | Russia |
| Regional State Budget Institution "Krasnoyarsk Territorial Clinical Hospital n.a. A.I.Kryzhanovskogo" | Krasnoyarsk | Russia |
| Federal State Institution "Russian Cancer Research Center named after N. N. Blokhin" RAMS | Moscow | Russia |
| CJSC Medical Center "AVICENNA" | Novosibirsk | Russia |
| Federal state budget institution "National medical research radiological center " of the Ministry of healthcare of the Russian Federation, branch - A. Tsyb Medical Radiological Research Center | Obninsk | Russia |
| Clinical Oncological Dispensary of Omsk Region | Omsk | Russia |
| Leningrad Region Onco Dispensary | Saint Petersburg | Russia |
| Limited Liability Company "Klinika Andros [Andros Clinic]" | Saint Petersburg | Russia |
| National medical research center of oncology n.a. N.N. Petrov | Saint Petersburg | Russia |
| Pavlov First Saint Petersburg State Medical University | Saint Petersburg | Russia |
| Sverdlovsk Regional Clinical Hospital No. 1 | Yekaterinburg | Russia |
| FG001 | ModraDoc006/r | In this study arm patients initially received ModraDoc006 30 mg in combination with ritonavir 200 mg in the morning and ModraDoc006 20 mg in combination with 100 mg ritonavir in the afternoon, 7 to 12 hours after the morning dose (=ModraDoc006/r 30-20/200-100 mg) twice daily once weekly (BIDW) on Days 1, 8, and 15 of a 21-day cycle, plus prednisone 5 mg orally twice daily. After a total of 39 patients randomized (21 patients in ModraDoc006/r), the morning dose was amended to 20 mg in combination with ritonavir 200 mg (=ModraDoc006/r 20-20/200-100 mg). No dexamethasone premedication was given. ModraDoc006/r: Treatment with twice daily once weekly (BIDW) ModraDoc006 (oral docetaxel) 10mg tablets in combination with ritonavir 100mg tablets. |
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| NOT COMPLETED |
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Baseline characteristics have been provided for the Full Analysis Set (FAS). All patients who received at least 1 dose of intravenous docetaxel (Cohort 1) or 1 full cycle of ModraDoc006/r (Cohort 2) and had at least 1 post-baseline tumor assessment were included in the FAS.
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| ID | Title | Description |
|---|---|---|
| BG000 | Docetaxel IV | Patients received docetaxel at 75 mg/m2 i.v. Q3W, with dexamethasone premedication, plus 5 mg oral prednisone twice daily. |
| BG001 | ModraDoc006/r | Patients received ModraDoc006/r either at 30-20/200-100 mg or at 20-20/200-100 mg BIDW, plus 5 mg oral prednisone twice daily. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| ECOG Performance Status at study entry | Count of Participants | Participants |
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| Time since diagnosis of mCRPC | Mean | Standard Deviation | Months |
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| RECIST measurable disease at study entry | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Radiographic Progression Free Survival (rPFS) | Evaluation of rPFS that will be observed as measured by Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria, in patients with metastatic prostate cancer after treatment with ModraDoc006/r or docetaxel IV. Radiographic disease progression was defined by the local assessment of:
| All patients who received at least 1 dose of intravenous docetaxel (Cohort 1) or 1 full cycle of ModraDoc006/r (Cohort 2) and had at least 1 post-baseline tumor assessment were included in the Full Analysis Set (FAS). All patients with an rPFS event. | Posted | Median | 95% Confidence Interval | Months | Time from the date of randomization to the date of the first radiologic progression (per PCWG3 criteria) or death from any cause, whichever occurred first, an average of 1 year. |
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| Secondary | Adverse Event Profile (Safety) | The hematological and non-hematological safety profile of ModraDoc006/r will be assessed by clinical and laboratory evaluations according to CTCAE v5.0. | The Safety Population (SAF) was used for the evaluation of safety. All patients receiving at least 1 dose of trial medication in either study arm were included in the SAF. | Posted | Count of Participants | Participants | Evaluation of all adverse events during the complete study treatment until 28 days after the last intake, an average of 1 year. |
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| Secondary | Overall Response Rate (ORR) | Percentage of patients evaluable for radiological response (ERR) per Prostate Cancer Working Group 3 (PCWG3)-modified Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT/MRI with best overall response of either Complete Response (CR), i.e. disappearance of all target lesions, or Partial Response (PR), i.e. ≥30% decrease in the sum of the longest diameter of target lesions. PCGW3-modified RECIST 1.1 criteria implements the requirement for confirmation of progression at least 6 weeks later for bone lesions at all measurement time points, and for soft tissue lesions after the first measurement (after 2 months) only. Tumor measurements were scheduled after every 8 treatment weeks for the first 24 weeks (i.e. during Week 9, Week 17 and Week 25) and every 12 weeks thereafter. | Population evaluable for radiological response (ERR). Patients with measurable lesions according to RECIST v1.1, that have received at least 6 weekly administrations of ModraDoc006/r or 2 standard three-weekly cycles of i.v. docetaxel were included. Response was evaluated according to RECIST v1.1 and PCWG3 criteria. | Posted | Number | 95% Confidence Interval | Percentage of participants analyzed | From baseline during the complete study treatment, including follow-up visit 28 days after the last treatment, an average of 1 year. |
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| Secondary | Disease Control Rate (DCR) | Disease control rate is calculated by the percentage of patients with Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), ≥30% decrease in the sum of the longest diameter of target lesions; and Stable Disease (SD), ≤20% increase to <30% decrease in the sum of the longest diameter of target lesions per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT/MRI. Disease control rate is presented by treatment group for patients that were evaluable for radiological response for the overall study. | Population evaluable for radiological response (ERR). | Posted | Number | 95% Confidence Interval | Percentage of participants analyzed | From baseline through study completion, an average of 1 year |
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| Secondary | Duration of Response (DOR) | DOR is defined as the median time in months from documentation of first tumor response to the first objective evidence of radiologic progression, as measured per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT/MRI, in the subpopulation of patients experiencing a Complete Response (CR), i.e. Disappearance of all target lesions; and Partial Response (PR), i.e. ≥30% decrease in the sum of the longest diameter of target lesions. | Population evaluable for radiological response (ERR). | Posted | Median | 95% Confidence Interval | Months | From baseline through study completion, an average of 1 year |
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| Secondary | Time to Progression (TTP) | Time to Progression is defined as the time from the date of randomization to the date of the first radiologic progression per PCWG3 criteria. | Full Analysis Set | Posted | Median | 95% Confidence Interval | Months | Time from the date of randomization to the date of the first radiologic progression, an average of 1 year. |
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| Secondary | PSA Response Rate | PSA decline of >50% from baseline with confirmatory read ≥3 weeks later, based on the Prostate Cancer Working Group 3 (PCWG3) criteria recommendations. | Full Analysis Set | Posted | Count of Participants | Participants | From baseline through study completion, an average of 1 year |
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| Secondary | PSA-PFS | Prostate-Specific Antigen Progression-Free Survival (PSA-PFS) according to Prostate Cancer Working Group 3 (PCWG3) guidance. Prostate-specific antigen progression was defined as per PCWG3 guidance:
| Full Analysis Set | Posted | Median | 95% Confidence Interval | Months | Time from the date of randomization to the date of the first prostate-specific antigen progression or death from any cause, whichever occurred first, an average of 1 year. |
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| Secondary | Time to PSA Progression | Time to PSA progression was defined as the time from the date of randomization to the PSA progression as defined by Prostate Cancer Working Group 3 (PCWG3). Prostate-specific antigen progression was defined as per PCWG3 guidance:
| Full Analysis Set | Posted | Median | 95% Confidence Interval | Months | From baseline through study completion, an average of 1 year |
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| Secondary | Number of Participants Who Experienced a First Skeletal-Related Event | Number of Participants who Experienced a first Skeletal-Related Event (SRE), i.e. the occurrence of the first skeletal-related event (i.e. radiation therapy or surgery to bone, clinically apparent pathological bone fracture, spinal cord compression, or change of antineoplastic therapy to treat bone pain); from the time of randomisation to the first occurrence. Note: Due to small number of SREs the median time to SRE was not evaluable in this patient population. | Full Analysis Set | Posted | Number | participants | From baseline through study completion, an average of 1 year |
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| Other Pre-specified | Overall Health-Related Quality of Life Response | An overall Health-Related Quality of Life (HRQoL) improvement was defined by a 10-point or greater increase (= lower score) in the Functional Assessment of Cancer Therapy-global (FACT-G) total score assessment at a post-baseline assessment compared with baseline, at least once during the study. The FACT-G questionnaire contains 27-items to measure four domains of HRQoL on a 5 point Likert-type scale in cancer patients: Physical Well-Being (7 items; score range 0-28), Social/Family Well-Being (7 items; score range 0-28), Emotional Well-Being (6 items; score range 0-24), Functional Well-Being (7 items; score range 0-28). Higher scores and increases from baseline indicate higher quality of life. | Full Analysis Set | Posted | Count of Participants | Participants | From baseline through to end of Cycle 10 (each cycle was 21 days) |
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| Other Pre-specified | Summary of Improvement by Individual Health- Related Quality of Life Domains | Improvement for individual patients in Health-Related Quality of Life (HRQoL) domains was defined by a ≥3-point increase in the score of a 5 point Likert-like scale at a post-baseline assessment compared with baseline, at least once during study for Functional Assessment of Cancer Therapy (FACT)-G, -P and -T. Improvement was derived using all assessments collected per protocol schedule, i.e. Baseline, End of Cycle 3, 6 and 10 (or End of Treatment if sooner). Higher scores represent better HRQoL. FACT-G = global scale, measures four domains of HRQoL in cancer patients: Physical Well-Being (7 items; score range 0-28), Social/Family Well-Being (7 items; range 0-28), Emotional Well-Being (6 items; range 0-24), Functional Well-Being (7 items; range 0-28). Total score (range 0-108) FACT-P = prostate cancer sub scale (12 items; score range 0-48). Total score (FACT-G total score + FACT-P), range 0-156) FACT-T = taxane specific domain score (16 items, range 0 to 64), Total score (0-172) | Full Analysis Set | Posted | Count of Participants | Participants | Improvement assessed at any timepoint from baseline through to End of Cycle 10 (each cycle was 21 days) |
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| Other Pre-specified | Overall Health-Related Utility | Mean change from baseline to the End of Cycle 10 in the European Quality of Life Dimension-Five Level Scale (EQD5) is presented. For the EQD5, mobility, self-care, usual activities, pain/discomfort, and anxiety/depression were scored on a 5-point scale: no problems (1), slight problems (2), moderate problems (3), severe problems (4), and extreme problems (5). Lower scores and decreases from baseline indicate improved quality of life. A visual analog scale (VAS) was used for the patient to evaluate their health state at a particular visit; the scale was numbered from 0 (representing the worst health imaginable) to 100 (representing the best health imaginable), higher scores and increases from baseline indicate improved health. | Full Analysis Set | Posted | Mean | Standard Deviation | Change of score on a scale | Assessed from baseline to End of Cycle 10 (each cycle was 21 days) |
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| Other Pre-specified | World Health Organization Performance Status (Eastern Cooperative Oncology Group) at End of Treatment | Eastern Cooperative Oncology Group (ECOG) scores at the time of end on treatment visit are presented. 0 = Normal activity
| Safety population (SAF) | Posted | Count of Participants | Participants | Score assessed at end of treatment visit (up to 2 years). |
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The adverse events were monitored and collected from the time the patient gave informed consent and throughout the study until 30 days after the last ModraDoc006/r or intravenous docetaxel administration; an average of 1 year.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Docetaxel IV | Patients received docetaxel at 75 mg/m2 i.v. Q3W, with dexamethasone premedication, plus 5 mg oral prednisone twice daily. | 4 | 49 | 16 | 49 | 32 | 49 |
| EG001 | ModraDoc006/r | Patients received ModraDoc006/r either at 30-20/200-100 mg or at 20-20/200-100 mg BIDW, plus 5 mg oral prednisone twice daily. | 3 | 52 | 13 | 52 | 37 | 52 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Orthostatic hypotension | Vascular disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Prostate cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (22.0) | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Death | General disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Aphasia | Nervous system disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Hemiparesis | Nervous system disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Dental caries | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Duodenal ulcer | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Peptic ulcer | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Acute hepatic failure | Hepatobiliary disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Hydronephrosis | Renal and urinary disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Urinary retention | Renal and urinary disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Pathological fracture | Musculoskeletal and connective tissue disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Corona virus infection | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Erysipelas | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Escherichia urinary tract infection | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Osteomyelitis | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Pneumonia viral (Covid-19) | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Aspartate aminotransferase increased | Investigations | MedDRA (22.0) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (22.0) | Systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA (22.0) | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA (22.0) | Systematic Assessment |
| |
| Blood lactate dehydrogenase increased | Investigations | MedDRA (22.0) | Systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA (22.0) | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA (22.0) | Systematic Assessment |
| |
| Dypnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Anemia | Blood and lymphatic system disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Hypoaesthesia | Nervous system disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Peripheral swelling | General disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Extravasation | General disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Cystitis noninfective | Renal and urinary disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Nail disorder | Skin and subcutaneous tissue disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (22.0) | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| M. Keessen | Modra Pharmaceuticals | +31202050188 | info@modrapharmaceuticals.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 7, 2021 | Jan 9, 2024 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D000077143 | Docetaxel |
| D007267 | Injections |
| ID | Term |
|---|---|
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D004333 | Drug Administration Routes |
| D004358 | Drug Therapy |
| D013812 | Therapeutics |
Not provided
Not provided
| >=65 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| United States |
|
| Czechia |
|
| Poland |
|
| Germany |
|
| Russia |
|
| Performance status 1 |
|
| Performance status 2 |
|
| No |
|
|
Patients received ModraDoc006/r either at 30-20/200-100 mg or at 20-20/200-100 mg BIDW, plus 5 mg oral prednisone twice daily. |
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