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Study to Evaluate Ibrutinib Combination Therapy in Patients With Selected Gastrointestinal and Genitourinary Tumors

Primary Purpose

Metastatic Renal Cell Carcinoma, Advanced Urothelial Carcinoma, Advanced Gastric Adenocarcinoma

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
ibrutinib
everolimus
paclitaxel
docetaxel
cetuximab
pembrolizumab
Sponsored by
Pharmacyclics LLC.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Renal Cell Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Sites / Locations

  • Clearview Cancer Institute /ID# 1128-0965
  • Banner MD Anderson Cancer Center /ID# 1128-0802
  • University of Arizona Cancer Center - Tucson /ID# 1128-1546
  • Alta Bates Comprehensive Cancer Center /ID# 1128-0135
  • St Marys Medical Center /ID# 1128-0969
  • Duplicate_University of California San Diego/ Moores Cancer Center /ID# 1128-0241
  • VA Long Beach Healthcare System /ID# 1128-0480
  • USC Norris Cancer Center /ID# 1128-0209
  • UC Irvine Medical Center - Chao Family Comprehensive Cancer Center /ID# 1128-0008
  • Gregory Smith, MD (Private Practice) /ID# 1128-0419
  • Salinas Valley Memorial Hosp /ID# 1128-0482
  • Premiere Oncology, A Medical Corporation /ID# 1128-1085
  • St. Joseph Health /ID# 1128-1462
  • Whittingham Cancer Center at Norwalk Hospital /ID# 1128-0411
  • Georgetown University Hospital /ID# 1128-0824
  • Duplicate_Cancer Specialist of North Florida (CSNF) ( R ) /ID# 1128-1093
  • IACT Health-Columbus /ID# 1128-1389
  • Northshore Kellogg Cancer Center /ID# 1128-0484
  • Franciscan Health Indianapolis /ID# 1128-1125
  • Horizon Oncology Research Center /ID# 1128-0337
  • University of Iowa Hospitals and Clinics /ID# 1128-0766
  • The University of Kansas Cancer Center /ID# 1128-0706
  • East Jefferson General Hospital /ID# 1128-1084
  • Duplicate_Tufts Medical Center /ID# 1128-0016
  • Barbara Ann Karmanos Cancer In /ID# 1128-0130
  • Henry Ford Hospital /ID# 1128-0195
  • Central Care Cancer Center /ID# 1128-1596
  • Capital Region Medical Center /ID# 1128-1412
  • Nebraska Methodist Hospital /ID# 1128-0229
  • New Jersey Center for Cancer Research /ID# 1128-0493
  • Duplicate_New Mexico Cancer Care Alliance /ID# 1128-0938
  • San Juan Oncology Associates /ID# 1128-1020
  • Memorial Sloan Kettering Cancer Center-Koch Center /ID# 1128-0091
  • Wake Forest Univ HS /ID# 1128-0975
  • Oregon Health & Science University /ID# 1128-0251
  • Penn State Hershey Medical Ctr /ID# 1128-0220
  • Abramson Cancer Center of the Univ. of Pennsylvania /ID# 1128-0402
  • Vanderbilt Infectious Disease Clinic /ID# 1128-0024
  • The University of Texas Medical Branch (UTMB) - Cancer Center - Galves /ID# 1128-0974
  • Duplicate_Scott & White Mem Hosp & Clin /ID# 1128-0046
  • Duplicate_Virginia Cancer Specialists - Fairfax Office /ID# 1128-0972
  • Virginia Mason Medical Center /ID# 1128-0005
  • University of Washington /ID# 1128-1382
  • Confluence Health /ID# 1128-0894
  • Seoul National University Bundang Hospital /ID# 1128-0982
  • Yonsei University Health System Severance Hospital /ID# 1128-0927
  • Chonnam National University Hwasun Hospital /ID# 1128-0916
  • Seoul National University Hospital /ID# 1128-0926
  • Asan Medical Center /ID# 1128-0963
  • Samsung Medical Center /ID# 1128-0925
  • The Catholic University of Korea, Seoul St. Mary's Hospital /ID# 1128-0928
  • Korea University Guro Hospital /ID# 1128-0924
  • Instituto Catalan de Oncologia (ICO) Badalona /ID# 1128-0984
  • Hospital Unversitario Marques de Valdecilla /ID# 1128-0973
  • Hospital Universitario Vall d'Hebron /ID# 1128-0534
  • Hospital Clinic de Barcelona /ID# 1128-0533
  • Hospital Universitario Ramon y Cajal /ID# 1128-0874
  • Hospital Universitario 12 de Octubre /ID# 1128-0864
  • Hospital Universitario La Paz /ID# 1128-0921
  • Hospital Universitario Virgen del Rocio /ID# 1128-0863
  • Sarah Cannon Research Institute /ID# 1128-1079
  • Duplicate_Beatson west of scotland cancer center /ID# 1128-0652
  • The Royal Marsden NHS Foundation Trust /ID# 1128-0543
  • The Christie Hospital /ID# 1128-0030
  • Duplicate_Oxford University Hospitals NHS Trust /ID# 1128-0814

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Cohort 1: Renal Cell Carcinoma (RCC)

Cohort 2: Urothelial Carcinoma (UC)

Cohort 3: Gastric Adenocarcinoma (GA or GC)

Cohort 4: Colorectal Adenocarcinoma (CRC)

Cohort 5: Urothelial Carcinoma (UC) Ibrutinib

Cohort 6: Urothelial Carcinoma (UC) With Pembrolizumab

Arm Description

Phase 1b: Participants receive ibrutinib at various dose levels in combination with a fixed dose of everolimus to determine the recommended phase 2 dose (RP2D) of ibrutinib. (The RP2D was determined for each cohort separately.) Phase 2: Participants receive ibrutinib at the RP2D determined in phase 1b in combination with everolimus.

Phase 1b: Participants receive ibrutinib at various dose levels in combination with a fixed dose of paclitaxel to determine the RP2D of ibrutinib. (The RP2D was determined for each cohort separately.) Phase 2: Participants receive ibrutinib at the RP2D determined in Phase 1b in combination with paclitaxel.

Phase 1b: Participants receive ibrutinib at various dose levels in combination with a fixed dose of docetaxel to determine the RP2D of ibrutinib. (The RP2D was determined for each cohort separately.) Phase 2: Participants receive docetaxel at the RP2D determined in Phase 1b in combination with docetaxel.

Phase 1b: Participants receive ibrutinib at various dose levels in combination with a fixed dose of cetuximab to determine RP2D of ibrutinib. (The RP2D was determined for each cohort separately.) Phase 2: Participants receive ibrutinib at the RP2D determined in Phase 1b in combination with cetuximab.

Phase 1b: Participants receive ibrutinib at various dose levels to determine the RP2D of ibrutinib.(The RP2D was determined for each cohort separately.) Phase 2: Participants receive ibrutinib at the RP2D determined in Phase 1b.

Phase 1b: Participants receive ibrutinib at various dose levels in combination with a fixed dose of pembrolizumab to determine the RP2D of ibrutinib. (The RP2D was determined for each cohort separately.) Phase 2: Participants receive ibrutinib at the RP2D determined in Phase 1b in combination with pembrolizumab.

Outcomes

Primary Outcome Measures

Phase 1b: Number of Participants With Dose-Limiting Toxicities (DLTs) in Cohorts 1 to 6
A DLT was defined as any Grade 3 (severe) or higher non-hematologic or Grade 4 (life-threatening) hematologic adverse event (AE) occurring during the DLT observation period that was considered to be at least possibly related to the study treatment (ibrutinib or drug combination).
Phase 1b/2 RP2D: Progression-Free Survival (PFS) as Assessed by Investigator in Cohorts 1 and 2
PFS is defined as the time from the date of first dose of study treatment to the date of first documentation of progressive disease (PD) or date of death from any cause, whichever occurs first, regardless of the use of subsequent anti-cancer treatment. PD was defined in accordance with Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study), and an absolute increase of ≥ 5 mm, or unequivocal progression of existing non-target lesions or the appearance of new lesions.
Phase 1b/2 RP2D: Overall Response Rate (ORR) as Assessed by Investigator in Cohorts 3 to 6
ORR is defined as the percentage of participants who have a best response of partial response (PR) or complete response (CR) to therapy in accordance with RECIST 1.1 criteria. CR: The disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Normalization of tumor marker level, if relevant. All lymph nodes must be non-pathological in size (< 10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Secondary Outcome Measures

Phase 1b: ORR in Cohorts 1 to 6
ORR is defined as the percentage of participants who have a best response of partial response (PR) or complete response (CR) to therapy in accordance with RECIST 1.1 criteria. CR: The disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Normalization of tumor marker level, if relevant. All lymph nodes must be non-pathological in size (< 10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Phase 1b: Disease Control Rate (DCR) in Cohorts 1 to 6
DCR is is defined as the percentage of participants who have a best response of PR, CR, or stable disease (SD) to therapy in accordance with RECIST 1.1 criteria. CR: The disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Normalization of tumor marker level, if relevant. All lymph nodes must be non-pathological in size (< 10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD since the treatment started (baseline or after). For SD, tthere was no need for confirmation by a subsequent imaging assessment.
Phase 1b/2 RP2D: DCR in Cohorts 1 to 6
DCR is is defined as the percentage of participants who have a best response of PR, CR, or SD to therapy in accordance with RECIST 1.1 criteria. CR: The disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Normalization of tumor marker level, if relevant. All lymph nodes must be non-pathological in size (< 10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD since the treatment started (baseline or after). For SD, tthere was no need for confirmation by a subsequent imaging assessment.
Phase 1b/2 RP2D: PFS in Cohorts 3 to 6
PFS is defined as the time from the date of first dose of study treatment to the date of first documentation of PD or date of death from any cause, whichever occurs first, regardless of the use of subsequent anti-cancer treatment. PD was defined in accordance with RECIST 1.1 criteria.
Phase 1b/2 RP2D: ORR in Cohorts 1 and 2
ORR is defined as the percentage of participants who have a best response to therapy of PR or CR in accordance with RECIST 1.1 criteria. CR: The disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Normalization of tumor marker level, if relevant. All lymph nodes must be non-pathological in size (< 10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Phase 1b/2 RP2D: Overall Survival (OS) in Cohorts 1 to 6
OS is defined as the time from the date of first dose of study treatment to the date of death from any cause. Subjects who were not known to have died at the data extraction will be censored at date last known alive.
Phase 1b/2 RP2D: Duration of Response (DOR) in Cohorts 1 to 6
DOR is defined for confirmed responders (PR or better) as time from the date of initial response (PR or better) to the date of first documentation of PD (according to RECIST 1.1) or death, whichever occurs first, regardless of use of subsequent anti-cancer treatment. Confirmed responders without documentation of PD or death or with unknown status at the data extraction were censored at the last adequate post-baseline disease assessment showing no evidence of PD. PD was defined as at least a 20% increase in the size of target lesions with an absolute increase of at least 5 mm, unequivocal progression of existing non-target lesions, or the appearance of one or more new lesions. Per protocol, participants in Phase 1b receiving the Phase 2 RP2D and participants in Phase 2 RP2D were analyzed together.
Phase 1b: Observed Maximum Concentration (Cmax) for Ibrutinib and Its Metabolite PCI-45227 in Cohorts 1 to 4
Actual collection times relative to ibrutinib administration were used for the calculation of pharmacokinetic parameters of ibrutinib and PCI-45227. For actual predose collection times that were < 0, these values were set equal to 0. Predose concentrations were applied as 24 hour concentrations in order to calculate steady-state (Cycle 2 Day 1) pharmacokinetic parameters for ibrutinib and PCI-45227. The Cmax was noted as observed.
Phase 1b: Time to Cmax (Tmax) for Ibrutinib and Its Metabolite PCI-45227 in Cohorts 1 to 4
Actual collection times relative to ibrutinib administration were used for the calculation of pharmacokinetic parameters of ibrutinib and PCI-45227. For actual predose collection times that were < 0, these values were set equal to 0. Predose concentrations were applied as 24 hour concentrations in order to calculate steady-state (Cycle 2 Day 1) pharmacokinetic parameters for ibrutinib and PCI-45227. The tmax was noted as observed.
Phase 1b: Time of Last Observed Concentration (Tlast) for Ibrutinib and Its Metabolite PCI-45227 in Cohorts 1 to 4
Actual collection times relative to ibrutinib administration were used for the calculation of pharmacokinetic parameters of ibrutinib and PCI-45227. For actual predose collection times that were < 0, these values were set equal to 0. Predose concentrations were applied as 24 hour concentrations in order to calculate steady-state (Cycle 2 Day 1) pharmacokinetic parameters for ibrutinib and PCI-45227. The tlast was noted as observed.
Phase 1b: Area Under the Concentration-Time Curve From Time 0 to Hour 24 (AUC0-24h) for Ibrutinib and Its Metabolite PCI-45227 in Cohorts 1 to 4
Actual collection times relative to ibrutinib administration were used for the calculation of pharmacokinetic parameters of ibrutinib and PCI-45227. For actual predose collection times that were < 0, these values were set equal to 0. Predose concentrations were applied as 24 hour concentrations in order to calculate steady-state (Cycle 2 Day 1) pharmacokinetic parameters for ibrutinib and PCI-45227. The AUC0-24h was calculated by the linear trapezoidal method.
Phase 1b: Area Under the Concentration-Time Curve to Last Observed Time Point (AUClast) for Ibrutinib and Its Metabolite PCI-45227 in Cohorts 1 to 4
Actual collection times relative to ibrutinib administration were used for the calculation of pharmacokinetic parameters of ibrutinib and PCI-45227. For actual predose collection times that were < 0, these values were set equal to 0. Predose concentrations were applied as 24 hour concentrations in order to calculate steady-state (Cycle 2 Day 1) pharmacokinetic parameters for ibrutinib and PCI-45227. The AUClast was calculated by the linear trapezoidal method.
Phase 1b: Terminal Elimination Half-Life (t1/2term) for Ibrutinib and Its Metabolite PCI-45227 in Cohorts 1 to 4
Actual collection times relative to ibrutinib administration were used for the calculation of pharmacokinetic parameters of ibrutinib and PCI-45227. For actual predose collection times that were < 0, these values were set equal to 0. Predose concentrations were applied as 24 hour concentrations in order to calculate steady-state (Cycle 2 Day 1) pharmacokinetic parameters for ibrutinib and PCI-45227. The apparent t1/2term was calculated by ln(2)/λz, where λz is the apparent elimination rate constant obtained by linear regression of three or more log-transformed data points in the terminal phase (not including Cmax).
Phase 1b: Terminal Elimination Rate Constant (λz) for Ibrutinib and Its Metabolite PCI-45227 in Cohorts 1 to 4
Actual collection times relative to ibrutinib administration were used for the calculation of pharmacokinetic parameters of ibrutinib and PCI-45227. For actual predose collection times that were < 0, these values were set equal to 0. Predose concentrations were applied as 24 hour concentrations in order to calculate steady-state (Cycle 2 Day 1) pharmacokinetic parameters for ibrutinib and PCI-45227. The λz is the apparent elimination rate constant obtained by linear regression of three or more log-transformed data points in the terminal phase (not including Cmax).
Phase 1b: Apparent Total Clearance at Steady-State (CLss/F) for Ibrutinib in Cohorts 1 to 4
Actual collection times relative to ibrutinib administration were used for the calculation of pharmacokinetic parameters of ibrutinib and PCI-45227. For actual predose collection times that were < 0, these values were set equal to 0. Predose concentrations were applied as 24 hour concentrations in order to calculate steady-state (Cycle 2 Day 1) pharmacokinetic parameters for ibrutinib and PCI-45227. Apparent total CLss/F (Cycle 2 Day 1) was calculated as dose/AUC0-24h.

Full Information

First Posted
November 4, 2015
Last Updated
September 27, 2022
Sponsor
Pharmacyclics LLC.
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1. Study Identification

Unique Protocol Identification Number
NCT02599324
Brief Title
Study to Evaluate Ibrutinib Combination Therapy in Patients With Selected Gastrointestinal and Genitourinary Tumors
Official Title
A Phase 1b/2 Study of Ibrutinib Combination Therapy in Selected Advanced Gastrointestinal and Genitourinary Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Completed
Study Start Date
December 1, 2015 (Actual)
Primary Completion Date
August 20, 2021 (Actual)
Study Completion Date
August 20, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pharmacyclics LLC.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to evaluate the safety, tolerability, and efficacy of single agent ibrutinib or the combination treatments of ibrutinib with everolimus, paclitaxel, docetaxel, pembrolizumab or cetuximab in selected advance gastrointestinal and genitourinary tumors.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Renal Cell Carcinoma, Advanced Urothelial Carcinoma, Advanced Gastric Adenocarcinoma, Metastatic Colorectal Adenocarcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
263 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1: Renal Cell Carcinoma (RCC)
Arm Type
Experimental
Arm Description
Phase 1b: Participants receive ibrutinib at various dose levels in combination with a fixed dose of everolimus to determine the recommended phase 2 dose (RP2D) of ibrutinib. (The RP2D was determined for each cohort separately.) Phase 2: Participants receive ibrutinib at the RP2D determined in phase 1b in combination with everolimus.
Arm Title
Cohort 2: Urothelial Carcinoma (UC)
Arm Type
Experimental
Arm Description
Phase 1b: Participants receive ibrutinib at various dose levels in combination with a fixed dose of paclitaxel to determine the RP2D of ibrutinib. (The RP2D was determined for each cohort separately.) Phase 2: Participants receive ibrutinib at the RP2D determined in Phase 1b in combination with paclitaxel.
Arm Title
Cohort 3: Gastric Adenocarcinoma (GA or GC)
Arm Type
Experimental
Arm Description
Phase 1b: Participants receive ibrutinib at various dose levels in combination with a fixed dose of docetaxel to determine the RP2D of ibrutinib. (The RP2D was determined for each cohort separately.) Phase 2: Participants receive docetaxel at the RP2D determined in Phase 1b in combination with docetaxel.
Arm Title
Cohort 4: Colorectal Adenocarcinoma (CRC)
Arm Type
Experimental
Arm Description
Phase 1b: Participants receive ibrutinib at various dose levels in combination with a fixed dose of cetuximab to determine RP2D of ibrutinib. (The RP2D was determined for each cohort separately.) Phase 2: Participants receive ibrutinib at the RP2D determined in Phase 1b in combination with cetuximab.
Arm Title
Cohort 5: Urothelial Carcinoma (UC) Ibrutinib
Arm Type
Experimental
Arm Description
Phase 1b: Participants receive ibrutinib at various dose levels to determine the RP2D of ibrutinib.(The RP2D was determined for each cohort separately.) Phase 2: Participants receive ibrutinib at the RP2D determined in Phase 1b.
Arm Title
Cohort 6: Urothelial Carcinoma (UC) With Pembrolizumab
Arm Type
Experimental
Arm Description
Phase 1b: Participants receive ibrutinib at various dose levels in combination with a fixed dose of pembrolizumab to determine the RP2D of ibrutinib. (The RP2D was determined for each cohort separately.) Phase 2: Participants receive ibrutinib at the RP2D determined in Phase 1b in combination with pembrolizumab.
Intervention Type
Drug
Intervention Name(s)
ibrutinib
Intervention Description
Ibrutinib administered orally once daily with 8 ounces (approximately 240 mL) of water.
Intervention Type
Drug
Intervention Name(s)
everolimus
Intervention Description
Everolimus 10 mg tablets should be taken orally once daily at the same time every day, either consistently with food or consistently without food. Four (4) x 2.5 mg tablets or two (2) x 5.0 mg tablets may be substituted if 10 mg tablet strength is not available.
Intervention Type
Drug
Intervention Name(s)
paclitaxel
Intervention Description
Paclitaxel should be administered as a 60-minute (±10 minutes) infusion. Paclitaxel should be given at a dose level of 80 mg/m^2, once weekly, in continual 3 weekly cycles.
Intervention Type
Drug
Intervention Name(s)
docetaxel
Intervention Description
Docetaxel administered as a 60 minute infusion (±10 minutes) at a dose level of 60 - 75 mg/m^2 (according to local institutional standard of care), given continually in 21-day cycles.
Intervention Type
Drug
Intervention Name(s)
cetuximab
Intervention Description
Cetuximab 400 mg/m^2 administered as a 120-minute IV infusion. The recommended subsequent weekly dose (all other infusions) is 250 mg/m^2 infused over 60 minutes.
Intervention Type
Drug
Intervention Name(s)
pembrolizumab
Intervention Description
Pembrolizumab 200 mg intravenous (IV) every 3 weeks.
Primary Outcome Measure Information:
Title
Phase 1b: Number of Participants With Dose-Limiting Toxicities (DLTs) in Cohorts 1 to 6
Description
A DLT was defined as any Grade 3 (severe) or higher non-hematologic or Grade 4 (life-threatening) hematologic adverse event (AE) occurring during the DLT observation period that was considered to be at least possibly related to the study treatment (ibrutinib or drug combination).
Time Frame
21 days after the initiation of therapy at the start of Cycle 1
Title
Phase 1b/2 RP2D: Progression-Free Survival (PFS) as Assessed by Investigator in Cohorts 1 and 2
Description
PFS is defined as the time from the date of first dose of study treatment to the date of first documentation of progressive disease (PD) or date of death from any cause, whichever occurs first, regardless of the use of subsequent anti-cancer treatment. PD was defined in accordance with Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study), and an absolute increase of ≥ 5 mm, or unequivocal progression of existing non-target lesions or the appearance of new lesions.
Time Frame
Maximum time on study for Cohort 1 (Phase 1b/2 RP2D) was 37.4 months; for Cohort 2 (Phase 1b/2 RP2D) was 44.7 months.
Title
Phase 1b/2 RP2D: Overall Response Rate (ORR) as Assessed by Investigator in Cohorts 3 to 6
Description
ORR is defined as the percentage of participants who have a best response of partial response (PR) or complete response (CR) to therapy in accordance with RECIST 1.1 criteria. CR: The disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Normalization of tumor marker level, if relevant. All lymph nodes must be non-pathological in size (< 10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time Frame
Maximum time on study (Phase 1b/2 RP2D) for Cohort 3 was 41.9 months; for Cohort 4 was 23.5 months; for Cohort 5 was 17.3 months; for Cohort 6 was 20.1 months.
Secondary Outcome Measure Information:
Title
Phase 1b: ORR in Cohorts 1 to 6
Description
ORR is defined as the percentage of participants who have a best response of partial response (PR) or complete response (CR) to therapy in accordance with RECIST 1.1 criteria. CR: The disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Normalization of tumor marker level, if relevant. All lymph nodes must be non-pathological in size (< 10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time Frame
Maximum time on study (Phase 1b only) for Cohort 1 was 37.4 months; for Cohort 2 was 44.7 months; for Cohort 3 was 41.9 months; for Cohort 4 was 34.2 months; for Cohort 5 was 17.3 months; for Cohort 6 was 20.1 months.
Title
Phase 1b: Disease Control Rate (DCR) in Cohorts 1 to 6
Description
DCR is is defined as the percentage of participants who have a best response of PR, CR, or stable disease (SD) to therapy in accordance with RECIST 1.1 criteria. CR: The disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Normalization of tumor marker level, if relevant. All lymph nodes must be non-pathological in size (< 10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD since the treatment started (baseline or after). For SD, tthere was no need for confirmation by a subsequent imaging assessment.
Time Frame
Maximum time on study (Phase 1b only) for Cohort 1 was 37.4 months; for Cohort 2 was 44.7 months; for Cohort 3 was 41.9 months; for Cohort 4 was 34.2 months; for Cohort 5 was 17.3 months; for Cohort 6 was 20.1 months.
Title
Phase 1b/2 RP2D: DCR in Cohorts 1 to 6
Description
DCR is is defined as the percentage of participants who have a best response of PR, CR, or SD to therapy in accordance with RECIST 1.1 criteria. CR: The disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Normalization of tumor marker level, if relevant. All lymph nodes must be non-pathological in size (< 10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD since the treatment started (baseline or after). For SD, tthere was no need for confirmation by a subsequent imaging assessment.
Time Frame
Maximum time on study (Phase 1b/2 RP2D) for Cohort 1 was 37.4 months; for Cohort 2 was 44.7 months; for Cohort 3 was 41.9 months; for Cohort 4 was 23.5 months; for Cohort 5 was 17.3 months; for Cohort 6 was 20.1 months. (Reverse Kaplan-Meier estimates)
Title
Phase 1b/2 RP2D: PFS in Cohorts 3 to 6
Description
PFS is defined as the time from the date of first dose of study treatment to the date of first documentation of PD or date of death from any cause, whichever occurs first, regardless of the use of subsequent anti-cancer treatment. PD was defined in accordance with RECIST 1.1 criteria.
Time Frame
Maximum time on study (Phase 1b/2 RP2D) for Cohort 3 was 41.9 months; for Cohort 4 was 23.5 months; for Cohort 5 was 17.3 months; for Cohort 6 was 20.1 months. (Reverse Kaplan-Meier estimates)
Title
Phase 1b/2 RP2D: ORR in Cohorts 1 and 2
Description
ORR is defined as the percentage of participants who have a best response to therapy of PR or CR in accordance with RECIST 1.1 criteria. CR: The disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Normalization of tumor marker level, if relevant. All lymph nodes must be non-pathological in size (< 10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time Frame
Maximum time on study for Cohort 1 (Phase 1b/2 RP2D) was 37.4 months; for Cohort 2 (Phase 1b/2 RP2D) was 44.7 months. (Reverse Kaplan-Meier estimates)
Title
Phase 1b/2 RP2D: Overall Survival (OS) in Cohorts 1 to 6
Description
OS is defined as the time from the date of first dose of study treatment to the date of death from any cause. Subjects who were not known to have died at the data extraction will be censored at date last known alive.
Time Frame
Maximum time on study (Phase 1b/2 RP2D) for Cohort 1 was 37.4 months; for Cohort 2 was 44.7 months; for Cohort 3 was 41.9 months; for Cohort 4 was 23.5 months; for Cohort 5 was 17.3 months; for Cohort 6 was 20.1 months. (Reverse Kaplan-Meier estimates)
Title
Phase 1b/2 RP2D: Duration of Response (DOR) in Cohorts 1 to 6
Description
DOR is defined for confirmed responders (PR or better) as time from the date of initial response (PR or better) to the date of first documentation of PD (according to RECIST 1.1) or death, whichever occurs first, regardless of use of subsequent anti-cancer treatment. Confirmed responders without documentation of PD or death or with unknown status at the data extraction were censored at the last adequate post-baseline disease assessment showing no evidence of PD. PD was defined as at least a 20% increase in the size of target lesions with an absolute increase of at least 5 mm, unequivocal progression of existing non-target lesions, or the appearance of one or more new lesions. Per protocol, participants in Phase 1b receiving the Phase 2 RP2D and participants in Phase 2 RP2D were analyzed together.
Time Frame
Maximum time on study (Phase 1b/2 RP2D) for Cohort 1 was 37.4 months; for Cohort 2 was 44.7 months; for Cohort 3 was 41.9 months; for Cohort 4 was 23.5 months; for Cohort 5 was 17.3 months; for Cohort 6 was 20.1 months. (Reverse Kaplan-Meier estimates)
Title
Phase 1b: Observed Maximum Concentration (Cmax) for Ibrutinib and Its Metabolite PCI-45227 in Cohorts 1 to 4
Description
Actual collection times relative to ibrutinib administration were used for the calculation of pharmacokinetic parameters of ibrutinib and PCI-45227. For actual predose collection times that were < 0, these values were set equal to 0. Predose concentrations were applied as 24 hour concentrations in order to calculate steady-state (Cycle 2 Day 1) pharmacokinetic parameters for ibrutinib and PCI-45227. The Cmax was noted as observed.
Time Frame
Cycle 2 Day 1: predose, 1 h ± 15 min, 2 h ± 15 min, 4 h ± 15 min, 6 h ± 15 min postdose
Title
Phase 1b: Time to Cmax (Tmax) for Ibrutinib and Its Metabolite PCI-45227 in Cohorts 1 to 4
Description
Actual collection times relative to ibrutinib administration were used for the calculation of pharmacokinetic parameters of ibrutinib and PCI-45227. For actual predose collection times that were < 0, these values were set equal to 0. Predose concentrations were applied as 24 hour concentrations in order to calculate steady-state (Cycle 2 Day 1) pharmacokinetic parameters for ibrutinib and PCI-45227. The tmax was noted as observed.
Time Frame
Cycle 2 Day 1: predose, 1 h ± 15 min, 2 h ± 15 min, 4 h ± 15 min, 6 h ± 15 min postdose
Title
Phase 1b: Time of Last Observed Concentration (Tlast) for Ibrutinib and Its Metabolite PCI-45227 in Cohorts 1 to 4
Description
Actual collection times relative to ibrutinib administration were used for the calculation of pharmacokinetic parameters of ibrutinib and PCI-45227. For actual predose collection times that were < 0, these values were set equal to 0. Predose concentrations were applied as 24 hour concentrations in order to calculate steady-state (Cycle 2 Day 1) pharmacokinetic parameters for ibrutinib and PCI-45227. The tlast was noted as observed.
Time Frame
Cycle 2 Day 1: predose, 1 h ± 15 min, 2 h ± 15 min, 4 h ± 15 min, 6 h ± 15 min postdose
Title
Phase 1b: Area Under the Concentration-Time Curve From Time 0 to Hour 24 (AUC0-24h) for Ibrutinib and Its Metabolite PCI-45227 in Cohorts 1 to 4
Description
Actual collection times relative to ibrutinib administration were used for the calculation of pharmacokinetic parameters of ibrutinib and PCI-45227. For actual predose collection times that were < 0, these values were set equal to 0. Predose concentrations were applied as 24 hour concentrations in order to calculate steady-state (Cycle 2 Day 1) pharmacokinetic parameters for ibrutinib and PCI-45227. The AUC0-24h was calculated by the linear trapezoidal method.
Time Frame
Cycle 2 Day 1: predose, 1 h ± 15 min, 2 h ± 15 min, 4 h ± 15 min, 6 h ± 15 min postdose
Title
Phase 1b: Area Under the Concentration-Time Curve to Last Observed Time Point (AUClast) for Ibrutinib and Its Metabolite PCI-45227 in Cohorts 1 to 4
Description
Actual collection times relative to ibrutinib administration were used for the calculation of pharmacokinetic parameters of ibrutinib and PCI-45227. For actual predose collection times that were < 0, these values were set equal to 0. Predose concentrations were applied as 24 hour concentrations in order to calculate steady-state (Cycle 2 Day 1) pharmacokinetic parameters for ibrutinib and PCI-45227. The AUClast was calculated by the linear trapezoidal method.
Time Frame
Cycle 2 Day 1: predose, 1 h ± 15 min, 2 h ± 15 min, 4 h ± 15 min, 6 h ± 15 min postdose
Title
Phase 1b: Terminal Elimination Half-Life (t1/2term) for Ibrutinib and Its Metabolite PCI-45227 in Cohorts 1 to 4
Description
Actual collection times relative to ibrutinib administration were used for the calculation of pharmacokinetic parameters of ibrutinib and PCI-45227. For actual predose collection times that were < 0, these values were set equal to 0. Predose concentrations were applied as 24 hour concentrations in order to calculate steady-state (Cycle 2 Day 1) pharmacokinetic parameters for ibrutinib and PCI-45227. The apparent t1/2term was calculated by ln(2)/λz, where λz is the apparent elimination rate constant obtained by linear regression of three or more log-transformed data points in the terminal phase (not including Cmax).
Time Frame
Cycle 2 Day 1: predose, 1 h ± 15 min, 2 h ± 15 min, 4 h ± 15 min, 6 h ± 15 min postdose
Title
Phase 1b: Terminal Elimination Rate Constant (λz) for Ibrutinib and Its Metabolite PCI-45227 in Cohorts 1 to 4
Description
Actual collection times relative to ibrutinib administration were used for the calculation of pharmacokinetic parameters of ibrutinib and PCI-45227. For actual predose collection times that were < 0, these values were set equal to 0. Predose concentrations were applied as 24 hour concentrations in order to calculate steady-state (Cycle 2 Day 1) pharmacokinetic parameters for ibrutinib and PCI-45227. The λz is the apparent elimination rate constant obtained by linear regression of three or more log-transformed data points in the terminal phase (not including Cmax).
Time Frame
Cycle 2 Day 1: predose, 1 h ± 15 min, 2 h ± 15 min, 4 h ± 15 min, 6 h ± 15 min postdose
Title
Phase 1b: Apparent Total Clearance at Steady-State (CLss/F) for Ibrutinib in Cohorts 1 to 4
Description
Actual collection times relative to ibrutinib administration were used for the calculation of pharmacokinetic parameters of ibrutinib and PCI-45227. For actual predose collection times that were < 0, these values were set equal to 0. Predose concentrations were applied as 24 hour concentrations in order to calculate steady-state (Cycle 2 Day 1) pharmacokinetic parameters for ibrutinib and PCI-45227. Apparent total CLss/F (Cycle 2 Day 1) was calculated as dose/AUC0-24h.
Time Frame
Cycle 2 Day 1: predose, 1 h ± 15 min, 2 h ± 15 min, 4 h ± 15 min, 6 h ± 15 min postdose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pharmacyclics LLC
Organizational Affiliation
Pharmacyclics LLC.
Official's Role
Study Director
Facility Information:
Facility Name
Clearview Cancer Institute /ID# 1128-0965
City
Huntsville
State/Province
Alabama
ZIP/Postal Code
35805
Country
United States
Facility Name
Banner MD Anderson Cancer Center /ID# 1128-0802
City
Gilbert
State/Province
Arizona
ZIP/Postal Code
85234
Country
United States
Facility Name
University of Arizona Cancer Center - Tucson /ID# 1128-1546
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Facility Name
Alta Bates Comprehensive Cancer Center /ID# 1128-0135
City
Berkeley
State/Province
California
ZIP/Postal Code
94704
Country
United States
Facility Name
St Marys Medical Center /ID# 1128-0969
City
Daly City
State/Province
California
ZIP/Postal Code
94015
Country
United States
Facility Name
Duplicate_University of California San Diego/ Moores Cancer Center /ID# 1128-0241
City
La Jolla
State/Province
California
ZIP/Postal Code
92037-0845
Country
United States
Facility Name
VA Long Beach Healthcare System /ID# 1128-0480
City
Long Beach
State/Province
California
ZIP/Postal Code
90822-5201
Country
United States
Facility Name
USC Norris Cancer Center /ID# 1128-0209
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
UC Irvine Medical Center - Chao Family Comprehensive Cancer Center /ID# 1128-0008
City
Orange
State/Province
California
ZIP/Postal Code
92868-3201
Country
United States
Facility Name
Gregory Smith, MD (Private Practice) /ID# 1128-0419
City
Saint Helena
State/Province
California
ZIP/Postal Code
94574
Country
United States
Facility Name
Salinas Valley Memorial Hosp /ID# 1128-0482
City
Salinas
State/Province
California
ZIP/Postal Code
93901
Country
United States
Facility Name
Premiere Oncology, A Medical Corporation /ID# 1128-1085
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
St. Joseph Health /ID# 1128-1462
City
Santa Rosa
State/Province
California
ZIP/Postal Code
95403
Country
United States
Facility Name
Whittingham Cancer Center at Norwalk Hospital /ID# 1128-0411
City
Norwalk
State/Province
Connecticut
ZIP/Postal Code
06856-3852
Country
United States
Facility Name
Georgetown University Hospital /ID# 1128-0824
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
Duplicate_Cancer Specialist of North Florida (CSNF) ( R ) /ID# 1128-1093
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32207
Country
United States
Facility Name
IACT Health-Columbus /ID# 1128-1389
City
Columbus
State/Province
Georgia
ZIP/Postal Code
31904-8946
Country
United States
Facility Name
Northshore Kellogg Cancer Center /ID# 1128-0484
City
Evanston
State/Province
Illinois
ZIP/Postal Code
60201
Country
United States
Facility Name
Franciscan Health Indianapolis /ID# 1128-1125
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46237
Country
United States
Facility Name
Horizon Oncology Research Center /ID# 1128-0337
City
Lafayette
State/Province
Indiana
ZIP/Postal Code
47905
Country
United States
Facility Name
University of Iowa Hospitals and Clinics /ID# 1128-0766
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
The University of Kansas Cancer Center /ID# 1128-0706
City
Fairway
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
Facility Name
East Jefferson General Hospital /ID# 1128-1084
City
Metairie
State/Province
Louisiana
ZIP/Postal Code
70006
Country
United States
Facility Name
Duplicate_Tufts Medical Center /ID# 1128-0016
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111-1552
Country
United States
Facility Name
Barbara Ann Karmanos Cancer In /ID# 1128-0130
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Henry Ford Hospital /ID# 1128-0195
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Central Care Cancer Center /ID# 1128-1596
City
Bolivar
State/Province
Missouri
ZIP/Postal Code
65613
Country
United States
Facility Name
Capital Region Medical Center /ID# 1128-1412
City
Jefferson City
State/Province
Missouri
ZIP/Postal Code
65102
Country
United States
Facility Name
Nebraska Methodist Hospital /ID# 1128-0229
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68114
Country
United States
Facility Name
New Jersey Center for Cancer Research /ID# 1128-0493
City
Brick
State/Province
New Jersey
ZIP/Postal Code
08724
Country
United States
Facility Name
Duplicate_New Mexico Cancer Care Alliance /ID# 1128-0938
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87106
Country
United States
Facility Name
San Juan Oncology Associates /ID# 1128-1020
City
Farmington
State/Province
New Mexico
ZIP/Postal Code
87401
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center-Koch Center /ID# 1128-0091
City
New York
State/Province
New York
ZIP/Postal Code
10065-6007
Country
United States
Facility Name
Wake Forest Univ HS /ID# 1128-0975
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
Oregon Health & Science University /ID# 1128-0251
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239-3011
Country
United States
Facility Name
Penn State Hershey Medical Ctr /ID# 1128-0220
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033-2360
Country
United States
Facility Name
Abramson Cancer Center of the Univ. of Pennsylvania /ID# 1128-0402
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Vanderbilt Infectious Disease Clinic /ID# 1128-0024
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
The University of Texas Medical Branch (UTMB) - Cancer Center - Galves /ID# 1128-0974
City
Galveston
State/Province
Texas
ZIP/Postal Code
77555-0565
Country
United States
Facility Name
Duplicate_Scott & White Mem Hosp & Clin /ID# 1128-0046
City
Temple
State/Province
Texas
ZIP/Postal Code
76508
Country
United States
Facility Name
Duplicate_Virginia Cancer Specialists - Fairfax Office /ID# 1128-0972
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Facility Name
Virginia Mason Medical Center /ID# 1128-0005
City
Seattle
State/Province
Washington
ZIP/Postal Code
98101
Country
United States
Facility Name
University of Washington /ID# 1128-1382
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
Confluence Health /ID# 1128-0894
City
Wenatchee
State/Province
Washington
ZIP/Postal Code
98801
Country
United States
Facility Name
Seoul National University Bundang Hospital /ID# 1128-0982
City
Seongnam
State/Province
Gyeonggido
ZIP/Postal Code
13620
Country
Korea, Republic of
Facility Name
Yonsei University Health System Severance Hospital /ID# 1128-0927
City
Seoul
State/Province
Seoul Teugbyeolsi
ZIP/Postal Code
03722
Country
Korea, Republic of
Facility Name
Chonnam National University Hwasun Hospital /ID# 1128-0916
City
Jeonnam
ZIP/Postal Code
58128
Country
Korea, Republic of
Facility Name
Seoul National University Hospital /ID# 1128-0926
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Asan Medical Center /ID# 1128-0963
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Samsung Medical Center /ID# 1128-0925
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
The Catholic University of Korea, Seoul St. Mary's Hospital /ID# 1128-0928
City
Seoul
ZIP/Postal Code
06591
Country
Korea, Republic of
Facility Name
Korea University Guro Hospital /ID# 1128-0924
City
Seoul
ZIP/Postal Code
08308
Country
Korea, Republic of
Facility Name
Instituto Catalan de Oncologia (ICO) Badalona /ID# 1128-0984
City
Badalona
State/Province
Barcelona
ZIP/Postal Code
08916
Country
Spain
Facility Name
Hospital Unversitario Marques de Valdecilla /ID# 1128-0973
City
Santander
State/Province
Cantabria
ZIP/Postal Code
39008
Country
Spain
Facility Name
Hospital Universitario Vall d'Hebron /ID# 1128-0534
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Clinic de Barcelona /ID# 1128-0533
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Hospital Universitario Ramon y Cajal /ID# 1128-0874
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Hospital Universitario 12 de Octubre /ID# 1128-0864
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Hospital Universitario La Paz /ID# 1128-0921
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Hospital Universitario Virgen del Rocio /ID# 1128-0863
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Facility Name
Sarah Cannon Research Institute /ID# 1128-1079
City
London
State/Province
England
ZIP/Postal Code
W1G 6AD
Country
United Kingdom
Facility Name
Duplicate_Beatson west of scotland cancer center /ID# 1128-0652
City
Glasgow
State/Province
Scotland
ZIP/Postal Code
G12 0YN
Country
United Kingdom
Facility Name
The Royal Marsden NHS Foundation Trust /ID# 1128-0543
City
London
ZIP/Postal Code
SW3 6JJ
Country
United Kingdom
Facility Name
The Christie Hospital /ID# 1128-0030
City
Manchester
ZIP/Postal Code
M20 4BX
Country
United Kingdom
Facility Name
Duplicate_Oxford University Hospitals NHS Trust /ID# 1128-0814
City
Oxford
ZIP/Postal Code
OX3 7LE
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Requests for access to individual participant data from clinical studies conducted by Pharmacyclics LLC, an AbbVie Company, can be submitted through Yale Open Data Access (YODA) Project site at the following link.
IPD Sharing URL
http://yoda.yale.edu

Learn more about this trial

Study to Evaluate Ibrutinib Combination Therapy in Patients With Selected Gastrointestinal and Genitourinary Tumors

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