Trial Outcomes & Findings for ModraDoc006/r vs Docetaxel IV in Metastatic Prostate Cancer (NCT NCT04028388)

Last Updated: 2024-04-17

Results Overview

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: * Progressive disease by RECIST v1.1. for soft tissue disease * Or the appearance of 2 or more new bone lesions on bone scan (PCWG3)

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

135 participants

Primary outcome timeframe

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.

Results posted on

2024-04-17

Participant Flow

The number of enrollment is not equal to the number of patients started, because 32 patients did not meet the inclusion criteria.

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	51	52
Overall Study COMPLETED	46	46
Overall Study NOT COMPLETED	5	6

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
Overall Study Evaluations missing	3	6
Overall Study Not started	2	0

Baseline Characteristics

ModraDoc006/r vs Docetaxel IV in Metastatic Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Docetaxel IV n=46 Participants Patients received docetaxel at 75 mg/m2 i.v. Q3W, with dexamethasone premedication, plus 5 mg oral prednisone twice daily.	ModraDoc006/r n=46 Participants 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.	Total n=92 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	11 Participants n=5 Participants	11 Participants n=7 Participants	22 Participants n=5 Participants
Age, Categorical >=65 years	35 Participants n=5 Participants	35 Participants n=7 Participants	70 Participants n=5 Participants
Age, Continuous	67.8 years STANDARD_DEVIATION 6.6 • n=5 Participants	67.0 years STANDARD_DEVIATION 6.9 • n=7 Participants	67.4 years STANDARD_DEVIATION 6.7 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	46 Participants n=5 Participants	46 Participants n=7 Participants	92 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	44 Participants n=5 Participants	45 Participants n=7 Participants	89 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) White	44 Participants n=5 Participants	44 Participants n=7 Participants	88 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Hungary	7 participants n=5 Participants	3 participants n=7 Participants	10 participants n=5 Participants
Region of Enrollment United States	11 participants n=5 Participants	13 participants n=7 Participants	24 participants n=5 Participants
Region of Enrollment Czechia	3 participants n=5 Participants	2 participants n=7 Participants	5 participants n=5 Participants
Region of Enrollment Poland	3 participants n=5 Participants	3 participants n=7 Participants	6 participants n=5 Participants
Region of Enrollment Germany	2 participants n=5 Participants	3 participants n=7 Participants	5 participants n=5 Participants
Region of Enrollment Russia	20 participants n=5 Participants	22 participants n=7 Participants	42 participants n=5 Participants
ECOG Performance Status at study entry Performance status 0	17 Participants n=5 Participants	29 Participants n=7 Participants	46 Participants n=5 Participants
ECOG Performance Status at study entry Performance status 1	28 Participants n=5 Participants	15 Participants n=7 Participants	43 Participants n=5 Participants
ECOG Performance Status at study entry Performance status 2	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Time since diagnosis of mCRPC	12.24 Months STANDARD_DEVIATION 14.92 • n=5 Participants	15.72 Months STANDARD_DEVIATION 29.48 • n=7 Participants	13.98 Months STANDARD_DEVIATION 23.30 • n=5 Participants
RECIST measurable disease at study entry Yes	33 Participants n=5 Participants	36 Participants n=7 Participants	69 Participants n=5 Participants
RECIST measurable disease at study entry No	13 Participants n=5 Participants	10 Participants n=7 Participants	23 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Population: 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.

Outcome measures

Outcome measures
Measure	Docetaxel IV n=13 Participants Patients received docetaxel at 75 mg/m2 i.v. Q3W, with dexamethasone premedication, plus 5 mg oral prednisone twice daily.	ModraDoc006/r n=13 Participants 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.
Radiographic Progression Free Survival (rPFS)	11.1 Months Interval 7.9 to 13.1	9.5 Months Interval 6.8 to The upper limit of the 95% confidence interval was not calculable due to an insufficient number of participants with events.

SECONDARY outcome

Timeframe: Evaluation of all adverse events during the complete study treatment until 28 days after the last intake, an average of 1 year.

Population: 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.

The hematological and non-hematological safety profile of ModraDoc006/r will be assessed by clinical and laboratory evaluations according to CTCAE v5.0.

Outcome measures

Outcome measures
Measure	Docetaxel IV n=49 Participants Patients received docetaxel at 75 mg/m2 i.v. Q3W, with dexamethasone premedication, plus 5 mg oral prednisone twice daily.	ModraDoc006/r n=52 Participants 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.
Adverse Event Profile (Safety) Any adverse event	48 Participants	50 Participants
Adverse Event Profile (Safety) Any treatment-related adverse event	43 Participants	43 Participants
Adverse Event Profile (Safety) Adverse events leading to treatment discontinuation	12 Participants	13 Participants
Adverse Event Profile (Safety) Serious adverse events	16 Participants	13 Participants
Adverse Event Profile (Safety) Treatment-related serious adverse events	8 Participants	6 Participants
Adverse Event Profile (Safety) Serious adverse events leading to death	3 Participants	3 Participants
Adverse Event Profile (Safety) Treatment-related serious adverse events leading to death	0 Participants	2 Participants
Adverse Event Profile (Safety) Serious adverse events leading to treatment discontinuation	5 Participants	5 Participants

SECONDARY outcome

Timeframe: From baseline during the complete study treatment, including follow-up visit 28 days after the last treatment, an average of 1 year.

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Docetaxel IV n=31 Participants Patients received docetaxel at 75 mg/m2 i.v. Q3W, with dexamethasone premedication, plus 5 mg oral prednisone twice daily.	ModraDoc006/r n=34 Participants 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.
Overall Response Rate (ORR)	38.7 Percentage of participants analyzed Interval 21.8 to 57.8	44.1 Percentage of participants analyzed Interval 27.2 to 62.1

SECONDARY outcome

Timeframe: From baseline through study completion, an average of 1 year

Population: Population evaluable for radiological response (ERR).

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.

Outcome measures

Outcome measures
Measure	Docetaxel IV n=31 Participants Patients received docetaxel at 75 mg/m2 i.v. Q3W, with dexamethasone premedication, plus 5 mg oral prednisone twice daily.	ModraDoc006/r n=34 Participants 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.
Disease Control Rate (DCR)	96.8 Percentage of participants analyzed Interval 83.3 to 99.9	88.2 Percentage of participants analyzed Interval 72.5 to 96.7

SECONDARY outcome

Timeframe: From baseline through study completion, an average of 1 year

Population: Population evaluable for radiological response (ERR).

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.

Outcome measures

Outcome measures
Measure	Docetaxel IV n=31 Participants Patients received docetaxel at 75 mg/m2 i.v. Q3W, with dexamethasone premedication, plus 5 mg oral prednisone twice daily.	ModraDoc006/r n=34 Participants 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.
Duration of Response (DOR)	NA Months Interval 1.5 to The median months in Docetaxel IV was not estimable due to an insufficient number of participants with events. The upper limit of the 95% confidence interval was not calculable due to an insufficient number of participants with events.	4.9 Months Interval 1.6 to The upper limit of the 95% confidence interval was not calculable due to an insufficient number of participants with events.

SECONDARY outcome

Timeframe: Time from the date of randomization to the date of the first radiologic progression, an average of 1 year.

Population: Full Analysis Set

Time to Progression is defined as the time from the date of randomization to the date of the first radiologic progression per PCWG3 criteria.

Outcome measures

Outcome measures
Measure	Docetaxel IV n=46 Participants Patients received docetaxel at 75 mg/m2 i.v. Q3W, with dexamethasone premedication, plus 5 mg oral prednisone twice daily.	ModraDoc006/r n=46 Participants 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.
Time to Progression (TTP)	11.1 Months Interval 8.4 to The upper limit of the 95% confidence interval was not calculable due to an insufficient number of participants with events.	NA Months Interval 6.8 to The median months in ModraDoc006/r was not estimable due to an insufficient number of participants with events. The upper limit of the 95% confidence interval was not calculable due to an insufficient number of participants with events.

SECONDARY outcome

Timeframe: From baseline through study completion, an average of 1 year

Population: Full Analysis Set

PSA decline of \>50% from baseline with confirmatory read ≥3 weeks later, based on the Prostate Cancer Working Group 3 (PCWG3) criteria recommendations.

Outcome measures

Outcome measures
Measure	Docetaxel IV n=46 Participants Patients received docetaxel at 75 mg/m2 i.v. Q3W, with dexamethasone premedication, plus 5 mg oral prednisone twice daily.	ModraDoc006/r n=46 Participants 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.
PSA Response Rate	26 Participants	23 Participants

SECONDARY outcome

Timeframe: 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.

Population: Full Analysis Set

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: * If a patient presented first a decline from baseline, progression was defined as the first PSA increase that was ≥25% and ≥2 ng/mL above the nadir, and which was confirmed by a consecutive second value ≥3 weeks later that fulfilled the same criteria (i.e., a confirmed rising trend) * If a patient did not present a decline from baseline, progression was defined as the first PSA increase that was ≥25% and ≥2 ng/mL increased from baseline beyond 12 weeks.

Outcome measures

Outcome measures
Measure	Docetaxel IV n=46 Participants Patients received docetaxel at 75 mg/m2 i.v. Q3W, with dexamethasone premedication, plus 5 mg oral prednisone twice daily.	ModraDoc006/r n=46 Participants 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.
PSA-PFS	7.7 Months Interval 4.9 to 11.3	4.9 Months Interval 3.5 to 7.6

SECONDARY outcome

Timeframe: From baseline through study completion, an average of 1 year

Population: Full Analysis Set

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: * If a patient presented first a decline from baseline, progression was defined as the first PSA increase that was ≥25% and ≥2 ng/mL above the nadir, and which was confirmed by a consecutive second value ≥3 weeks later that fulfilled the same criteria (i.e., a confirmed rising trend) * If a patient did not present a decline from baseline, progression was defined as the first PSA increase that was ≥25% and ≥2 ng/mL increased from baseline beyond 12 weeks.

Outcome measures

Outcome measures
Measure	Docetaxel IV n=46 Participants Patients received docetaxel at 75 mg/m2 i.v. Q3W, with dexamethasone premedication, plus 5 mg oral prednisone twice daily.	ModraDoc006/r n=46 Participants 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.
Time to PSA Progression	7.7 Months Interval 4.9 to 11.3	4.9 Months Interval 3.5 to 7.6

SECONDARY outcome

Timeframe: From baseline through study completion, an average of 1 year

Population: Full Analysis Set

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.

Outcome measures

Outcome measures
Measure	Docetaxel IV n=46 Participants Patients received docetaxel at 75 mg/m2 i.v. Q3W, with dexamethasone premedication, plus 5 mg oral prednisone twice daily.	ModraDoc006/r n=46 Participants 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.
Number of Participants Who Experienced a First Skeletal-Related Event Censored	44 participants	46 participants
Number of Participants Who Experienced a First Skeletal-Related Event Event	2 participants	0 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline through to end of Cycle 10 (each cycle was 21 days)

Population: Full Analysis Set

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.

Outcome measures

Outcome measures
Measure	Docetaxel IV n=46 Participants Patients received docetaxel at 75 mg/m2 i.v. Q3W, with dexamethasone premedication, plus 5 mg oral prednisone twice daily.	ModraDoc006/r n=46 Participants 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.
Overall Health-Related Quality of Life Response	15 Participants	15 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Improvement assessed at any timepoint from baseline through to End of Cycle 10 (each cycle was 21 days)

Population: Full Analysis Set

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)

Outcome measures

Outcome measures
Measure	Docetaxel IV n=46 Participants Patients received docetaxel at 75 mg/m2 i.v. Q3W, with dexamethasone premedication, plus 5 mg oral prednisone twice daily.	ModraDoc006/r n=46 Participants 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.
Summary of Improvement by Individual Health- Related Quality of Life Domains ≥3 for FACT-G physical well-being	9 Participants	13 Participants
Summary of Improvement by Individual Health- Related Quality of Life Domains ≥3 for FACT-G social or family well being	16 Participants	16 Participants
Summary of Improvement by Individual Health- Related Quality of Life Domains ≥3 for FACT-G emotional well-being	23 Participants	18 Participants
Summary of Improvement by Individual Health- Related Quality of Life Domains ≥3 for FACT-G functional well-being	18 Participants	21 Participants
Summary of Improvement by Individual Health- Related Quality of Life Domains ≥3 for FACT-P	21 Participants	23 Participants
Summary of Improvement by Individual Health- Related Quality of Life Domains ≥3 for FACT-T specific items	19 Participants	23 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Assessed from baseline to End of Cycle 10 (each cycle was 21 days)

Population: Full Analysis Set

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.

Outcome measures

Outcome measures
Measure	Docetaxel IV n=46 Participants Patients received docetaxel at 75 mg/m2 i.v. Q3W, with dexamethasone premedication, plus 5 mg oral prednisone twice daily.	ModraDoc006/r n=46 Participants 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.
Overall Health-Related Utility Mobility	0.4 Change of score on a scale Standard Deviation 1.1	0.4 Change of score on a scale Standard Deviation 1.0
Overall Health-Related Utility Self-care	0.3 Change of score on a scale Standard Deviation 1.1	0.0 Change of score on a scale Standard Deviation 0.7
Overall Health-Related Utility Usual activities	0.5 Change of score on a scale Standard Deviation 1.3	0.1 Change of score on a scale Standard Deviation 0.9
Overall Health-Related Utility Pain/discomfort	0.4 Change of score on a scale Standard Deviation 1.3	0.1 Change of score on a scale Standard Deviation 0.7
Overall Health-Related Utility Anxiety/depression	0.0 Change of score on a scale Standard Deviation 0.8	0.0 Change of score on a scale Standard Deviation 0.8
Overall Health-Related Utility Health state	-9.4 Change of score on a scale Standard Deviation 22.2	-5.9 Change of score on a scale Standard Deviation 20.5

OTHER_PRE_SPECIFIED outcome

Timeframe: Score assessed at end of treatment visit (up to 2 years).

Population: Safety population (SAF)

Eastern Cooperative Oncology Group (ECOG) scores at the time of end on treatment visit are presented. 0 = Normal activity 1. = Symptoms, but nearly ambulatory 2. = Symptomatic, but in bed \<50% of the day 3. = Needs to be in bed \>50% of the day, but not bedridden 4. = Unable to get out of bed 5. = Dead

Outcome measures

Outcome measures
Measure	Docetaxel IV n=49 Participants Patients received docetaxel at 75 mg/m2 i.v. Q3W, with dexamethasone premedication, plus 5 mg oral prednisone twice daily.	ModraDoc006/r n=52 Participants 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.
World Health Organization Performance Status (Eastern Cooperative Oncology Group) at End of Treatment ECOG Score 0	10 Participants	17 Participants
World Health Organization Performance Status (Eastern Cooperative Oncology Group) at End of Treatment ECOG Score 1	16 Participants	13 Participants
World Health Organization Performance Status (Eastern Cooperative Oncology Group) at End of Treatment ECOG Score 2	4 Participants	3 Participants
World Health Organization Performance Status (Eastern Cooperative Oncology Group) at End of Treatment ECOG Score 3	0 Participants	1 Participants
World Health Organization Performance Status (Eastern Cooperative Oncology Group) at End of Treatment ECOG Score 4	0 Participants	0 Participants
World Health Organization Performance Status (Eastern Cooperative Oncology Group) at End of Treatment ECOG Score 5	2 Participants	1 Participants

Adverse Events

Docetaxel IV

Serious events: 16 serious events

Other events: 32 other events

Deaths: 4 deaths

ModraDoc006/r

Serious events: 13 serious events

Other events: 37 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Additional Information

M. Keessen

Modra Pharmaceuticals

Phone: +31202050188

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Docetaxel IV n=49 participants at risk Patients received docetaxel at 75 mg/m2 i.v. Q3W, with dexamethasone premedication, plus 5 mg oral prednisone twice daily.	ModraDoc006/r n=52 participants at risk 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.
Vascular disorders Orthostatic hypotension	2.0% 1/49 • Number of events 1 • 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.	0.00% 0/52 • 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	2.0% 1/49 • Number of events 1 • 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.	0.00% 0/52 • 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.
General disorders Asthenia	0.00% 0/49 • 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.	1.9% 1/52 • Number of events 1 • 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.
General disorders Death	2.0% 1/49 • Number of events 1 • 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.	0.00% 0/52 • 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.
General disorders Fatigue	0.00% 0/49 • 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.	1.9% 1/52 • Number of events 1 • 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.
General disorders Pyrexia	2.0% 1/49 • Number of events 1 • 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.	0.00% 0/52 • 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.
Blood and lymphatic system disorders Neutropenia	2.0% 1/49 • Number of events 1 • 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.	1.9% 1/52 • Number of events 1 • 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.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/49 • 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.	1.9% 1/52 • Number of events 1 • 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.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	2.0% 1/49 • Number of events 1 • 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.	0.00% 0/52 • 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.
Nervous system disorders Aphasia	0.00% 0/49 • 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.	1.9% 1/52 • Number of events 1 • 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.
Nervous system disorders Hemiparesis	0.00% 0/49 • 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.	1.9% 1/52 • Number of events 1 • 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.
Nervous system disorders Seizure	0.00% 0/49 • 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.	1.9% 1/52 • Number of events 1 • 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.
Gastrointestinal disorders Vomiting	0.00% 0/49 • 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.	1.9% 1/52 • Number of events 1 • 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.
Gastrointestinal disorders Dental caries	2.0% 1/49 • Number of events 1 • 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.	0.00% 0/52 • 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.
Gastrointestinal disorders Diarrhoea	0.00% 0/49 • 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.	1.9% 1/52 • Number of events 1 • 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.
Gastrointestinal disorders Duodenal ulcer	0.00% 0/49 • 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.	1.9% 1/52 • Number of events 1 • 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.
Gastrointestinal disorders Peptic ulcer	2.0% 1/49 • Number of events 1 • 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.	0.00% 0/52 • 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.
Gastrointestinal disorders Stomatitis	0.00% 0/49 • 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.	1.9% 1/52 • Number of events 1 • 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.
Hepatobiliary disorders Acute hepatic failure	0.00% 0/49 • 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.	1.9% 1/52 • Number of events 1 • 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.
Renal and urinary disorders Hydronephrosis	0.00% 0/49 • 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.	1.9% 1/52 • Number of events 1 • 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.
Renal and urinary disorders Urinary retention	0.00% 0/49 • 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.	1.9% 1/52 • Number of events 1 • 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.
Musculoskeletal and connective tissue disorders Bone pain	2.0% 1/49 • Number of events 1 • 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.	0.00% 0/52 • 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.
Musculoskeletal and connective tissue disorders Pathological fracture	0.00% 0/49 • 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.	1.9% 1/52 • Number of events 1 • 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.
Metabolism and nutrition disorders Dehydration	2.0% 1/49 • Number of events 1 • 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.	0.00% 0/52 • 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.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/49 • 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.	1.9% 1/52 • Number of events 1 • 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.
Infections and infestations Corona virus infection	6.1% 3/49 • Number of events 3 • 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.	1.9% 1/52 • Number of events 1 • 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.
Infections and infestations Bronchitis	2.0% 1/49 • Number of events 1 • 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.	0.00% 0/52 • 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.
Infections and infestations Cellulitis	2.0% 1/49 • Number of events 1 • 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.	0.00% 0/52 • 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.
Infections and infestations Erysipelas	2.0% 1/49 • Number of events 1 • 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.	0.00% 0/52 • 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.
Infections and infestations Escherichia urinary tract infection	2.0% 1/49 • Number of events 1 • 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.	0.00% 0/52 • 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.
Infections and infestations Osteomyelitis	2.0% 1/49 • Number of events 1 • 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.	0.00% 0/52 • 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.
Infections and infestations Pneumonia	0.00% 0/49 • 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.	1.9% 1/52 • Number of events 1 • 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.
Infections and infestations Pneumonia viral (Covid-19)	2.0% 1/49 • Number of events 1 • 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.	0.00% 0/52 • 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.
Infections and infestations Sepsis	2.0% 1/49 • Number of events 1 • 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.	0.00% 0/52 • 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.