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

November 14, 2023 updated by: Pharmacyclics LLC.

A Phase 1b/2 Study of Ibrutinib Combination Therapy in Selected Advanced Gastrointestinal and Genitourinary Tumors

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
263

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Korea, Republic of
      • Jeonnam, Korea, Republic of, 58128
        • Chonnam National University Hwasun Hospital /ID# 1128-0916
      • Seoul, Korea, Republic of, 03080
        • Seoul National University Hospital /ID# 1128-0926
      • Seoul, Korea, Republic of, 05505
        • Asan Medical Center /ID# 1128-0963
      • Seoul, Korea, Republic of, 06351
        • Samsung Medical Center /ID# 1128-0925
      • Seoul, Korea, Republic of, 06591
        • The Catholic University of Korea, Seoul St. Mary's Hospital /ID# 1128-0928
      • Seoul, Korea, Republic of, 08308
        • Korea University Guro Hospital /ID# 1128-0924
    • Gyeonggido
      • Seongnam, Gyeonggido, Korea, Republic of, 13620
        • Seoul National University Bundang Hospital /ID# 1128-0982
    • Seoul Teugbyeolsi
      • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 03722
        • Yonsei University Health System Severance Hospital /ID# 1128-0927
  • Spain
      • Barcelona, Spain, 08035
        • Hospital Universitario Vall d'Hebron /ID# 1128-0534
      • Barcelona, Spain, 08036
        • Hospital Clinic de Barcelona /ID# 1128-0533
      • Madrid, Spain, 28034
        • Hospital Universitario Ramon y Cajal /ID# 1128-0874
      • Madrid, Spain, 28041
        • Hospital Universitario 12 de Octubre /ID# 1128-0864
      • Madrid, Spain, 28046
        • Hospital Universitario La Paz /ID# 1128-0921
      • Sevilla, Spain, 41013
        • Hospital Universitario Virgen del Rocio /ID# 1128-0863
    • Barcelona
      • Badalona, Barcelona, Spain, 08916
        • Instituto Catalan de Oncologia (ICO) Badalona /ID# 1128-0984
    • Cantabria
      • Santander, Cantabria, Spain, 39008
        • Hospital Unversitario Marques de Valdecilla /ID# 1128-0973
  • United Kingdom
      • London, United Kingdom, SW3 6JJ
        • The Royal Marsden NHS Foundation Trust /ID# 1128-0543
      • Manchester, United Kingdom, M20 4BX
        • The Christie Hospital /ID# 1128-0030
      • Oxford, United Kingdom, OX3 7LE
        • Duplicate_Oxford University Hospitals NHS Trust /ID# 1128-0814
    • England
      • London, England, United Kingdom, W1G 6AD
        • Sarah Cannon Research Institute /ID# 1128-1079
    • Scotland
      • Glasgow, Scotland, United Kingdom, G12 0YN
        • Duplicate_Beatson west of scotland cancer center /ID# 1128-0652
  • United States
    • Alabama
      • Huntsville, Alabama, United States, 35805
        • Clearview Cancer Institute /ID# 1128-0965
    • Arizona
      • Gilbert, Arizona, United States, 85234
        • Banner MD Anderson Cancer Center /ID# 1128-0802
      • Tucson, Arizona, United States, 85724
        • University of Arizona Cancer Center - Tucson /ID# 1128-1546
    • California
      • Berkeley, California, United States, 94704
        • Alta Bates Comprehensive Cancer Center /ID# 1128-0135
      • Daly City, California, United States, 94015
        • St Marys Medical Center /ID# 1128-0969
      • La Jolla, California, United States, 92037-0845
        • Duplicate_University of California San Diego/ Moores Cancer Center /ID# 1128-0241
      • Long Beach, California, United States, 90822-5201
        • VA Long Beach Healthcare System /ID# 1128-0480
      • Los Angeles, California, United States, 90033
        • USC Norris Cancer Center /ID# 1128-0209
      • Orange, California, United States, 92868-3201
        • UC Irvine Medical Center - Chao Family Comprehensive Cancer Center /ID# 1128-0008
      • Saint Helena, California, United States, 94574
        • Gregory Smith, MD (Private Practice) /ID# 1128-0419
      • Salinas, California, United States, 93901
        • Salinas Valley Memorial Hosp /ID# 1128-0482
      • Santa Monica, California, United States, 90404
        • Premiere Oncology, A Medical Corporation /ID# 1128-1085
      • Santa Rosa, California, United States, 95403
        • St. Joseph Health /ID# 1128-1462
    • Connecticut
      • Norwalk, Connecticut, United States, 06856-3852
        • Whittingham Cancer Center at Norwalk Hospital /ID# 1128-0411
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Georgetown University Hospital /ID# 1128-0824
    • Florida
      • Jacksonville, Florida, United States, 32207
        • Duplicate_Cancer Specialist of North Florida (CSNF) ( R ) /ID# 1128-1093
    • Georgia
      • Columbus, Georgia, United States, 31904-8946
        • IACT Health-Columbus /ID# 1128-1389
    • Illinois
      • Evanston, Illinois, United States, 60201
        • Northshore Kellogg Cancer Center /ID# 1128-0484
    • Indiana
      • Indianapolis, Indiana, United States, 46237
        • Franciscan Health Indianapolis /ID# 1128-1125
      • Lafayette, Indiana, United States, 47905
        • Horizon Oncology Research Center /ID# 1128-0337
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa Hospitals and Clinics /ID# 1128-0766
    • Kansas
      • Fairway, Kansas, United States, 66205
        • The University of Kansas Cancer Center /ID# 1128-0706
    • Louisiana
      • Metairie, Louisiana, United States, 70006
        • East Jefferson General Hospital /ID# 1128-1084
    • Massachusetts
      • Boston, Massachusetts, United States, 02111-1552
        • Duplicate_Tufts Medical Center /ID# 1128-0016
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Barbara Ann Karmanos Cancer In /ID# 1128-0130
      • Detroit, Michigan, United States, 48202
        • Henry Ford Hospital /ID# 1128-0195
    • Missouri
      • Bolivar, Missouri, United States, 65613
        • Central Care Cancer Center /ID# 1128-1596
      • Jefferson City, Missouri, United States, 65102
        • Capital Region Medical Center /ID# 1128-1412
    • Nebraska
      • Omaha, Nebraska, United States, 68114
        • Nebraska Methodist Hospital /ID# 1128-0229
    • New Jersey
      • Brick, New Jersey, United States, 08724
        • New Jersey Center for Cancer Research /ID# 1128-0493
    • New Mexico
      • Albuquerque, New Mexico, United States, 87106
        • Duplicate_New Mexico Cancer Care Alliance /ID# 1128-0938
      • Farmington, New Mexico, United States, 87401
        • San Juan Oncology Associates /ID# 1128-1020
    • New York
      • New York, New York, United States, 10065-6007
        • Memorial Sloan Kettering Cancer Center-Koch Center /ID# 1128-0091
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest Univ HS /ID# 1128-0975
    • Oregon
      • Portland, Oregon, United States, 97239-3011
        • Oregon Health & Science University /ID# 1128-0251
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033-2360
        • Penn State Hershey Medical Ctr /ID# 1128-0220
      • Philadelphia, Pennsylvania, United States, 19104
        • Abramson Cancer Center of the Univ. of Pennsylvania /ID# 1128-0402
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt Infectious Disease Clinic /ID# 1128-0024
    • Texas
      • Galveston, Texas, United States, 77555-0565
        • The University of Texas Medical Branch (UTMB) - Cancer Center - Galves /ID# 1128-0974
      • Temple, Texas, United States, 76508
        • Duplicate_Scott & White Mem Hosp & Clin /ID# 1128-0046
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Duplicate_Virginia Cancer Specialists - Fairfax Office /ID# 1128-0972
    • Washington
      • Seattle, Washington, United States, 98101
        • Virginia Mason Medical Center /ID# 1128-0005
      • Seattle, Washington, United States, 98109
        • University of Washington /ID# 1128-1382
      • Wenatchee, Washington, United States, 98801
        • Confluence Health /ID# 1128-0894

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

RCC (clear cell), urothelial carcinoma (UC) (transitional cell), gastric or gastro-esophageal junctional (GEJ) adenocarcinoma, or K-RAS or N-RAS wild-type EGFR expressing CRC For cohort 1 RCC: minimum of 1 and maximum of 4 prior regimens, one or more of which must have included a VEGF-TKI For UC cohort 2: minimum of 1 and maximum of 2 prior regimens, one of which must have included a platinum-based regimen For UC cohort 5: Minimum of 1 and maximum of 2 prior regimens, one of which must have included a checkpoint inhibitor.

For UC cohort 6:

Locally advanced or mUC who are not eligible for cisplatin chemo with a PDL-1 score (CPS) of ≥ 10 without prior treatment.

Locally advanced or mUC who have progressed on platinum chemo or within 12 months of neo- or adjuvant therapy with a platinum chemotherapy. A minimum of 1 and maximum of 2 prior therapies.

For cohort 3 gastric or GEJ adenocarcinoma: minimum of 1 and maximum of 3 prior regimens one of which must have included a fluoropyrimidine regimen For cohort 4 CRC: minimum of 2 and maximum of 4 prior regimens, which must have included both an irinotecan and an oxaliplatin based regimen unless unable to tolerate irinotecan chemotherapy

Laboratory:

Adequate hematologic function:

Absolute neutrophil count ≥1500 cells/mm3 (1.5 x 109/L) Platelet count >80,000 cells/mm3 (80 x 109/L) for cohort 1 (RCC) Platelet counts >100,000 cells/mm3 (100 x 109/L) for all UC cohorts Hemoglobin ≥8.0 g/dL. for cohort 1 (RCC),all UC cohorts, and cohort 3 (GC) Hemoglobin ≥9.0 g/dL for cohort 4 (CRC)

Adequate hepatic and renal function defined as:

Serum aspartate transaminase (AST) and/or alanine transaminase (ALT) ≤5.0 x upper limit of normal (ULN) if liver metastases, or ≤3 x ULN without liver metastases Alkaline phosphatase <3.0 x ULN or ≤5.0 x ULN if liver or bone metastases present Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin, such as hemolysis) with the exception of subjects in the GC cohort where docetaxel is administered, these subjects must have bilirubin within normal limits (WNL) Estimated Creatinine Clearance ≥30 mL/min (Cockcroft-Gault)

Exclusion Criteria

Prior treatment with:

Everolimus or temsirolimus (RCC cohort 1) Any taxane (UC cohort of ibrutinib + paclitaxel) (cohort 2) Checkpoint inhibitors (UC cohort 6) Any taxane (GC cohort 3) Cetuximab or panitumumab (CRC cohort 4)

For all Cohorts:

Concomitant use of warfarin or other Vitamin K antagonists History of stroke or intracranial hemorrhage within 6 months prior to enrollment Major surgery within 4 weeks of first dose of study drug Requires treatment with strong CYP3A inhibitors known bleeding disorders or hemophilia

UC cohort 6 only:

Subjects who have an active, known or suspected autoimmune disease. Evidence of clinically significant interstitial lung disease or active, noninfectious pneumonitis.

Non-steroid immunosuppressive medications within 14 days before the first dose of ibrutinib and pembrolizumab.

Subjects in whom prior anti PD-1 / anti-PD-L1 therapy was intolerable and required discontinuation of treatment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Cohort 1: Renal Cell Carcinoma (RCC)

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.
Drug: ibrutinib
Ibrutinib administered orally once daily with 8 ounces (approximately 240 mL) of water.
Drug: everolimus
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.
Experimental: Cohort 2: Urothelial Carcinoma (UC)

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.
Drug: ibrutinib
Ibrutinib administered orally once daily with 8 ounces (approximately 240 mL) of water.
Drug: paclitaxel
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.
Experimental: Cohort 3: Gastric Adenocarcinoma (GA or GC)

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.
Drug: ibrutinib
Ibrutinib administered orally once daily with 8 ounces (approximately 240 mL) of water.
Drug: docetaxel
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.
Experimental: Cohort 4: Colorectal Adenocarcinoma (CRC)

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.
Drug: ibrutinib
Ibrutinib administered orally once daily with 8 ounces (approximately 240 mL) of water.
Drug: cetuximab
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.
Experimental: Cohort 5: Urothelial Carcinoma (UC) Ibrutinib

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.
Drug: ibrutinib
Ibrutinib administered orally once daily with 8 ounces (approximately 240 mL) of water.
Experimental: Cohort 6: Urothelial Carcinoma (UC) With Pembrolizumab

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.
Drug: ibrutinib
Ibrutinib administered orally once daily with 8 ounces (approximately 240 mL) of water.
Drug: pembrolizumab
Pembrolizumab 200 mg intravenous (IV) every 3 weeks.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Phase 1b: Number of Participants With Dose-Limiting Toxicities (DLTs) in Cohorts 1 to 6
Time Frame: 21 days after the initiation of therapy at the start of Cycle 1
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).
21 days after the initiation of therapy at the start of Cycle 1
Phase 1b/2 RP2D: Progression-Free Survival (PFS) as Assessed by Investigator in Cohorts 1 and 2
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.
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.
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.
Phase 1b/2 RP2D: Overall Response Rate (ORR) as Assessed by Investigator in Cohorts 3 to 6
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.
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.
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 Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Phase 1b: ORR in Cohorts 1 to 6
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.
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.
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.
Phase 1b: Disease Control Rate (DCR) in Cohorts 1 to 6
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.
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.
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.
Phase 1b/2 RP2D: DCR in Cohorts 1 to 6
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)
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.
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)
Phase 1b/2 RP2D: PFS in Cohorts 3 to 6
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)
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.
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)
Phase 1b/2 RP2D: ORR in Cohorts 1 and 2
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)
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.
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)
Phase 1b/2 RP2D: Overall Survival (OS) in Cohorts 1 to 6
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)
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.
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)
Phase 1b/2 RP2D: Duration of Response (DOR) in Cohorts 1 to 6
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)

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.
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)
Phase 1b: Observed Maximum Concentration (Cmax) for Ibrutinib and Its Metabolite PCI-45227 in Cohorts 1 to 4
Time Frame: Cycle 2 Day 1: predose, 1 h ± 15 min, 2 h ± 15 min, 4 h ± 15 min, 6 h ± 15 min postdose
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.
Cycle 2 Day 1: predose, 1 h ± 15 min, 2 h ± 15 min, 4 h ± 15 min, 6 h ± 15 min postdose
Phase 1b: Time to Cmax (Tmax) for Ibrutinib and Its Metabolite PCI-45227 in Cohorts 1 to 4
Time Frame: Cycle 2 Day 1: predose, 1 h ± 15 min, 2 h ± 15 min, 4 h ± 15 min, 6 h ± 15 min postdose
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.
Cycle 2 Day 1: predose, 1 h ± 15 min, 2 h ± 15 min, 4 h ± 15 min, 6 h ± 15 min postdose
Phase 1b: Time of Last Observed Concentration (Tlast) for Ibrutinib and Its Metabolite PCI-45227 in Cohorts 1 to 4
Time Frame: Cycle 2 Day 1: predose, 1 h ± 15 min, 2 h ± 15 min, 4 h ± 15 min, 6 h ± 15 min postdose
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.
Cycle 2 Day 1: predose, 1 h ± 15 min, 2 h ± 15 min, 4 h ± 15 min, 6 h ± 15 min postdose
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
Time Frame: Cycle 2 Day 1: predose, 1 h ± 15 min, 2 h ± 15 min, 4 h ± 15 min, 6 h ± 15 min postdose
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.
Cycle 2 Day 1: predose, 1 h ± 15 min, 2 h ± 15 min, 4 h ± 15 min, 6 h ± 15 min postdose
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
Time Frame: Cycle 2 Day 1: predose, 1 h ± 15 min, 2 h ± 15 min, 4 h ± 15 min, 6 h ± 15 min postdose
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.
Cycle 2 Day 1: predose, 1 h ± 15 min, 2 h ± 15 min, 4 h ± 15 min, 6 h ± 15 min postdose
Phase 1b: Terminal Elimination Half-Life (t1/2term) for Ibrutinib and Its Metabolite PCI-45227 in Cohorts 1 to 4
Time Frame: Cycle 2 Day 1: predose, 1 h ± 15 min, 2 h ± 15 min, 4 h ± 15 min, 6 h ± 15 min postdose
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).
Cycle 2 Day 1: predose, 1 h ± 15 min, 2 h ± 15 min, 4 h ± 15 min, 6 h ± 15 min postdose
Phase 1b: Terminal Elimination Rate Constant (λz) for Ibrutinib and Its Metabolite PCI-45227 in Cohorts 1 to 4
Time Frame: Cycle 2 Day 1: predose, 1 h ± 15 min, 2 h ± 15 min, 4 h ± 15 min, 6 h ± 15 min postdose
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).
Cycle 2 Day 1: predose, 1 h ± 15 min, 2 h ± 15 min, 4 h ± 15 min, 6 h ± 15 min postdose
Phase 1b: Apparent Total Clearance at Steady-State (CLss/F) for Ibrutinib in Cohorts 1 to 4
Time Frame: Cycle 2 Day 1: predose, 1 h ± 15 min, 2 h ± 15 min, 4 h ± 15 min, 6 h ± 15 min postdose
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.
Cycle 2 Day 1: predose, 1 h ± 15 min, 2 h ± 15 min, 4 h ± 15 min, 6 h ± 15 min postdose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Pharmacyclics LLC.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Pharmacyclics LLC, Pharmacyclics LLC.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 20, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 20, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 4, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 4, 2015

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 6, 2015

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 17, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 14, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PCYC-1128-CA
  • 2015-003656-40 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD 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 Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • CSR

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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