Trial Outcomes & Findings for Ibrutinib as Neoadjuvant Therapy in Localized Prostate Cancer (NCT NCT02643667)

Last Updated: 2025-01-08

Results Overview

* CTCAE v.4.0 * DLTs will be defined as any of the following that are attributable to ibrutinib. * Any grade 4 toxicity, including hematologic toxicities with the exception of lymphocytosis. Lymphocytosis, in the absence of clinical symptoms, is excluded from DLT, as this may be considered an on-target pharmacodynamics effect of BTK inhibition. * Any grade 3 toxicity. * Any recurrence of the same grade 3 toxicity. * Any delay of RP due to study-drug related toxicity. * Any complications of RP (e.g., bleeding, delayed wound healing) deemed to be related to study drug.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

27 participants

Primary outcome timeframe

Completion of DLT follow-up (2 weeks for Phase I portion and 28 days for Safety Run-In)

Results posted on

2025-01-08

Participant Flow

Participant milestones

Participant milestones
Measure	Phase I: Ibrutinib * Ibrutinib 840 mg by mouth once daily for 2 weeks. * Radical prostatectomy will be performed at least 7 days but not more than 12 days following the last scheduled dose of ibrutinib.	Safety Run-In and Phase II: Ibrutinib * Ibrutinib 840 mg by mouth once daily for 4 weeks. * Radical prostatectomy will be performed at least 7 days but not more than 12 days following the last scheduled dose of ibrutinib
Overall Study STARTED	3	24
Overall Study COMPLETED	3	24
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Ibrutinib as Neoadjuvant Therapy in Localized Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase I: Ibrutinib n=3 Participants * Ibrutinib 840 mg by mouth once daily for 2 weeks. * Radical prostatectomy will be performed at least 7 days but not more than 12 days following the last scheduled dose of ibrutinib.	Safety Run-In and Phase II: Ibrutinib n=24 Participants * Ibrutinib 840 mg by mouth once daily for 4 weeks. * Radical prostatectomy will be performed at least 7 days but not more than 12 days following the last scheduled dose of ibrutinib	Total n=27 Participants Total of all reporting groups
Age, Continuous	61 years n=5 Participants	62.5 years n=7 Participants	61 years 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	3 Participants n=5 Participants	24 Participants n=7 Participants	27 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	24 Participants n=7 Participants	27 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 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	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	24 Participants n=7 Participants	27 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 United States	3 participants n=5 Participants	24 participants n=7 Participants	27 participants n=5 Participants

PRIMARY outcome

Timeframe: Completion of DLT follow-up (2 weeks for Phase I portion and 28 days for Safety Run-In)

Population: Only participants enrolled in the Phase I portion and the 6 participants in the Safety Run-In portion of the Phase II portion are evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Phase I: Ibrutinib n=3 Participants * Ibrutinib 840 mg by mouth once daily for 2 weeks. * Radical prostatectomy will be performed at least 7 days but not more than 12 days following the last scheduled dose of ibrutinib.	Safety Run-In and Phase II: Ibrutinib n=6 Participants * Ibrutinib 840 mg by mouth once daily for 4 weeks. * Radical prostatectomy will be performed at least 7 days but not more than 12 days following the last scheduled dose of ibrutinib
Number of Participants With Dose Limiting Toxicities (Phase I and Safety Run-In)	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Pre-treatment and at time of RP (approximately 10 weeks after start of treatment)

Population: Only those in the Safety Run-In and Phase II portion were evaluable for this outcome measure. Additional participants in the Safety Run-In were not analyzed for this outcome measure due to either missing sample or too few cells in the sample to analyze. The investigators were unable to analyze matched/paired samples due to sample processing issues with the enrolled patients diagnostic biopsies (not enough evaluable tissue or unable to obtain biopsy tissue from outside medical center).

In pre-treatment biopsy, RP tissue, and reference RP tissue quantitated by immunohistochemistry (IHC). Patients will be considered to have a positive response if there is \>2 fold decrease from pre-treatment to post-treatment, or considered to have a negative response if there is \<2 fold decrease. The percentage of participants who have "positive" responses are represented in the outcome measure data.

Outcome measures

Outcome measures
Measure	Phase I: Ibrutinib * Ibrutinib 840 mg by mouth once daily for 2 weeks. * Radical prostatectomy will be performed at least 7 days but not more than 12 days following the last scheduled dose of ibrutinib.	Safety Run-In and Phase II: Ibrutinib n=15 Participants * Ibrutinib 840 mg by mouth once daily for 4 weeks. * Radical prostatectomy will be performed at least 7 days but not more than 12 days following the last scheduled dose of ibrutinib
Percentage of Participants With Positive Responses - CD20+ B Cells, IL-10+ B Cells, CD3+ T Cells, CD8+ Cytotoxic T Cells, Effector CD4+FOXP3- T Cells, and CD4+FOX3+ T Regulatory Cells CD20+ B cells	—	53.8 percentage of participants
Percentage of Participants With Positive Responses - CD20+ B Cells, IL-10+ B Cells, CD3+ T Cells, CD8+ Cytotoxic T Cells, Effector CD4+FOXP3- T Cells, and CD4+FOX3+ T Regulatory Cells IL10+ B cells	—	40 percentage of participants
Percentage of Participants With Positive Responses - CD20+ B Cells, IL-10+ B Cells, CD3+ T Cells, CD8+ Cytotoxic T Cells, Effector CD4+FOXP3- T Cells, and CD4+FOX3+ T Regulatory Cells CD3+ T cells	—	7.1 percentage of participants
Percentage of Participants With Positive Responses - CD20+ B Cells, IL-10+ B Cells, CD3+ T Cells, CD8+ Cytotoxic T Cells, Effector CD4+FOXP3- T Cells, and CD4+FOX3+ T Regulatory Cells CD8+ T cells	—	0 percentage of participants
Percentage of Participants With Positive Responses - CD20+ B Cells, IL-10+ B Cells, CD3+ T Cells, CD8+ Cytotoxic T Cells, Effector CD4+FOXP3- T Cells, and CD4+FOX3+ T Regulatory Cells CD4+ Foxp3- T cells	—	0 percentage of participants
Percentage of Participants With Positive Responses - CD20+ B Cells, IL-10+ B Cells, CD3+ T Cells, CD8+ Cytotoxic T Cells, Effector CD4+FOXP3- T Cells, and CD4+FOX3+ T Regulatory Cells CD4+ Foxp3+ T cells	—	13.3 percentage of participants

PRIMARY outcome

Timeframe: At RP (approximately 10 weeks after start of treatment)

Participants will be considered to have a positive response if there is \>2 fold decrease (0.5 or less B cell fold change) or considered to have a negative response if there is \<2 fold decrease. Descriptive statistics will be used to describe pre-treatment biopsy immune infiltration, post-treatment RP immune infiltration, and immune infiltration of reference RP tissue.

Outcome measures

Outcome measures
Measure	Phase I: Ibrutinib * Ibrutinib 840 mg by mouth once daily for 2 weeks. * Radical prostatectomy will be performed at least 7 days but not more than 12 days following the last scheduled dose of ibrutinib.	Safety Run-In and Phase II: Ibrutinib n=13 Participants * Ibrutinib 840 mg by mouth once daily for 4 weeks. * Radical prostatectomy will be performed at least 7 days but not more than 12 days following the last scheduled dose of ibrutinib
Mean B Cell Fold Change of CD20+ B Cells	—	0.9 B cell fold change Interval 0.3 to 1.5

SECONDARY outcome

Timeframe: Pre-treatment to RP (approximately 10 weeks after start of treatment)

Patients will be considered to have a positive response if there is \>2 fold decrease from pre-treatment to post-treatment, or considered to have a negative response if there is \<2 fold decrease. The percentage of partcipants who have "positive" responses are represented in the outcome measure data.

Outcome measures

Outcome measures
Measure	Phase I: Ibrutinib * Ibrutinib 840 mg by mouth once daily for 2 weeks. * Radical prostatectomy will be performed at least 7 days but not more than 12 days following the last scheduled dose of ibrutinib.	Safety Run-In and Phase II: Ibrutinib n=21 Participants * Ibrutinib 840 mg by mouth once daily for 4 weeks. * Radical prostatectomy will be performed at least 7 days but not more than 12 days following the last scheduled dose of ibrutinib
Percentage of Participants With Positive Responses - CD19+ B Cells, CD25^highCD27^highCD86^High B Regulatory Cells, and CD3+, CD8+, CD4+FOXP3- and CD4+FOXP3+ T Cells Induced by Neoadjuvant Ibrutinib in Patients by Flow Cytometry CD19+ B cells	—	38.1 percentage of participants
Percentage of Participants With Positive Responses - CD19+ B Cells, CD25^highCD27^highCD86^High B Regulatory Cells, and CD3+, CD8+, CD4+FOXP3- and CD4+FOXP3+ T Cells Induced by Neoadjuvant Ibrutinib in Patients by Flow Cytometry CD25+CD27+CD86+ regulatory B cells	—	35 percentage of participants
Percentage of Participants With Positive Responses - CD19+ B Cells, CD25^highCD27^highCD86^High B Regulatory Cells, and CD3+, CD8+, CD4+FOXP3- and CD4+FOXP3+ T Cells Induced by Neoadjuvant Ibrutinib in Patients by Flow Cytometry CD3+ T cells	—	14.3 percentage of participants
Percentage of Participants With Positive Responses - CD19+ B Cells, CD25^highCD27^highCD86^High B Regulatory Cells, and CD3+, CD8+, CD4+FOXP3- and CD4+FOXP3+ T Cells Induced by Neoadjuvant Ibrutinib in Patients by Flow Cytometry CD8+ T cells	—	9.5 percentage of participants
Percentage of Participants With Positive Responses - CD19+ B Cells, CD25^highCD27^highCD86^High B Regulatory Cells, and CD3+, CD8+, CD4+FOXP3- and CD4+FOXP3+ T Cells Induced by Neoadjuvant Ibrutinib in Patients by Flow Cytometry CD4+ Foxp3- T cells	—	14.3 percentage of participants
Percentage of Participants With Positive Responses - CD19+ B Cells, CD25^highCD27^highCD86^High B Regulatory Cells, and CD3+, CD8+, CD4+FOXP3- and CD4+FOXP3+ T Cells Induced by Neoadjuvant Ibrutinib in Patients by Flow Cytometry CD4+ Foxp3+ T cells	—	14.3 percentage of participants

SECONDARY outcome

Timeframe: At baseline and approximately day 29

Population: If participants did not have the day 29 PSA drawn then they are not included in the overall number of participants analyzed.

Outcome measures

Outcome measures
Measure	Phase I: Ibrutinib n=3 Participants * Ibrutinib 840 mg by mouth once daily for 2 weeks. * Radical prostatectomy will be performed at least 7 days but not more than 12 days following the last scheduled dose of ibrutinib.	Safety Run-In and Phase II: Ibrutinib n=23 Participants * Ibrutinib 840 mg by mouth once daily for 4 weeks. * Radical prostatectomy will be performed at least 7 days but not more than 12 days following the last scheduled dose of ibrutinib
Number of Participants Who Had a 50% or Greater Decline in PSA	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Completion of follow-up (approximately 10 weeks after start of treatment)

Population: Only participants in the Safety Lead-In and Phase II portion of the study who had a radical RP are evaluable for this outcome measure.

Pathologic down-staging and/or pathologic T0

Outcome measures

Outcome measures
Measure	Phase I: Ibrutinib * Ibrutinib 840 mg by mouth once daily for 2 weeks. * Radical prostatectomy will be performed at least 7 days but not more than 12 days following the last scheduled dose of ibrutinib.	Safety Run-In and Phase II: Ibrutinib n=21 Participants * Ibrutinib 840 mg by mouth once daily for 4 weeks. * Radical prostatectomy will be performed at least 7 days but not more than 12 days following the last scheduled dose of ibrutinib
Number of Participants With a Treatment Response (Safety Lead-In and Phase II Only)	—	7 Participants

Adverse Events

Phase I: Ibrutinib

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Safety Run-In and Phase II: Ibrutinib

Serious events: 5 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Phase I: Ibrutinib n=3 participants at risk * Ibrutinib 840 mg by mouth once daily for 2 weeks. * Radical prostatectomy will be performed at least 7 days but not more than 12 days following the last scheduled dose of ibrutinib.	Safety Run-In and Phase II: Ibrutinib n=24 participants at risk * Ibrutinib 840 mg by mouth once daily for 4 weeks. * Radical prostatectomy will be performed at least 7 days but not more than 12 days following the last scheduled dose of ibrutinib
Gastrointestinal disorders Abdominal pain	0.00% 0/3 • - Adverse events were collected from start of treatment until 30 days after the end of treatment (up to a total of 6 weeks for Phase I portion and up to 2 months for Safety Run-In and Phase II portion). - All-cause mortality was collected from start of treatment until completion of follow-up (up to week 10, approximately day 64).	4.2% 1/24 • - Adverse events were collected from start of treatment until 30 days after the end of treatment (up to a total of 6 weeks for Phase I portion and up to 2 months for Safety Run-In and Phase II portion). - All-cause mortality was collected from start of treatment until completion of follow-up (up to week 10, approximately day 64).
General disorders Fever	0.00% 0/3 • - Adverse events were collected from start of treatment until 30 days after the end of treatment (up to a total of 6 weeks for Phase I portion and up to 2 months for Safety Run-In and Phase II portion). - All-cause mortality was collected from start of treatment until completion of follow-up (up to week 10, approximately day 64).	4.2% 1/24 • - Adverse events were collected from start of treatment until 30 days after the end of treatment (up to a total of 6 weeks for Phase I portion and up to 2 months for Safety Run-In and Phase II portion). - All-cause mortality was collected from start of treatment until completion of follow-up (up to week 10, approximately day 64).
Investigations Alanine aminotransferase increased	0.00% 0/3 • - Adverse events were collected from start of treatment until 30 days after the end of treatment (up to a total of 6 weeks for Phase I portion and up to 2 months for Safety Run-In and Phase II portion). - All-cause mortality was collected from start of treatment until completion of follow-up (up to week 10, approximately day 64).	4.2% 1/24 • - Adverse events were collected from start of treatment until 30 days after the end of treatment (up to a total of 6 weeks for Phase I portion and up to 2 months for Safety Run-In and Phase II portion). - All-cause mortality was collected from start of treatment until completion of follow-up (up to week 10, approximately day 64).
Investigations Aspartate aminotransferase increased	0.00% 0/3 • - Adverse events were collected from start of treatment until 30 days after the end of treatment (up to a total of 6 weeks for Phase I portion and up to 2 months for Safety Run-In and Phase II portion). - All-cause mortality was collected from start of treatment until completion of follow-up (up to week 10, approximately day 64).	4.2% 1/24 • - Adverse events were collected from start of treatment until 30 days after the end of treatment (up to a total of 6 weeks for Phase I portion and up to 2 months for Safety Run-In and Phase II portion). - All-cause mortality was collected from start of treatment until completion of follow-up (up to week 10, approximately day 64).
Investigations Lymphocyte count decreased	0.00% 0/3 • - Adverse events were collected from start of treatment until 30 days after the end of treatment (up to a total of 6 weeks for Phase I portion and up to 2 months for Safety Run-In and Phase II portion). - All-cause mortality was collected from start of treatment until completion of follow-up (up to week 10, approximately day 64).	4.2% 1/24 • - Adverse events were collected from start of treatment until 30 days after the end of treatment (up to a total of 6 weeks for Phase I portion and up to 2 months for Safety Run-In and Phase II portion). - All-cause mortality was collected from start of treatment until completion of follow-up (up to week 10, approximately day 64).
Investigations Platelet count decreased	0.00% 0/3 • - Adverse events were collected from start of treatment until 30 days after the end of treatment (up to a total of 6 weeks for Phase I portion and up to 2 months for Safety Run-In and Phase II portion). - All-cause mortality was collected from start of treatment until completion of follow-up (up to week 10, approximately day 64).	4.2% 1/24 • - Adverse events were collected from start of treatment until 30 days after the end of treatment (up to a total of 6 weeks for Phase I portion and up to 2 months for Safety Run-In and Phase II portion). - All-cause mortality was collected from start of treatment until completion of follow-up (up to week 10, approximately day 64).
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/3 • - Adverse events were collected from start of treatment until 30 days after the end of treatment (up to a total of 6 weeks for Phase I portion and up to 2 months for Safety Run-In and Phase II portion). - All-cause mortality was collected from start of treatment until completion of follow-up (up to week 10, approximately day 64).	4.2% 1/24 • - Adverse events were collected from start of treatment until 30 days after the end of treatment (up to a total of 6 weeks for Phase I portion and up to 2 months for Safety Run-In and Phase II portion). - All-cause mortality was collected from start of treatment until completion of follow-up (up to week 10, approximately day 64).
Vascular disorders Hematoma	0.00% 0/3 • - Adverse events were collected from start of treatment until 30 days after the end of treatment (up to a total of 6 weeks for Phase I portion and up to 2 months for Safety Run-In and Phase II portion). - All-cause mortality was collected from start of treatment until completion of follow-up (up to week 10, approximately day 64).	4.2% 1/24 • - Adverse events were collected from start of treatment until 30 days after the end of treatment (up to a total of 6 weeks for Phase I portion and up to 2 months for Safety Run-In and Phase II portion). - All-cause mortality was collected from start of treatment until completion of follow-up (up to week 10, approximately day 64).
Vascular disorders Lymphocele	0.00% 0/3 • - Adverse events were collected from start of treatment until 30 days after the end of treatment (up to a total of 6 weeks for Phase I portion and up to 2 months for Safety Run-In and Phase II portion). - All-cause mortality was collected from start of treatment until completion of follow-up (up to week 10, approximately day 64).	4.2% 1/24 • - Adverse events were collected from start of treatment until 30 days after the end of treatment (up to a total of 6 weeks for Phase I portion and up to 2 months for Safety Run-In and Phase II portion). - All-cause mortality was collected from start of treatment until completion of follow-up (up to week 10, approximately day 64).

Other adverse events

Additional Information

Dr. Russell K. Pachynski

Washington University School of Medicine

Phone: 314-286-2341

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place