TAXYNERGY: Early Switch From First-Line Docetaxel/Prednisone to Cabazitaxel/Prednisone and the Opposite Sequence, Exploring Molecular Markers in Men With Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Study Details
Study Description
Brief Summary
Docetaxel and cabazitaxel are cancer chemotherapy agents of the taxane drug class. The purpose of this study is to explore the benefit, for treatment of metastatic castration-resistant prostate cancer (mCRPC), of a regimen in which participants begin treatment with either of these two taxane drugs (docetaxel or cabazitaxel, in combination with prednisone) and are switched to the other taxane drug if prostate-specific antigen (PSA) value does not decrease ≥30% after 4 cycles. As defined in study protocol amendment 3, efficacy results are summarized for all participants combined, irrespective of which agent (docetaxel or cabazitaxel) was administered initially, rather than separately for the two groups based on taxane administered initially. One of the primary outcome measures is percentage of participants with a ≥50% sustained decrease from baseline in PSA at any time during the trial. By providing an opportunity for patients to switch taxane based on early PSA response, there may be a difference in result for this measure versus result in a study where it was not possible to switch. The other primary outcome measures are change from baseline in circulating tumor cells (CTCs) biomarkers percent androgen receptor nuclear localization (%ARNL) and microtubule bundling (MTB).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
-
Participants were treated until progressive disease, unacceptable toxicity, death, or participant's refusal of further study treatment. All participants were followed until death or the study cut-off date, whichever came first.
-
Study cut-off was 1 month after the last participant last treatment.
-
Participants alive at the cut-off date were not followed for overall survival.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Docetaxel + Prednisone (Treatment A) Docetaxel 75 mg/m^2 intravenous (IV) infusion on Day 1 of Cycle 1 and every 3 weeks (q3w) thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily. Participants with <30% PSA reduction from baseline at the end of Cycle 4 switched to Cabazitaxel 25mg/m^2 IV infusion on Day 1 of Cycle 5 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily until disease progression (DP), death, unacceptable toxicity or participant's refusal of further study treatment. Participants with ≥30% PSA reduction from baseline at the end of Cycle 4, continued on the same treatment which they received before switching until DP, death, unacceptable toxicity or participant's refusal of further study treatment. |
Drug: DOCETAXEL (XRP6976)
Pharmaceutical form: Concentrate for solution for infusion Route of administration: Intravenous
Other Names:
Drug: Prednisone
Pharmaceutical form: Tablet Route of administration: Oral
|
| Experimental: Cabazitaxel + Prednisone (Treatment B) Cabazitaxel 25 mg/m^2 IV infusion on Day 1 of Cycle 1 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily. Participants with <30% PSA reduction from baseline at the end of Cycle 4 switched to Docetaxel 75mg/m^2 IV infusion on Day 1 of Cycle 5 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, death, unacceptable toxicity or participant's refusal of further study treatment. Participants with ≥30% PSA reduction from baseline at the end of Cycle 4, continued on the same treatment which they received before switching until DP, death, unacceptable toxicity or participant's refusal of further study treatment. |
Drug: CABAZITAXEL (XRP6258)
Pharmaceutical form: Concentrate and solvent for solution for infusion Route of administration: Intravenous
Other Names:
Drug: Prednisone
Pharmaceutical form: Tablet Route of administration: Oral
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants With PSA Response [Baseline, Pre-dose every 3 weeks, 30 days after last treatment administration (End of treatment [EOT]), every 3 months (for 1 year) then every 6 months until PSA progression or study cut-off, whichever was earlier (Maximum duration: 60 weeks)]
PSA response was defined as ≥50% decrease in PSA levels in both treatment arms from baseline, during the whole treatment, before treatment switch and after treatment switch. PSA progression was defined as decline of PSA from baseline (an increase of ≥25% [at least 2ng/ml] over the nadir value, confirmed by a second PSA value at least 3 weeks apart) and no decline of PSA from baseline (an increase of ≥25% [at least 2ng/ml] over the baseline value after 12 weeks of treatment, confirmed by a second PSA value at least 3 weeks apart). Because the purpose of this study is to explore the benefit of a regimen in which participants are switched to a different taxane if PSA does not decrease ≥30% after 4 cycles, irrespective of which agent (docetaxel or cabazitaxel) is administered initially, the data for participants who began treatment with docetaxel and for those who began treatment with cabazitaxel were combined for the efficacy analyses.
- Drug-target Engagement in Circulating Tumor Cells (CTCs): Change From Baseline at Cycle 1 Day 8 in Percent Androgen Receptor Nuclear Localization (%ARNL) by Categories of PSA Decrease From Baseline (≥50%, Not ≥50%) After Cycle 4 [Baseline and Cycle 1 Day 8, Cycle 4]
Analysis of CTCs is a co-primary endpoint. Growth of prostate cancer cells is dependent on sustained androgen receptor (AR) nuclear signaling. Taxanes (e.g., docetaxel and cabazitaxel) may mediate some of their activity in prostate cancer by impairing AR trafficking along the microtubules from the tumor cell cytoplasm into the nucleus, as a result of taxane-induced microtubule bundling (MTB). Blood samples were collected at baseline and post-treatment to allow isolation of CTCs, which were evaluated for tumor cell biomarker measures %ARNL and MTB score. %ARNL was assessed by quantitative analysis of images of CTCs captured by geometrically enhanced differential immunocapture (GEDI). Reduction from baseline in %ARNL (percentage of total cellular AR that is located in the nucleus) may indicate inhibition of AR signaling. Change from baseline in %ARNL at Cycle 1 Day 8 is summarized by categories of participants with PSA decrease from baseline (≥50%, Not ≥50%) after Cycle 4.
- Drug-target Engagement in CTCs: Change From Baseline at Cycle 1 Day 8 in MTB by Categories of PSA Decrease From Baseline (≥30%, Not ≥30%) After Cycle 4 [Baseline and Cycle 1 Day 8, Cycle 4]
Analysis of CTCs is a co-primary endpoint. Growth of prostate cancer cells is dependent on sustained AR nuclear signaling. Taxanes (e.g., docetaxel and cabazitaxel) may mediate some of their activity in prostate cancer by impairing AR trafficking along the microtubules from the tumor cell cytoplasm into the nucleus, as a result of taxane-induced MTB. Blood samples were collected at baseline and post-treatment to allow isolation of CTCs, which were evaluated for tumor cell biomarker measures %ARNL and MTB score. MTB in images of CTCs captured by GEDI was qualitatively assessed by three independent operators for increase compared with baseline on a scale of 0 to 3 from no to most MTB increase. Increase from baseline in MTB may indicate inhibition of AR signaling. Change from baseline in MTB at Cycle 1 Day 8 is summarized by categories of participants with PSA decrease from baseline (≥30%, Not ≥30%) after Cycle 4.
Secondary Outcome Measures
- Progression Free Survival (PFS) [From Baseline until DP or death due to any cause or study cut off, whichever was earlier (Maximum duration: 60 weeks)]
PFS was defined as the time interval between the date of random allocation of the treatment and the date of first documentation of any of the following: radiographic tumor progression (using Modified Response Evaluation Criteria in Solid Tumors [RECIST1.1] before any switch and during the study), clinical progression (including skeletal-related events, increasing pain requiring escalation of narcotic analgesics, urinary obstruction), PSA progression or death from any cause. Analysis was performed by Kaplan Meier method.
- PSA Progression Free Survival [From Baseline until DP or death due to any cause or study cut off date, whichever was earlier (Maximum duration: 60 weeks)]
PSA progression-free survival before any switch and PSA progression free survival during the study was defined as the time interval between the date of Day 1 of Cycle 1 to the date of either first PSA progression or death due to any cause whichever came first. PSA progression was defined as decline of PSA from baseline (an increase of ≥25% [at least 2ng/mL] over the nadir value, confirmed by a second PSA value at least 3 weeks apart) and no decline of PSA from baseline (an increase of ≥25% [at least 2ng/mL] over the baseline value after 12 weeks of treatment, confirmed by a second PSA value at least 3 weeks apart).
- Percentage of Participants With Objective Response [From baseline until DP or study cut off, whichever was earlier (Maximum duration: 60 weeks)]
- Radiographic Progression-free Survival (rPFS) [From baseline, every 12 weeks until radiological tumor progression or study cut-off, whichever was earlier (Maximum duration: 60 weeks)]
- Clinical Progression-free Survival (cPFS) [Baseline, Pre-dose every 3 weeks, EOT, every 3 months (for 1 year) until first SRE occurrence or death or study cut-off, whichever was earlier (Maximum duration: 60 weeks)]
cPFS was assessed before switch and during the study including skeletal-related events (SRE), increasing pain requiring escalation of narcotic analgesics, urinary obstruction, etc. SRE included pathological fractures and/or spinal cord compression, need for bone irradiation (including radioisotopes or bone surgery), change of antineoplastic therapy (including introduction of bisphosphonates or denosumab in the face of increase in pain) to treat bone pain. Pain was assessed using present pain intensity (PPI) scale (0=no pain, up to 5=excruciating pain) and analgesics used for cancer pain (1 point for non-narcotic medications and 4 points for narcotic medications).
- Overall Survival [From baseline until death due to any cause or study cut-off, whichever was earlier (Maximum duration: 60 weeks)]
Overall survival before switch and overall survival during the study was defined as the time interval from the date of random allocation to the date of death due to any cause until study cut-off date.
- Percentage of Participants With ≥30% and ≥50% Reduction in PSA Response [From baseline until DP or study cut-off, whichever was earlier (Maximum duration: 60 weeks)]
Participants with ≥30% and ≥50% reduction in PSA response from base line were evaluated in participants who were previously treated with a high potency androgen receptor (AR)-targeted agent (AR signaling inhibitor or cytochrome P450 17 alphahydroxylase/17,20lyase [CYP 17] inhibitor).
Eligibility Criteria
Criteria
Inclusion criteria :
-
Histologically- or cytologically-confirmed prostate adenocarcinoma with documented distant metastases (M1 disease).
-
Progressive disease while receiving hormonal therapy or after surgical castration.
-
Effective castration (serum testosterone levels ≤50 ng/dL) by orchiectomy and/or luteinizing hormone releasing hormone agonists or antagonist with or without anti-androgens.
Exclusion criteria:
-
Prior chemotherapy for prostate cancer, except estramustine and adjuvant/neoadjuvant treatment completed >3 years ago. Prior treatment with sipuleucel-T immunotherapy was allowed at the condition participant did not receive prior chemotherapy.
-
Less than 28 days elapsed from prior treatment with estramustine, radiotherapy or surgery to the time of random allocation.
-
Prior beta isotope therapy, whole pelvic radiotherapy, or radiotherapy to >30% of bone marrow.
-
Adverse events (excluding alopecia and those listed in the specific exclusion criteria) from any prior anticancer therapy of grade >1(National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v4.03) at the time of random allocation.
-
Less than 18 years of age.
-
Eastern Cooperative Oncology Group (ECOG) performance status >2.
-
History of brain metastases, uncontrolled spinal cord compression, or carcinomatous meningitis or new evidence of brain or leptomeningeal disease.
-
Prior malignancy. Adequately treated basal cell or squamous cell skin or superficial (pTis, pTa and pT1) bladder cancer were allowed, as well as any other cancer for which chemotherapy had been completed ≥3 years ago and from which the participant had been disease-free for ≥3 years.
-
Participation in another clinical trial and any concurrent treatment with any investigational drug within 30 days prior to random allocation.
-
Any of the following within 6 months prior to study enrollment: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart Association (NYHA) class III or IV congestive heart failure, stroke or transient ischemic attack.
-
Any of the following within 3 months prior to random allocation: treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism, or other uncontrolled thromboembolic event.
-
Acquired immunodeficiency syndrome (AIDS)-related illnesses or known HIV disease requiring antiretroviral treatment.
-
Any severe acute or chronic medical condition which could impair the ability of the participant to participate in to the study or interfere with interpretation of study results, or participant unable to comply with the study procedures.
-
Concomitant treatment with biphosphonates or denosumab except if the dose had been stable for 4 weeks prior to enrollment.
-
Absence of signed and dated Institutional Review Board (IRB)-approved participant informed consent prior to enrollment into the study.
-
Participants with reproductive potential who did not agree to use an accepted and effective method of contraception during the study treatment period. The definition of "effective method of contraception" was based on the investigator's judgment.
-
History of hypersensitivity to docetaxel or polysorbate 80.
-
Inadequate organ and bone marrow function.
-
Contraindications to the use of corticosteroid treatment.
-
Symptomatic peripheral neuropathy grade >2 (NCI CTCAE v.4.03).
-
Treatment with strong inhibitors or strong inducers of cytochrome P450 3A4/5 (a two-week wash-out period was necessary for participants who were already on these treatments).
The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Investigational Site Number 840003 | Birmingham | Alabama | United States | 35294-3300 |
| 2 | Investigational Site Number 840102 | Washington, D.C. | District of Columbia | United States | 20016-2695 |
| 3 | Investigational Site Number 840005 | Indianapolis | Indiana | United States | 46202 |
| 4 | Investigational Site Number 840025 | Metairie | Louisiana | United States | 70006 |
| 5 | Investigational Site Number 840002 | Baltimore | Maryland | United States | 21230 |
| 6 | Investigational Site Number 840007 | Bethesda | Maryland | United States | 20817 |
| 7 | Investigational Site Number 840017 | Rockville | Maryland | United States | 20850 |
| 8 | Investigational Site Number 840010 | Cherry Hill | New Jersey | United States | 08003 |
| 9 | Investigational Site Number 840015 | East Orange | New Jersey | United States | 07018 |
| 10 | Investigational Site Number 840001 | New York | New York | United States | 10021 |
| 11 | Investigational Site Number 840013 | New York | New York | United States | 10029-6574 |
| 12 | Investigational Site Number 840009 | Charleston | South Carolina | United States | 29414 |
| 13 | Investigational Site Number 840012 | Seattle | Washington | United States | 98109 |
| 14 | Investigational Site Number 840004 | Madison | Wisconsin | United States | 53705 |
| 15 | Investigational Site Number 124001 | Edmonton | Alberta | Canada | T6G 1Z2 |
| 16 | Investigational Site Number 124004 | Montreal | Quebec | Canada | H2L 4M1 |
| 17 | Investigational Site Number 124002 | Montreal | Quebec | Canada | H2W1S6 |
| 18 | Investigational Site Number 124006 | Québec | Quebec | Canada | G1R 2J6 |
| 19 | Investigational Site Number 124005 | Sherbrooke | Quebec | Canada | J1H 5N4 |
Sponsors and Collaborators
- Sanofi
Investigators
- Study Director: Clinical Sciences & Operations, Sanofi
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CABAZL06056
- U1111-1130-9893
Study Results
Participant Flow
| Recruitment Details | The study was conducted at 19 centers in Canada and United States. A total of 81 participants were screened between 20 March 2013 and 29 May 2014, of which, 63 participants were randomized and 61 were treated. A total of 18 participants were screen failure mainly due to exclusion criteria met and inclusion criteria not met. |
|---|---|
| Pre-assignment Detail | Participants were randomized by Interactive Voice Response System (IVRS) in 2:1 ratio (Treatment A : Treatment B) to receive either Treatment A (Docetaxel + Prednisone) or Treatment B (Cabazitaxel + Prednisone). |
| Arm/Group Title | Docetaxel + Prednisone (Treatment A) | Cabazitaxel + Prednisone (Treatment B) |
|---|---|---|
| Arm/Group Description | Docetaxel 75 mg/m^2 intravenous (IV) infusion on Day 1 of Cycle 1 and every 3 weeks (q3w) thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily. Participants with <30% prostate-specific antigen (PSA) reduction from baseline at the end of Cycle 4 switched to Cabazitaxel 25mg/m^2 IV infusion on Day 1 of Cycle 5 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily until disease progression (DP), death, unacceptable toxicity or participant's refusal of further study treatment. Participants with ≥30% PSA reduction from baseline at the end of Cycle 4, continued on the same treatment which they received before switching until DP, death, unacceptable toxicity or participant's refusal of further study treatment. | Cabazitaxel 25 mg/m^2 IV infusion on Day 1 of Cycle 1 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily. Participants with <30% PSA reduction from baseline at the end of Cycle 4 switched to Docetaxel 75mg/m^2 IV infusion on Day 1 of Cycle 5 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, death, unacceptable toxicity or participant's refusal of further study treatment. Participants with ≥30% PSA reduction from baseline at the end of Cycle 4, continued on the same treatment which they received before switching until DP, death, unacceptable toxicity or participant's refusal of further study treatment. |
| Period Title: Overall Study | ||
| STARTED | 41 | 22 |
| Treated | 39 | 22 |
| Treated up to End of Cycle 4 | 32 | 16 |
| Treated From Cycle 5 | 23 | 25 |
| COMPLETED | 29 | 17 |
| NOT COMPLETED | 12 | 5 |
Baseline Characteristics
| Arm/Group Title | Docetaxel + Prednisone (Treatment A) | Cabazitaxel + Prednisone (Treatment B) | Total |
|---|---|---|---|
| Arm/Group Description | Docetaxel 75 mg/m^2 IV infusion on Day 1 of Cycle 1 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily. Participants with <30% PSA reduction from baseline at the end of Cycle 4 switched to Cabazitaxel 25mg/m^2 IV infusion on Day 1 of Cycle 5 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, death, unacceptable toxicity or participant's refusal of further study treatment. Participants with ≥30% PSA reduction from baseline at the end of Cycle 4, continued on the same treatment which they received before switching until DP, death, unacceptable toxicity or participant's refusal of further study treatment. | Cabazitaxel 25 mg/m^2 IV infusion on Day 1 of Cycle 1 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily. Participants with <30% PSA reduction from baseline at the end of Cycle 4 switched to Docetaxel 75mg/m^2 IV infusion on Day 1 of Cycle 5 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, death, unacceptable toxicity or participant's refusal of further study treatment. Participants with ≥30% PSA reduction from baseline at the end of Cycle 4, continued on the same treatment which they received before switching until DP, death, unacceptable toxicity or participant's refusal of further study treatment. | Total of all reporting groups |
| Overall Participants | 41 | 22 | 63 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
69.9
(7.8)
|
69.2
(9.5)
|
69.7
(8.4)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
0
0%
|
0
0%
|
0
0%
|
| Male |
41
100%
|
22
100%
|
63
100%
|
Outcome Measures
| Title | Percentage of Participants With PSA Response |
|---|---|
| Description | PSA response was defined as ≥50% decrease in PSA levels in both treatment arms from baseline, during the whole treatment, before treatment switch and after treatment switch. PSA progression was defined as decline of PSA from baseline (an increase of ≥25% [at least 2ng/ml] over the nadir value, confirmed by a second PSA value at least 3 weeks apart) and no decline of PSA from baseline (an increase of ≥25% [at least 2ng/ml] over the baseline value after 12 weeks of treatment, confirmed by a second PSA value at least 3 weeks apart). Because the purpose of this study is to explore the benefit of a regimen in which participants are switched to a different taxane if PSA does not decrease ≥30% after 4 cycles, irrespective of which agent (docetaxel or cabazitaxel) is administered initially, the data for participants who began treatment with docetaxel and for those who began treatment with cabazitaxel were combined for the efficacy analyses. |
| Time Frame | Baseline, Pre-dose every 3 weeks, 30 days after last treatment administration (End of treatment [EOT]), every 3 months (for 1 year) then every 6 months until PSA progression or study cut-off, whichever was earlier (Maximum duration: 60 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on all randomized participants. |
| Arm/Group Title | Overall Population (Treatment A or Treatment B) |
|---|---|
| Arm/Group Description | Docetaxel 75 mg/m^2 or Cabazitaxel 25 mg/m^2 IV infusion on Day 1 of Cycle 1 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily. Participants with <30% PSA reduction from baseline at the end of Cycle 4, switched to Cabazitaxel 25 mg/m^2 IV or Docetaxel 75mg/m^2 IV infusion respectively on Day 1 of Cycle 5 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, death, unacceptable toxicity or participant's refusal of further study treatment. Participants with ≥30% PSA reduction from baseline at the end of Cycle 4, continued on the same treatment which they received before switching until DP, death, unacceptable toxicity or participant's refusal of further study treatment. |
| Measure Participants | 63 |
| PSA response before switch |
39.7
96.8%
|
| PSA response after switch |
15.9
38.8%
|
| Overall PSA response |
55.6
135.6%
|
| Title | Drug-target Engagement in Circulating Tumor Cells (CTCs): Change From Baseline at Cycle 1 Day 8 in Percent Androgen Receptor Nuclear Localization (%ARNL) by Categories of PSA Decrease From Baseline (≥50%, Not ≥50%) After Cycle 4 |
|---|---|
| Description | Analysis of CTCs is a co-primary endpoint. Growth of prostate cancer cells is dependent on sustained androgen receptor (AR) nuclear signaling. Taxanes (e.g., docetaxel and cabazitaxel) may mediate some of their activity in prostate cancer by impairing AR trafficking along the microtubules from the tumor cell cytoplasm into the nucleus, as a result of taxane-induced microtubule bundling (MTB). Blood samples were collected at baseline and post-treatment to allow isolation of CTCs, which were evaluated for tumor cell biomarker measures %ARNL and MTB score. %ARNL was assessed by quantitative analysis of images of CTCs captured by geometrically enhanced differential immunocapture (GEDI). Reduction from baseline in %ARNL (percentage of total cellular AR that is located in the nucleus) may indicate inhibition of AR signaling. Change from baseline in %ARNL at Cycle 1 Day 8 is summarized by categories of participants with PSA decrease from baseline (≥50%, Not ≥50%) after Cycle 4. |
| Time Frame | Baseline and Cycle 1 Day 8, Cycle 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants with evaluable CTCs at both baseline and Cycle 1 Day 8, and evaluable PSA result at both baseline and Cycle 4 |
| Arm/Group Title | Overall Population (Treatment A or Treatment B) |
|---|---|
| Arm/Group Description | Docetaxel 75 mg/m^2 or Cabazitaxel 25 mg/m^2 IV infusion on Day 1 of Cycle 1 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily. Participants with <30% PSA reduction from baseline at the end of Cycle 4, switched to Cabazitaxel 25 mg/m^2 IV or Docetaxel 75mg/m^2 IV infusion respectively on Day 1 of Cycle 5 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, death, unacceptable toxicity or participant's refusal of further study treatment. Participants with ≥30% PSA reduction from baseline at the end of Cycle 4, continued on the same treatment which they received before switching until DP, death, unacceptable toxicity or participant's refusal of further study treatment. |
| Measure Participants | 19 |
| PSA decreased ≥50% at Cycle 4 |
-17.58
(21.54)
|
| PSA not decreased ≥50% at Cycle 4 |
2.30
(11.16)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Overall Population (Treatment A or Treatment B) |
|---|---|---|
| Comments | %ARNL change from baseline at Cycle 1 Day 8 in participants with ≥50% decrease in PSA at Cycle 4 was compared with that of participants who did not have ≥50% decrease in PSA at Cycle 4 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.02 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Title | Progression Free Survival (PFS) |
|---|---|
| Description | PFS was defined as the time interval between the date of random allocation of the treatment and the date of first documentation of any of the following: radiographic tumor progression (using Modified Response Evaluation Criteria in Solid Tumors [RECIST1.1] before any switch and during the study), clinical progression (including skeletal-related events, increasing pain requiring escalation of narcotic analgesics, urinary obstruction), PSA progression or death from any cause. Analysis was performed by Kaplan Meier method. |
| Time Frame | From Baseline until DP or death due to any cause or study cut off, whichever was earlier (Maximum duration: 60 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on all randomized participants. |
| Arm/Group Title | Overall Population (Treatment A or Treatment B) |
|---|---|
| Arm/Group Description | Docetaxel 75 mg/m^2 or Cabazitaxel 25 mg/m^2 IV infusion on Day 1 of Cycle 1 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily. Participants with <30% PSA reduction from baseline at the end of Cycle 4, switched to Cabazitaxel 25 mg/m^2 IV or Docetaxel 75mg/m^2 IV infusion respectively on Day 1 of Cycle 5 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, death, unacceptable toxicity or participant's refusal of further study treatment. Participants with ≥30% PSA reduction from baseline at the end of Cycle 4, continued on the same treatment which they received before switching until DP, death, unacceptable toxicity or participant's refusal of further study treatment. |
| Measure Participants | 63 |
| Before switch |
4.1
|
| Whole treatment continuum |
9.1
|
| Title | PSA Progression Free Survival |
|---|---|
| Description | PSA progression-free survival before any switch and PSA progression free survival during the study was defined as the time interval between the date of Day 1 of Cycle 1 to the date of either first PSA progression or death due to any cause whichever came first. PSA progression was defined as decline of PSA from baseline (an increase of ≥25% [at least 2ng/mL] over the nadir value, confirmed by a second PSA value at least 3 weeks apart) and no decline of PSA from baseline (an increase of ≥25% [at least 2ng/mL] over the baseline value after 12 weeks of treatment, confirmed by a second PSA value at least 3 weeks apart). |
| Time Frame | From Baseline until DP or death due to any cause or study cut off date, whichever was earlier (Maximum duration: 60 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on all randomized population. |
| Arm/Group Title | Overall Population (Treatment A or Treatment B) |
|---|---|
| Arm/Group Description | Docetaxel 75 mg/m^2 or Cabazitaxel 25 mg/m^2 IV infusion on Day 1 of Cycle 1 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily. Participants with <30% PSA reduction from baseline at the end of Cycle 4, switched to Cabazitaxel 25 mg/m^2 IV or Docetaxel 75mg/m^2 IV infusion respectively on Day 1 of Cycle 5 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, death, unacceptable toxicity or participant's refusal of further study treatment. Participants with ≥30% PSA reduction from baseline at the end of Cycle 4, continued on the same treatment which they received before switching until DP, death, unacceptable toxicity or participant's refusal of further study treatment. |
| Measure Participants | 63 |
| Before switch |
NA
|
| whole treatment continuum |
12.4
|
| Title | Percentage of Participants With Objective Response |
|---|---|
| Description | |
| Time Frame | From baseline until DP or study cut off, whichever was earlier (Maximum duration: 60 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| No data was collected to determine the Objective Response, hence this outcome measure was not evaluated. |
| Arm/Group Title | Overall Population (Treatment A or Treatment B) |
|---|---|
| Arm/Group Description | Docetaxel 75 mg/m^2 or Cabazitaxel 25 mg/m^2 IV infusion on Day 1 of Cycle 1 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily. Participants with <30% PSA reduction from baseline at the end of Cycle 4, switched to Cabazitaxel 25 mg/m^2 IV or Docetaxel 75mg/m^2 IV infusion respectively on Day 1 of Cycle 5 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, death, unacceptable toxicity or participant's refusal of further study treatment. Participants with ≥30% PSA reduction from baseline at the end of Cycle 4, continued on the same treatment which they received before switching until DP, death, unacceptable toxicity or participant's refusal of further study treatment. |
| Measure Participants | 0 |
| Title | Radiographic Progression-free Survival (rPFS) |
|---|---|
| Description | |
| Time Frame | From baseline, every 12 weeks until radiological tumor progression or study cut-off, whichever was earlier (Maximum duration: 60 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on all randomized participants. |
| Arm/Group Title | Overall Population (Treatment A or Treatment B) |
|---|---|
| Arm/Group Description | Docetaxel 75 mg/m^2 or Cabazitaxel 25 mg/m^2 IV infusion on Day 1 of Cycle 1 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily. Participants with <30% PSA reduction from baseline at the end of Cycle 4, switched to Cabazitaxel 25 mg/m^2 IV or Docetaxel 75mg/m^2 IV infusion respectively on Day 1 of Cycle 5 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, death, unacceptable toxicity or participant's refusal of further study treatment. Participants with ≥30% PSA reduction from baseline at the end of Cycle 4, continued on the same treatment which they received before switching until DP, death, unacceptable toxicity or participant's refusal of further study treatment. |
| Measure Participants | 63 |
| Median (95% Confidence Interval) [months] |
NA
|
| Title | Clinical Progression-free Survival (cPFS) |
|---|---|
| Description | cPFS was assessed before switch and during the study including skeletal-related events (SRE), increasing pain requiring escalation of narcotic analgesics, urinary obstruction, etc. SRE included pathological fractures and/or spinal cord compression, need for bone irradiation (including radioisotopes or bone surgery), change of antineoplastic therapy (including introduction of bisphosphonates or denosumab in the face of increase in pain) to treat bone pain. Pain was assessed using present pain intensity (PPI) scale (0=no pain, up to 5=excruciating pain) and analgesics used for cancer pain (1 point for non-narcotic medications and 4 points for narcotic medications). |
| Time Frame | Baseline, Pre-dose every 3 weeks, EOT, every 3 months (for 1 year) until first SRE occurrence or death or study cut-off, whichever was earlier (Maximum duration: 60 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on all randomized participants. |
| Arm/Group Title | Overall Population (Treatment A or Treatment B) |
|---|---|
| Arm/Group Description | Docetaxel 75 mg/m^2 or Cabazitaxel 25 mg/m^2 IV infusion on Day 1 of Cycle 1 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily. Participants with <30% PSA reduction from baseline at the end of Cycle 4, switched to Cabazitaxel 25 mg/m^2 IV or Docetaxel 75mg/m^2 IV infusion respectively on Day 1 of Cycle 5 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, death, unacceptable toxicity or participant's refusal of further study treatment. Participants with ≥30% PSA reduction from baseline at the end of Cycle 4, continued on the same treatment which they received before switching until DP, death, unacceptable toxicity or participant's refusal of further study treatment. |
| Measure Participants | 63 |
| Before switch |
NA
|
| Whole treatment continuum |
NA
|
| Title | Overall Survival |
|---|---|
| Description | Overall survival before switch and overall survival during the study was defined as the time interval from the date of random allocation to the date of death due to any cause until study cut-off date. |
| Time Frame | From baseline until death due to any cause or study cut-off, whichever was earlier (Maximum duration: 60 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on all randomized participants. |
| Arm/Group Title | Overall Population (Treatment A or Treatment B) |
|---|---|
| Arm/Group Description | Docetaxel 75 mg/m^2 or Cabazitaxel 25 mg/m^2 IV infusion on Day 1 of Cycle 1 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily. Participants with <30% PSA reduction from baseline at the end of Cycle 4, switched to Cabazitaxel 25 mg/m^2 IV or Docetaxel 75mg/m^2 IV infusion respectively on Day 1 of Cycle 5 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, death, unacceptable toxicity or participant's refusal of further study treatment. Participants with ≥30% PSA reduction from baseline at the end of Cycle 4, continued on the same treatment which they received before switching until DP, death, unacceptable toxicity or participant's refusal of further study treatment. |
| Measure Participants | 63 |
| Before switch |
8.8
|
| whole treatment continuum |
NA
|
| Title | Percentage of Participants With ≥30% and ≥50% Reduction in PSA Response |
|---|---|
| Description | Participants with ≥30% and ≥50% reduction in PSA response from base line were evaluated in participants who were previously treated with a high potency androgen receptor (AR)-targeted agent (AR signaling inhibitor or cytochrome P450 17 alphahydroxylase/17,20lyase [CYP 17] inhibitor). |
| Time Frame | From baseline until DP or study cut-off, whichever was earlier (Maximum duration: 60 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on as-treated population that included all participants who received initial taxane treatment and had a post treatment assessment. Number of participants analyzed=participants treated/non-treated with AR-target agent and with PSA response assessment at specified time-points. |
| Arm/Group Title | Overall Population (AR-target Agent Treated) | Overall Population (Non AR-target Agent Treated) |
|---|---|---|
| Arm/Group Description | Participants having prior treatment experience with a high potency AR targeted agent (AR signaling inhibitor or CYP 17) before this study. | Participants not having prior treatment experience with a high potency AR targeted agent (AR signaling inhibitor or CYP 17 inhibitor) before this study. |
| Measure Participants | 25 | 35 |
| ≥30% reduction |
52.0
126.8%
|
74.3
337.7%
|
| ≥50% reduction |
44.0
107.3%
|
68.6
311.8%
|
| Title | Drug-target Engagement in CTCs: Change From Baseline at Cycle 1 Day 8 in MTB by Categories of PSA Decrease From Baseline (≥30%, Not ≥30%) After Cycle 4 |
|---|---|
| Description | Analysis of CTCs is a co-primary endpoint. Growth of prostate cancer cells is dependent on sustained AR nuclear signaling. Taxanes (e.g., docetaxel and cabazitaxel) may mediate some of their activity in prostate cancer by impairing AR trafficking along the microtubules from the tumor cell cytoplasm into the nucleus, as a result of taxane-induced MTB. Blood samples were collected at baseline and post-treatment to allow isolation of CTCs, which were evaluated for tumor cell biomarker measures %ARNL and MTB score. MTB in images of CTCs captured by GEDI was qualitatively assessed by three independent operators for increase compared with baseline on a scale of 0 to 3 from no to most MTB increase. Increase from baseline in MTB may indicate inhibition of AR signaling. Change from baseline in MTB at Cycle 1 Day 8 is summarized by categories of participants with PSA decrease from baseline (≥30%, Not ≥30%) after Cycle 4. |
| Time Frame | Baseline and Cycle 1 Day 8, Cycle 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants with evaluable CTCs at both baseline and Cycle 1 Day 8, and evaluable PSA result at both baseline and Cycle 4 |
| Arm/Group Title | Overall Population (Treatment A or Treatment B) |
|---|---|
| Arm/Group Description | Docetaxel 75 mg/m^2 or Cabazitaxel 25 mg/m^2 IV infusion on Day 1 of Cycle 1 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily. Participants with <30% PSA reduction from baseline at the end of Cycle 4, switched to Cabazitaxel 25 mg/m^2 IV or Docetaxel 75mg/m^2 IV infusion respectively on Day 1 of Cycle 5 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, death, unacceptable toxicity or participant's refusal of further study treatment. Participants with ≥30% PSA reduction from baseline at the end of Cycle 4, continued on the same treatment which they received before switching until DP, death, unacceptable toxicity or participant's refusal of further study treatment. |
| Measure Participants | 19 |
| PSA decreased ≥30% at Cycle 4 |
0.69
(0.87)
|
| PSA not decreased ≥30% at Cycle 4 |
0.09
(0.18)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Overall Population (Treatment A or Treatment B) |
|---|---|---|
| Comments | MTB change from baseline at Cycle 1 Day 8 in participants with ≥30% decrease in PSA at Cycle 4 was compared with that of participants who did not have ≥30% decrease in PSA at Cycle 4 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0927 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
Adverse Events
| Time Frame | ||||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Reported AEs are treatment emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the time of first dose until 30 days after the last treatment administration). Safety population includes all treated participants. | |||||
| Arm/Group Title | Docetaxel + Prednisone (Treatment A) - Throughout | Cabazitaxel + Prednisone (Treatment B) - Throughout | Switched Population (Treatment A to B or Treatment B to A) | |||
| Arm/Group Description | Docetaxel 75 mg/m^2 IV infusion on Day 1 of Cycle 1 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily. Participants with ≥30% PSA reduction from baseline at the end of Cycle 4, continued on the same treatment throughout until DP, death, unacceptable toxicity or participant's refusal of further study treatment. | Cabazitaxel 25 mg/m^2 IV infusion on Day 1 of Cycle 1 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily. Participants with ≥30% PSA reduction from baseline at the end of Cycle 4, continued on the same treatment throughout until DP, death, unacceptable toxicity or participant's refusal of further study treatment. | Docetaxel 75 mg/m^2 or Cabazitaxel 25 mg/m^2 IV infusion on Day 1 of Cycle 1 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily. Participants with <30% PSA reduction from baseline at the end of Cycle 4 switched to Cabazitaxel 25 mg/m^2 IV or Docetaxel 75mg/m^2 IV infusion respectively on Day 1 of Cycle 5 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, death, unacceptable toxicity or participant's refusal of further study treatment. | |||
All Cause Mortality |
||||||
| Docetaxel + Prednisone (Treatment A) - Throughout | Cabazitaxel + Prednisone (Treatment B) - Throughout | Switched Population (Treatment A to B or Treatment B to A) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Docetaxel + Prednisone (Treatment A) - Throughout | Cabazitaxel + Prednisone (Treatment B) - Throughout | Switched Population (Treatment A to B or Treatment B to A) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 10/27 (37%) | 8/19 (42.1%) | 9/15 (60%) | |||
| Blood and lymphatic system disorders | ||||||
| Febrile neutropenia | 3/27 (11.1%) | 2/19 (10.5%) | 0/15 (0%) | |||
| Anaemia | 0/27 (0%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Neutropenia | 1/27 (3.7%) | 0/19 (0%) | 0/15 (0%) | |||
| Cardiac disorders | ||||||
| Atrial fibrillation | 1/27 (3.7%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Myocardial infarction | 1/27 (3.7%) | 0/19 (0%) | 0/15 (0%) | |||
| Supraventricular tachycardia | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal pain | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Diarrhoea | 0/27 (0%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Pneumoperitoneum | 1/27 (3.7%) | 0/19 (0%) | 0/15 (0%) | |||
| General disorders | ||||||
| Asthenia | 1/27 (3.7%) | 0/19 (0%) | 0/15 (0%) | |||
| Disease progression | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Localised oedema | 1/27 (3.7%) | 0/19 (0%) | 0/15 (0%) | |||
| Immune system disorders | ||||||
| Anaphylactoid reaction | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Infections and infestations | ||||||
| Urinary tract infection | 0/27 (0%) | 2/19 (10.5%) | 1/15 (6.7%) | |||
| Sepsis | 0/27 (0%) | 2/19 (10.5%) | 0/15 (0%) | |||
| Bronchitis | 1/27 (3.7%) | 0/19 (0%) | 0/15 (0%) | |||
| Pneumonia | 1/27 (3.7%) | 0/19 (0%) | 0/15 (0%) | |||
| Septic shock | 1/27 (3.7%) | 0/19 (0%) | 0/15 (0%) | |||
| Urosepsis | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Injury, poisoning and procedural complications | ||||||
| Hip fracture | 2/27 (7.4%) | 0/19 (0%) | 0/15 (0%) | |||
| Spinal compression fracture | 0/27 (0%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Investigations | ||||||
| White blood cell count decreased | 1/27 (3.7%) | 0/19 (0%) | 0/15 (0%) | |||
| Metabolism and nutrition disorders | ||||||
| Hyperglycaemia | 0/27 (0%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Nervous system disorders | ||||||
| Nerve compression | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Nerve root compression | 1/27 (3.7%) | 0/19 (0%) | 0/15 (0%) | |||
| Renal and urinary disorders | ||||||
| Acute kidney injury | 0/27 (0%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Haematuria | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Urinary retention | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Pulmonary embolism | 0/27 (0%) | 1/19 (5.3%) | 1/15 (6.7%) | |||
| Dyspnoea | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Pleural effusion | 0/27 (0%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Vascular disorders | ||||||
| Deep vein thrombosis | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Docetaxel + Prednisone (Treatment A) - Throughout | Cabazitaxel + Prednisone (Treatment B) - Throughout | Switched Population (Treatment A to B or Treatment B to A) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 26/27 (96.3%) | 18/19 (94.7%) | 15/15 (100%) | |||
| Blood and lymphatic system disorders | ||||||
| Febrile neutropenia | 2/27 (7.4%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Neutropenia | 0/27 (0%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Cardiac disorders | ||||||
| Sinus tachycardia | 1/27 (3.7%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Arrhythmia | 0/27 (0%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Palpitations | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Tachycardia | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Ear and labyrinth disorders | ||||||
| Hearing impaired | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Eye disorders | ||||||
| Lacrimation increased | 5/27 (18.5%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Vitreous haemorrhage | 2/27 (7.4%) | 0/19 (0%) | 0/15 (0%) | |||
| Dry eye | 0/27 (0%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Vision blurred | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Visual acuity reduced | 0/27 (0%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Vitreous floaters | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Gastrointestinal disorders | ||||||
| Diarrhoea | 13/27 (48.1%) | 12/19 (63.2%) | 9/15 (60%) | |||
| Nausea | 8/27 (29.6%) | 10/19 (52.6%) | 7/15 (46.7%) | |||
| Abdominal pain | 7/27 (25.9%) | 4/19 (21.1%) | 4/15 (26.7%) | |||
| Constipation | 3/27 (11.1%) | 6/19 (31.6%) | 5/15 (33.3%) | |||
| Vomiting | 3/27 (11.1%) | 7/19 (36.8%) | 4/15 (26.7%) | |||
| Dyspepsia | 3/27 (11.1%) | 3/19 (15.8%) | 3/15 (20%) | |||
| Haemorrhoids | 0/27 (0%) | 2/19 (10.5%) | 2/15 (13.3%) | |||
| Proctalgia | 0/27 (0%) | 0/19 (0%) | 3/15 (20%) | |||
| Stomatitis | 2/27 (7.4%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Faeces soft | 0/27 (0%) | 0/19 (0%) | 2/15 (13.3%) | |||
| Gastrooesophageal reflux disease | 0/27 (0%) | 1/19 (5.3%) | 1/15 (6.7%) | |||
| Oral pain | 1/27 (3.7%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Abdominal pain lower | 0/27 (0%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Dry mouth | 0/27 (0%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Dysphagia | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Flatulence | 0/27 (0%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Haematochezia | 0/27 (0%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Lower gastrointestinal haemorrhage | 0/27 (0%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Melaena | 0/27 (0%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Rectal haemorrhage | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Salivary hypersecretion | 0/27 (0%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Tongue discolouration | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
| General disorders | ||||||
| Fatigue | 18/27 (66.7%) | 13/19 (68.4%) | 10/15 (66.7%) | |||
| Oedema peripheral | 7/27 (25.9%) | 3/19 (15.8%) | 4/15 (26.7%) | |||
| Pyrexia | 3/27 (11.1%) | 2/19 (10.5%) | 1/15 (6.7%) | |||
| Asthenia | 3/27 (11.1%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Hyperthermia | 3/27 (11.1%) | 0/19 (0%) | 0/15 (0%) | |||
| Chills | 2/27 (7.4%) | 0/19 (0%) | 0/15 (0%) | |||
| Adverse drug reaction | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Disease progression | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Exercise tolerance decreased | 0/27 (0%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Facial pain | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Infusion site extravasation | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Non-cardiac chest pain | 0/27 (0%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Pain | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Peripheral swelling | 0/27 (0%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Temperature intolerance | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Hepatobiliary disorders | ||||||
| Hepatomegaly | 0/27 (0%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Infections and infestations | ||||||
| Urinary tract infection | 1/27 (3.7%) | 3/19 (15.8%) | 2/15 (13.3%) | |||
| Upper respiratory tract infection | 2/27 (7.4%) | 1/19 (5.3%) | 2/15 (13.3%) | |||
| Bronchopneumonia | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Catheter site cellulitis | 0/27 (0%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Enterobacter infection | 0/27 (0%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Fungal skin infection | 0/27 (0%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Gastroenteritis viral | 0/27 (0%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Oral fungal infection | 0/27 (0%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Pneumonia | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Sepsis | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Septic phlebitis | 0/27 (0%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Tooth infection | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Injury, poisoning and procedural complications | ||||||
| Fall | 1/27 (3.7%) | 2/19 (10.5%) | 2/15 (13.3%) | |||
| Infusion related reaction | 3/27 (11.1%) | 0/19 (0%) | 0/15 (0%) | |||
| Contusion | 0/27 (0%) | 0/19 (0%) | 2/15 (13.3%) | |||
| Arthropod bite | 0/27 (0%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Skin abrasion | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Spinal compression fracture | 0/27 (0%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Investigations | ||||||
| Weight decreased | 1/27 (3.7%) | 3/19 (15.8%) | 1/15 (6.7%) | |||
| Blood creatinine increased | 1/27 (3.7%) | 2/19 (10.5%) | 0/15 (0%) | |||
| Weight increased | 2/27 (7.4%) | 0/19 (0%) | 0/15 (0%) | |||
| Blood pressure increased | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 8/27 (29.6%) | 4/19 (21.1%) | 4/15 (26.7%) | |||
| Dehydration | 0/27 (0%) | 1/19 (5.3%) | 1/15 (6.7%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Back pain | 5/27 (18.5%) | 6/19 (31.6%) | 4/15 (26.7%) | |||
| Pain in extremity | 6/27 (22.2%) | 3/19 (15.8%) | 4/15 (26.7%) | |||
| Arthralgia | 3/27 (11.1%) | 3/19 (15.8%) | 4/15 (26.7%) | |||
| Muscular weakness | 4/27 (14.8%) | 0/19 (0%) | 3/15 (20%) | |||
| Musculoskeletal chest pain | 2/27 (7.4%) | 2/19 (10.5%) | 1/15 (6.7%) | |||
| Musculoskeletal pain | 1/27 (3.7%) | 2/19 (10.5%) | 1/15 (6.7%) | |||
| Myalgia | 3/27 (11.1%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Muscle spasms | 2/27 (7.4%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Neck pain | 2/27 (7.4%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Musculoskeletal stiffness | 0/27 (0%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Oncologic complication | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Nervous system disorders | ||||||
| Neuropathy peripheral | 9/27 (33.3%) | 6/19 (31.6%) | 3/15 (20%) | |||
| Dizziness | 3/27 (11.1%) | 3/19 (15.8%) | 3/15 (20%) | |||
| Dysgeusia | 4/27 (14.8%) | 2/19 (10.5%) | 3/15 (20%) | |||
| Paraesthesia | 3/27 (11.1%) | 2/19 (10.5%) | 3/15 (20%) | |||
| Headache | 3/27 (11.1%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Peripheral sensory neuropathy | 2/27 (7.4%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Hypoaesthesia | 1/27 (3.7%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Aphonia | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Burning sensation | 0/27 (0%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Nerve compression | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Syncope | 0/27 (0%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Psychiatric disorders | ||||||
| Insomnia | 3/27 (11.1%) | 2/19 (10.5%) | 3/15 (20%) | |||
| Agitation | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Depression | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Renal and urinary disorders | ||||||
| Haematuria | 1/27 (3.7%) | 2/19 (10.5%) | 5/15 (33.3%) | |||
| Dysuria | 1/27 (3.7%) | 1/19 (5.3%) | 2/15 (13.3%) | |||
| Urinary incontinence | 2/27 (7.4%) | 1/19 (5.3%) | 1/15 (6.7%) | |||
| Pollakiuria | 1/27 (3.7%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Urinary tract pain | 1/27 (3.7%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Bladder spasm | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Cystitis noninfective | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Hydronephrosis | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Hypertonic bladder | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Urinary retention | 0/27 (0%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Reproductive system and breast disorders | ||||||
| Pelvic pain | 2/27 (7.4%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Penile pain | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Scrotal oedema | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 7/27 (25.9%) | 4/19 (21.1%) | 2/15 (13.3%) | |||
| Dyspnoea | 6/27 (22.2%) | 1/19 (5.3%) | 2/15 (13.3%) | |||
| Epistaxis | 5/27 (18.5%) | 1/19 (5.3%) | 2/15 (13.3%) | |||
| Oropharyngeal pain | 2/27 (7.4%) | 3/19 (15.8%) | 0/15 (0%) | |||
| Nasal congestion | 2/27 (7.4%) | 1/19 (5.3%) | 1/15 (6.7%) | |||
| Productive cough | 1/27 (3.7%) | 2/19 (10.5%) | 0/15 (0%) | |||
| Upper-airway cough syndrome | 0/27 (0%) | 1/19 (5.3%) | 1/15 (6.7%) | |||
| Wheezing | 0/27 (0%) | 2/19 (10.5%) | 0/15 (0%) | |||
| Dyspnoea exertional | 0/27 (0%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Increased upper airway secretion | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Nasal obstruction | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Pulmonary embolism | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Respiratory distress | 0/27 (0%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Alopecia | 9/27 (33.3%) | 5/19 (26.3%) | 5/15 (33.3%) | |||
| Nail ridging | 2/27 (7.4%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Dry skin | 1/27 (3.7%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Erythema | 2/27 (7.4%) | 0/19 (0%) | 0/15 (0%) | |||
| Nail discolouration | 1/27 (3.7%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Actinic keratosis | 0/27 (0%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Nail disorder | 0/27 (0%) | 0/19 (0%) | 1/15 (6.7%) | |||
| Nail hypertrophy | 0/27 (0%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Night sweats | 0/27 (0%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Petechiae | 0/27 (0%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Rash maculo-papular | 0/27 (0%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Skin tightness | 0/27 (0%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Skin ulcer | 0/27 (0%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Vascular disorders | ||||||
| Hypotension | 3/27 (11.1%) | 2/19 (10.5%) | 0/15 (0%) | |||
| Flushing | 1/27 (3.7%) | 0/19 (0%) | 2/15 (13.3%) | |||
| Hypertension | 1/27 (3.7%) | 1/19 (5.3%) | 1/15 (6.7%) | |||
| Hot flush | 2/27 (7.4%) | 0/19 (0%) | 0/15 (0%) | |||
| Deep vein thrombosis | 0/27 (0%) | 1/19 (5.3%) | 0/15 (0%) | |||
| Pallor | 0/27 (0%) | 1/19 (5.3%) | 0/15 (0%) | |||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
Results Point of Contact
| Name/Title | Trial Transparency Team |
|---|---|
| Organization | Sanofi |
| Phone | |
| Contact-US@sanofi.com |
- CABAZL06056
- U1111-1130-9893