Metastatic Renal Cell CarcinomaPhase 1/2NCT02599324
Study to Evaluate Ibrutinib Combination Therapy in Patients With Selected Gastrointestinal and Genitourinary Tumors
A Phase 1/2 study testing ibrutinib, everolimus and paclitaxel in people with Metastatic Renal Cell Carcinoma and Advanced Urothelial Carcinoma, run by Pharmacyclics LLC. at 65 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Renal Cell Carcinoma, Advanced Urothelial Carcinoma, Advanced Gastric Adenocarcinoma
- What is being tested?
- ibrutinib, everolimus and paclitaxel
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 263 participants
- Where
- 65 sitesin 4 countries
- Study dates
- 1 Dec 2015to 20 Aug 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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)
Who cannot join
- 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.
Trial locations and contacts
65 sites in 4 countries.
65 sites in 4 countries
United States44 sites
Duplicate_New Mexico Cancer Care Alliance /ID# 1128-0938
Albuquerque, New Mexico, 87106
Alta Bates Comprehensive Cancer Center /ID# 1128-0135
Berkeley, California, 94704
Central Care Cancer Center /ID# 1128-1596
Bolivar, Missouri, 65613
Duplicate_Tufts Medical Center /ID# 1128-0016
Boston, Massachusetts, 02111-1552
New Jersey Center for Cancer Research /ID# 1128-0493
Brick, New Jersey, 08724
IACT Health-Columbus /ID# 1128-1389
Columbus, Georgia, 31904-8946
St Marys Medical Center /ID# 1128-0969
Daly City, California, 94015
Barbara Ann Karmanos Cancer In /ID# 1128-0130
Detroit, Michigan, 48201
Henry Ford Hospital /ID# 1128-0195
Detroit, Michigan, 48202
Northshore Kellogg Cancer Center /ID# 1128-0484
Evanston, Illinois, 60201
Duplicate_Virginia Cancer Specialists - Fairfax Office /ID# 1128-0972
Fairfax, Virginia, 22031
The University of Kansas Cancer Center /ID# 1128-0706
Fairway, Kansas, 66205
San Juan Oncology Associates /ID# 1128-1020
Farmington, New Mexico, 87401
The University of Texas Medical Branch (UTMB) - Cancer Center - Galves /ID# 1128-0974
Galveston, Texas, 77555-0565
Banner MD Anderson Cancer Center /ID# 1128-0802
Gilbert, Arizona, 85234
Penn State Hershey Medical Ctr /ID# 1128-0220
Hershey, Pennsylvania, 17033-2360
Clearview Cancer Institute /ID# 1128-0965
Huntsville, Alabama, 35805
Franciscan Health Indianapolis /ID# 1128-1125
Indianapolis, Indiana, 46237
University of Iowa Hospitals and Clinics /ID# 1128-0766
Iowa City, Iowa, 52242
Duplicate_Cancer Specialist of North Florida (CSNF) ( R ) /ID# 1128-1093
Jacksonville, Florida, 32207
Capital Region Medical Center /ID# 1128-1412
Jefferson City, Missouri, 65102
Duplicate_University of California San Diego/ Moores Cancer Center /ID# 1128-0241
La Jolla, California, 92037-0845
Horizon Oncology Research Center /ID# 1128-0337
Lafayette, Indiana, 47905
VA Long Beach Healthcare System /ID# 1128-0480
Long Beach, California, 90822-5201
USC Norris Cancer Center /ID# 1128-0209
Los Angeles, California, 90033
East Jefferson General Hospital /ID# 1128-1084
Metairie, Louisiana, 70006
Vanderbilt Infectious Disease Clinic /ID# 1128-0024
Nashville, Tennessee, 37232
Memorial Sloan Kettering Cancer Center-Koch Center /ID# 1128-0091
New York, New York, 10065-6007
Whittingham Cancer Center at Norwalk Hospital /ID# 1128-0411
Norwalk, Connecticut, 06856-3852
Nebraska Methodist Hospital /ID# 1128-0229
Omaha, Nebraska, 68114
UC Irvine Medical Center - Chao Family Comprehensive Cancer Center /ID# 1128-0008
Orange, California, 92868-3201
Abramson Cancer Center of the Univ. of Pennsylvania /ID# 1128-0402
Philadelphia, Pennsylvania, 19104
Oregon Health & Science University /ID# 1128-0251
Portland, Oregon, 97239-3011
Salinas Valley Memorial Hosp /ID# 1128-0482
Salinas, California, 93901
Premiere Oncology, A Medical Corporation /ID# 1128-1085
Santa Monica, California, 90404
St. Joseph Health /ID# 1128-1462
Santa Rosa, California, 95403
Virginia Mason Medical Center /ID# 1128-0005
Seattle, Washington, 98101
University of Washington /ID# 1128-1382
Seattle, Washington, 98109
Gregory Smith, MD (Private Practice) /ID# 1128-0419
St. Helena, California, 94574
Duplicate_Scott & White Mem Hosp & Clin /ID# 1128-0046
Temple, Texas, 76508
University of Arizona Cancer Center - Tucson /ID# 1128-1546
Tucson, Arizona, 85724
Georgetown University Hospital /ID# 1128-0824
Washington D.C., District of Columbia, 20007
Confluence Health /ID# 1128-0894
Wenatchee, Washington, 98801
Wake Forest Univ HS /ID# 1128-0975
Winston-Salem, North Carolina, 27157
South Korea8 sites
Chonnam National University Hwasun Hospital /ID# 1128-0916
Jeonnam, 58128
Seoul National University Bundang Hospital /ID# 1128-0982
Seongnam, Gyeonggido, 13620
Yonsei University Health System Severance Hospital /ID# 1128-0927
Seoul, Seoul Teugbyeolsi, 03722
Seoul National University Hospital /ID# 1128-0926
Seoul, 03080
Asan Medical Center /ID# 1128-0963
Seoul, 05505
Samsung Medical Center /ID# 1128-0925
Seoul, 06351
The Catholic University of Korea, Seoul St. Mary's Hospital /ID# 1128-0928
Seoul, 06591
Korea University Guro Hospital /ID# 1128-0924
Seoul, 08308
Spain8 sites
Instituto Catalan de Oncologia (ICO) Badalona /ID# 1128-0984
Badalona, Barcelona, 08916
Hospital Universitario Vall d'Hebron /ID# 1128-0534
Barcelona, 08035
Hospital Clinic de Barcelona /ID# 1128-0533
Barcelona, 08036
Hospital Universitario Ramon y Cajal /ID# 1128-0874
Madrid, 28034
Hospital Universitario 12 de Octubre /ID# 1128-0864
Madrid, 28041
Hospital Universitario La Paz /ID# 1128-0921
Madrid, 28046
Hospital Unversitario Marques de Valdecilla /ID# 1128-0973
Santander, Cantabria, 39008
Hospital Universitario Virgen del Rocio /ID# 1128-0863
Seville, 41013
United Kingdom5 sites
Duplicate_Beatson west of scotland cancer center /ID# 1128-0652
Glasgow, Scotland, G12 0YN
Sarah Cannon Research Institute /ID# 1128-1079
London, England, W1G 6AD
The Royal Marsden NHS Foundation Trust /ID# 1128-0543
London, SW3 6JJ
The Christie Hospital /ID# 1128-0030
Manchester, M20 4BX
Duplicate_Oxford University Hospitals NHS Trust /ID# 1128-0814
Oxford, OX3 7LE
About this study
Official title: 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.
- Conditions
- Metastatic Renal Cell Carcinoma, Advanced Urothelial Carcinoma, Advanced Gastric Adenocarcinoma, Metastatic Colorectal Adenocarcinoma
- Being tested
- ibrutinib, everolimus, paclitaxel, docetaxel, cetuximab
- Medical subject headings
- Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ibrutinibDrug
Ibrutinib administered orally once daily with 8 ounces (approximately 240 mL) of water.
everolimusDrug
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.
paclitaxelDrug
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.
docetaxelDrug
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.
cetuximabDrug
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.
pembrolizumabDrug
Pembrolizumab 200 mg intravenous (IV) every 3 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: Renal Cell Carcinoma (RCC) | Experimental | 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. Receives: Drug: ibrutinib; Drug: everolimus |
| Cohort 2: Urothelial Carcinoma (UC) | Experimental | 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. Receives: Drug: ibrutinib; Drug: paclitaxel |
| Cohort 3: Gastric Adenocarcinoma (GA or GC) | Experimental | 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. Receives: Drug: ibrutinib; Drug: docetaxel |
| Cohort 4: Colorectal Adenocarcinoma (CRC) | Experimental | 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. Receives: Drug: ibrutinib; Drug: cetuximab |
| Cohort 5: Urothelial Carcinoma (UC) Ibrutinib | Experimental | 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. Receives: Drug: ibrutinib |
| Cohort 6: Urothelial Carcinoma (UC) With Pembrolizumab | Experimental | 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. Receives: Drug: ibrutinib; Drug: pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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
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.
Measured: 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
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.
Measured: 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 outcomes (15)
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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).
Measured: 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
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).
Measured: 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
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.
Measured: Cycle 2 Day 1: predose, 1 h ± 15 min, 2 h ± 15 min, 4 h ± 15 min, 6 h ± 15 min postdose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2015 (estimated)
- Study start1 Dec 2015
- Primary completion20 Aug 2021
- Study completion20 Aug 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Renal Cell CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 263 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pharmacyclics LLC.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pharmacyclics LLC, Study director, Pharmacyclics LLC.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02599324
- Sponsor's protocol ID
- PCYC-1128-CA
- Other IDs
- 2015-003656-40, 2015
- Status last verified
- Sep 2022
- First submitted
- 4 Nov 2015
- Last updated
- 18 Nov 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Oh DY, Maqueda MA, Quinn DI, O'Dwyer PJ, Chau I, Kim SY, Duran I, Castellano D, Berlin J, Mellado B, Williamson SK, Lee KW, Marti F, Mathew P, Saif MW, Wang D, Chong E, Hilger-Rolfe J, Dean JP, Arkenau HT. Ibrutinib combination therapy for advanced gastrointestinal and genitourinary tumours: results from a phase 1b/2 study. BMC Cancer. 2023 Nov 3;23(1):1056. doi: 10.1186/s12885-023-11539-1.
PubMed 37919668
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b/2 Study of Ibrutinib Combination Therapy in Selected Advanced Gastrointestinal and Genitourinary Tumors
- ClinicalTrials.gov ID
- NCT02599324
- Acronym / sponsor ID
- PCYC-1128-CA
- Conditions
- Metastatic Renal Cell Carcinoma, Advanced Urothelial Carcinoma, Advanced Gastric Adenocarcinoma, Metastatic Colorectal Adenocarcinoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 263 participants (actual)
- Lead sponsor
- Pharmacyclics LLC.Industry (pharma, biotech, devices)
- Study start
- 1 Dec 2015 (actual)
- Primary completion
- 20 Aug 2021 (actual)
- Study completion
- 20 Aug 2021 (actual)
- First posted
- 6 Nov 2015 (estimated)
- Results
- Posted 26 Oct 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: Renal Cell Carcinoma (RCC) | Experimental | Drug: ibrutinib, Drug: everolimusPhase 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. |
| Cohort 2: Urothelial Carcinoma (UC) | Experimental | Drug: ibrutinib, Drug: paclitaxelPhase 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. |
| Cohort 3: Gastric Adenocarcinoma (GA or GC) | Experimental | Drug: ibrutinib, Drug: docetaxelPhase 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. |
| Cohort 4: Colorectal Adenocarcinoma (CRC) | Experimental | Drug: ibrutinib, Drug: cetuximabPhase 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. |
| Cohort 5: Urothelial Carcinoma (UC) Ibrutinib | Experimental | Drug: ibrutinibPhase 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. |
| Cohort 6: Urothelial Carcinoma (UC) With Pembrolizumab | Experimental | Drug: ibrutinib, Drug: pembrolizumabPhase 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
- 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
- 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)
Key exclusion criteria (8 listed)
- 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)
- 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
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ibrutinibIbrutinib administered orally once daily with 8 ounces (approximately 240 mL) of water. | Drug | 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 |
| everolimusEverolimus 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. | Drug | Cohort 1: Renal Cell Carcinoma (RCC) |
| paclitaxelPaclitaxel 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. | Drug | Cohort 2: Urothelial Carcinoma (UC) |
| docetaxelDocetaxel 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. | Drug | Cohort 3: Gastric Adenocarcinoma (GA or GC) |
| cetuximabCetuximab 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. | Drug | Cohort 4: Colorectal Adenocarcinoma (CRC) |
| pembrolizumabPembrolizumab 200 mg intravenous (IV) every 3 weeks. | Drug | Cohort 6: Urothelial Carcinoma (UC) With Pembrolizumab |
Primary outcome
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).
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.
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.
15 secondary outcomes
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.
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.
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)
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)
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)
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)
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)
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
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
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
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
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
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
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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37919668Oh DY, Maqueda MA, Quinn DI, O'Dwyer PJ, Chau I, Kim SY, Duran I, Castellano D, Berlin J, Mellado B, Williamson SK, Lee KW, Marti F, Mathew P, Saif MW, Wang D, Chong E, Hilger-Rolfe J, Dean JP, Arkenau HT. Ibrutinib combination therapy for advanced gastrointestinal and genitourinary tumours: results from a phase 1b/2 study. BMC Cancer. 2023 Nov 3;23(1):1056. doi: 10.1186/s12885-023-11539-1.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pharmacyclics LLC study director
Pharmacyclics LLC.
65 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ibrutinib, everolimus and paclitaxel in people with Metastatic Renal Cell Carcinoma and Advanced Urothelial Carcinoma, run by Pharmacyclics LLC. at 65 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 65 sites in United States, South Korea, Spain, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Oct 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02599324, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2023.