Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
Recruitment Status
UNKNOWN
Clinical Phase
PHASE2
Total Enrollment
52 participants
Study Classification
INTERVENTIONAL
Study Start Date
2018-05-04
Study Completion Date
2020-11-30
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Phase II Multicentre, single arm, open label study of Paclitaxel and TAK-228 in metastatic urothelial carcinoma (UC) and the impact of PI3K-mTOR pathway genomic alterations
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Paclitaxel and Pembrolizumab in Treating Patients With Refractory Metastatic Urothelial Cancer
NCT02581982
Transitional Cell Carcinoma
COMPLETED
PHASE2
Nab-Paclitaxel to Paclitaxel in Advanced Urothelial Cancer Progressing on or After Platinum Containing Regimen.
NCT02033993
Urothelial Cancer
COMPLETED
PHASE2
LDK378 Versus Chemotherapy in ALK Rearranged (ALK Positive) Patients Previously Treated With Chemotherapy (Platinum Doublet) and Crizotinib
NCT01828112
Non-Small Cell Lung Cancer
COMPLETED
PHASE3
Phase I-II Study of Intratumoral Urelumab Combined With Nivolumab in Patients With Solid Tumors
NCT03792724
Neoplasms
UNKNOWN
PHASE1/PHASE2
Paclitaxel in Combination With Bevacizumab in Patients With Stage IV NSCLC.
NCT04640935
Non Small Cell Lung Cancer
COMPLETED
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
The PI3K/AKT/mTOR pathway has been shown to be altered in a large percentage of metastatic urothelial carcinoma (UC) tumors. Within this pathway, the PI3 kinase alpha subunit (PIK3CA) is frequently mutated in muscle invasive bladder cancer (MIBC) (15-20%) and PTEN is inactivated in another 30%.
Due to TAK-228's effects on the PI3K/AKT/mTOR pathway in preclinical studies and the frequency of pathway alterations in UC tumors, TAK-228 is a rational therapy for bladder cancer.
This clinical investigation may also reveal how alterations in the PI3K/AKT/mTOR pathway correlate with treatment response. In preclinical bladder cell line models and xenografts done in our lab, synergistic effect has been seen with the combination with paclitaxel.
The primary end-point is objective response rate (ORR) with the goal of increasing the rate from 10% to 26%. Response rates will be measured using RECIST 1.1 criteria. PFS and OS will be measured from the start date of treatment with TAK-228 and paclitaxel. Grade 3, 4 or serious adverse events will be collected and compared to the catalogued events in the phase II trial in breast cancer (NCT01351350). Patient tumors will be analyzed for genetic alterations within the PI3K/AKT/mTOR pathway to determine if alterations within this pathway correlate with response rate, PFS, or OS.
Due to TAK-228's effects on the PI3K/AKT/mTOR pathway in preclinical studies and the frequency of pathway alterations in UC tumors, TAK-228 is a rational therapy for bladder cancer.
This clinical investigation may also reveal how alterations in the PI3K/AKT/mTOR pathway correlate with treatment response. In preclinical bladder cell line models and xenografts done in our lab, synergistic effect has been seen with the combination with paclitaxel.
The primary end-point is objective response rate (ORR) with the goal of increasing the rate from 10% to 26%. Response rates will be measured using RECIST 1.1 criteria. PFS and OS will be measured from the start date of treatment with TAK-228 and paclitaxel. Grade 3, 4 or serious adverse events will be collected and compared to the catalogued events in the phase II trial in breast cancer (NCT01351350). Patient tumors will be analyzed for genetic alterations within the PI3K/AKT/mTOR pathway to determine if alterations within this pathway correlate with response rate, PFS, or OS.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Metastatic Urothelial Cancer
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
Allocation Method
NA
Intervention Model
SINGLE_GROUP
Primary Study Purpose
TREATMENT
Blinding Strategy
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Paclitaxel plus TAK-228
* Paclitaxel will be given on days 1, 8, and 15 of each 28 day cycle intravenously (every Monday or first day of business week if holiday), the day before the first TAK-228 dose. It should be given over approximately one hour.
* TAK-228 will be given orally on Days 2-4, 9-11, 16-18 and 23-25 of each 28-day cycle.
Group Type
EXPERIMENTAL
Paclitaxel and TAK-228
Intervention Type
COMBINATION_PRODUCT
Treatment with TAK-228 oral (D2, 3 and 4 of each week) and paclitaxel (D1 of each week) on Days 1, 8 and 15 for each 28-days cycle until disease progression or unacceptable toxicity. If paclitaxel is stopped, TAK-228 may be continued
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Paclitaxel and TAK-228
Treatment with TAK-228 oral (D2, 3 and 4 of each week) and paclitaxel (D1 of each week) on Days 1, 8 and 15 for each 28-days cycle until disease progression or unacceptable toxicity. If paclitaxel is stopped, TAK-228 may be continued
Intervention Type
COMBINATION_PRODUCT
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
1. Male or female patients 18 years or older.
2. Patients must have a diagnosis of metastatic or advanced histologically confirmed UC (urothelial cancer). Mixed histologies are allowed.
3. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
4. Female patients who:
* Are postmenopausal for at least 1 year before the screening visit, OR
* Are surgically sterile, OR
* If they are of childbearing potential, agree to practice 1 effective method of contraception and 1 additional effective (barrier) method, at the same time, from the time of signing the informed consent through 90 days (or longer as mandated by local labeling \[e.g., USPI, SmPC, etc,\]) after the last dose of study drug, OR
* Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the patient. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, postovulation methods\], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together).
Male patients, even if surgically sterilized (i.e., status post-vasectomy), who:
* Agree to practice highly effective barrier contraception during the entire study treatment period and through 120 days after the last dose of study drug, OR
* Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the patient. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, postovulation methods for the female partner\], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together).
* Agree not to donate sperm during the course of this study or within 120 days after receiving their last dose of study drug
5. Screening clinical laboratory values as specified below:
* Bone marrow reserve consistent with: absolute neutrophil count (ANC) ≥ 1.5 x 109/L; platelet count ≥ 100 x 109/L; hemoglobin ≥ 9 g/dL without transfusion within 1 week preceding study drug administration.
* Hepatic: total bilirubin ≤ 1.5 x upper limit of normal (ULN), transaminases (aspartate aminotransferase/serum glutamic oxaloacetic transaminase-AST/SGOT and alanine aminotransferase/serum glutamic pyruvic transaminase-ALT/SGPT) ≤ 2.5 x ULN (≤ 5 x ULN if liver metastases are present);
* Renal: creatinine clearance ≥50 mL/min based either on Cockroft-Gault estimate or based on urine collection (12 or 24 hour);
* Metabolic: Glycosylated hemoglobin (HbA1c) \<7.0%, fasting serum glucose (≤ 130 mg/dL) and fasting triglycerides ≤ 300 mg/dL.
6. Ability to swallow oral medications.
7. Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
8. Patients who have a history of brain metastasis are eligible for the study provided that all the following criteria are met:
* Brain metastases which have been treated.
* No evidence of disease progression for ≥3 months before the first dose of study drug.
* No hemorrhage after treatment.
* Off-treatment with dexamethasone for 4 weeks before administration of the first dose of TAK-228.
* No ongoing requirement for dexamethasone or anti-epileptic drugs.
9. Patients having received prior systemic chemotherapy treatment for UC, with no limit for number of prior systemic chemotherapeutic or investigational treatment regimens. Specifically, subjects must meet one or more of the following criteria:
• Progression after treatment with a regimen that includes a platinum salt (e.g. - carboplatin or cisplatin) for Stage IV disease.
OR
• Disease recurrence within one years from the date of last dose of chemotherapy or surgery until day the informed consent is signed) after neoadjuvant or adjuvant treatment with a regimen that includes a platinum salt.
10. Measurable disease, as defined by RECIST v.1.1. If all sites of measurable disease have been irradiated, one site must have demonstrated growth after irradiation.
11. Normal (or within 5% of lower limit) left ventricular ejection fraction
2. Patients must have a diagnosis of metastatic or advanced histologically confirmed UC (urothelial cancer). Mixed histologies are allowed.
3. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
4. Female patients who:
* Are postmenopausal for at least 1 year before the screening visit, OR
* Are surgically sterile, OR
* If they are of childbearing potential, agree to practice 1 effective method of contraception and 1 additional effective (barrier) method, at the same time, from the time of signing the informed consent through 90 days (or longer as mandated by local labeling \[e.g., USPI, SmPC, etc,\]) after the last dose of study drug, OR
* Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the patient. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, postovulation methods\], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together).
Male patients, even if surgically sterilized (i.e., status post-vasectomy), who:
* Agree to practice highly effective barrier contraception during the entire study treatment period and through 120 days after the last dose of study drug, OR
* Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the patient. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, postovulation methods for the female partner\], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together).
* Agree not to donate sperm during the course of this study or within 120 days after receiving their last dose of study drug
5. Screening clinical laboratory values as specified below:
* Bone marrow reserve consistent with: absolute neutrophil count (ANC) ≥ 1.5 x 109/L; platelet count ≥ 100 x 109/L; hemoglobin ≥ 9 g/dL without transfusion within 1 week preceding study drug administration.
* Hepatic: total bilirubin ≤ 1.5 x upper limit of normal (ULN), transaminases (aspartate aminotransferase/serum glutamic oxaloacetic transaminase-AST/SGOT and alanine aminotransferase/serum glutamic pyruvic transaminase-ALT/SGPT) ≤ 2.5 x ULN (≤ 5 x ULN if liver metastases are present);
* Renal: creatinine clearance ≥50 mL/min based either on Cockroft-Gault estimate or based on urine collection (12 or 24 hour);
* Metabolic: Glycosylated hemoglobin (HbA1c) \<7.0%, fasting serum glucose (≤ 130 mg/dL) and fasting triglycerides ≤ 300 mg/dL.
6. Ability to swallow oral medications.
7. Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
8. Patients who have a history of brain metastasis are eligible for the study provided that all the following criteria are met:
* Brain metastases which have been treated.
* No evidence of disease progression for ≥3 months before the first dose of study drug.
* No hemorrhage after treatment.
* Off-treatment with dexamethasone for 4 weeks before administration of the first dose of TAK-228.
* No ongoing requirement for dexamethasone or anti-epileptic drugs.
9. Patients having received prior systemic chemotherapy treatment for UC, with no limit for number of prior systemic chemotherapeutic or investigational treatment regimens. Specifically, subjects must meet one or more of the following criteria:
• Progression after treatment with a regimen that includes a platinum salt (e.g. - carboplatin or cisplatin) for Stage IV disease.
OR
• Disease recurrence within one years from the date of last dose of chemotherapy or surgery until day the informed consent is signed) after neoadjuvant or adjuvant treatment with a regimen that includes a platinum salt.
10. Measurable disease, as defined by RECIST v.1.1. If all sites of measurable disease have been irradiated, one site must have demonstrated growth after irradiation.
11. Normal (or within 5% of lower limit) left ventricular ejection fraction
Exclusion Criteria
1. Prior treatment with paclitaxel for UC (in any setting - neoadjuvant, adjuvant or for metastatic disease). Patients treated with prior docetaxel are eligible.
2. Previous treatment with PI3K, AKT, dual PI3K/mTOR inhibitors, TORC1/2 inhibitors or TORC1 inhibitors.
3. Manifestations of malabsorption due to prior gastrointestinal (GI) surgery, GI disease, or for an unknown reason that may alter the absorption of TAK-228. In addition, patients with enteric stomata are also excluded.
5. Presence of central nervous system metastasis, except for those matching requirements detailed per inclusion criterion 8.
6. Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the Investigator's opinion makes it undesirable for the subject to participate in the trial or which would jeopardize compliance with the protocol.
7. History of any of the following within the last 6 months prior to study entry:
* Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures
* Ischemic cerebrovascular event, including TIA and artery revascularization procedures
* Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia)
* Placement of a pacemaker for control of rhythm
* New York Heart Association (NYHA) Class III or IV heart failure (See Appendix C)
* Pulmonary embolism.
8. Significant active cardiovascular or pulmonary disease at the time of study entry, including:
* Uncontrolled high blood pressure (i.e., systolic blood pressure \>180 mm Hg, diastolic blood pressure \> 95 mm Hg). Use of anti-hypertensive agents to control hypertension before Cycle 1 Day 1 is allowed.
* Pulmonary hypertension.
* Uncontrolled asthma or O2 saturation \< 90% by ABG (Arterial Blood Gas) analysis or pulse oximetry on room air.
* Significant valvular disease; severe regurgitation or stenosis by imaging independent of symptom control with medical intervention, or history of valve replacement.
* Medically significant (symptomatic) bradycardia.
* History of arrhythmia requiring an implantable cardiac defibrillator.
* Baseline prolongation of the rate-corrected QT interval (QTc) (e.g., repeated demonstration of QTc interval \> 480 milliseconds, or history of congenital long QT syndrome, or torsades de pointes).
9. History of arrhythmia (multifocal premature ventricular contractions (PVCs), bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation), which is symptomatic or requires treatment (CTCAE grade 3) or asymptomatic sustained ventricular tachycardia.
10. Controlled atrial fibrillation such as with medication or cardioversion is not excluded.
11. Treatment with systemic corticosteroids (either IV or oral steroids, excluding inhalers or low-dose hormone replacement therapy, i.e., prednisone ≤10mg or its equivalent) within 1 week before administration of the first dose of study drug.
12. Women who are currently pregnant or breast feeding.
13. Receipt of any investigational agent, chemotherapy or radiation therapy within 21 days prior to Study Day 1.
14. Any unresolved non-hematologic toxicity greater than CTCAE grade 1 from previous anti-cancer therapy (other than alopecia).
15. Major surgery within 4 weeks, or incompletely healed surgical incision before starting study therapy
16. Grade 2 or greater peripheral neuropathy
17. Diagnosed or treated for another malignancy within 2 years before administration of the first dose of study drug, or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
18. Other clinically significant co-morbidities, such as uncontrolled pulmonary disease, active central nervous system disease, active infection, or any other condition that could compromise the patient's participation in the study.
19. Known human immunodeficiency virus infection
20. Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection.
21. Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol
22. Patients who are taking proton pump inhibitors (PPIs) within 7 days of the first dose of study drug or who require treatment with PPIs throughout the trial or those who are taking H2 receptor antagonists within 24 hours of the first dose of study drug.
2. Previous treatment with PI3K, AKT, dual PI3K/mTOR inhibitors, TORC1/2 inhibitors or TORC1 inhibitors.
3. Manifestations of malabsorption due to prior gastrointestinal (GI) surgery, GI disease, or for an unknown reason that may alter the absorption of TAK-228. In addition, patients with enteric stomata are also excluded.
5. Presence of central nervous system metastasis, except for those matching requirements detailed per inclusion criterion 8.
6. Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the Investigator's opinion makes it undesirable for the subject to participate in the trial or which would jeopardize compliance with the protocol.
7. History of any of the following within the last 6 months prior to study entry:
* Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures
* Ischemic cerebrovascular event, including TIA and artery revascularization procedures
* Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia)
* Placement of a pacemaker for control of rhythm
* New York Heart Association (NYHA) Class III or IV heart failure (See Appendix C)
* Pulmonary embolism.
8. Significant active cardiovascular or pulmonary disease at the time of study entry, including:
* Uncontrolled high blood pressure (i.e., systolic blood pressure \>180 mm Hg, diastolic blood pressure \> 95 mm Hg). Use of anti-hypertensive agents to control hypertension before Cycle 1 Day 1 is allowed.
* Pulmonary hypertension.
* Uncontrolled asthma or O2 saturation \< 90% by ABG (Arterial Blood Gas) analysis or pulse oximetry on room air.
* Significant valvular disease; severe regurgitation or stenosis by imaging independent of symptom control with medical intervention, or history of valve replacement.
* Medically significant (symptomatic) bradycardia.
* History of arrhythmia requiring an implantable cardiac defibrillator.
* Baseline prolongation of the rate-corrected QT interval (QTc) (e.g., repeated demonstration of QTc interval \> 480 milliseconds, or history of congenital long QT syndrome, or torsades de pointes).
9. History of arrhythmia (multifocal premature ventricular contractions (PVCs), bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation), which is symptomatic or requires treatment (CTCAE grade 3) or asymptomatic sustained ventricular tachycardia.
10. Controlled atrial fibrillation such as with medication or cardioversion is not excluded.
11. Treatment with systemic corticosteroids (either IV or oral steroids, excluding inhalers or low-dose hormone replacement therapy, i.e., prednisone ≤10mg or its equivalent) within 1 week before administration of the first dose of study drug.
12. Women who are currently pregnant or breast feeding.
13. Receipt of any investigational agent, chemotherapy or radiation therapy within 21 days prior to Study Day 1.
14. Any unresolved non-hematologic toxicity greater than CTCAE grade 1 from previous anti-cancer therapy (other than alopecia).
15. Major surgery within 4 weeks, or incompletely healed surgical incision before starting study therapy
16. Grade 2 or greater peripheral neuropathy
17. Diagnosed or treated for another malignancy within 2 years before administration of the first dose of study drug, or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
18. Other clinically significant co-morbidities, such as uncontrolled pulmonary disease, active central nervous system disease, active infection, or any other condition that could compromise the patient's participation in the study.
19. Known human immunodeficiency virus infection
20. Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection.
21. Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol
22. Patients who are taking proton pump inhibitors (PPIs) within 7 days of the first dose of study drug or who require treatment with PPIs throughout the trial or those who are taking H2 receptor antagonists within 24 hours of the first dose of study drug.
Minimum Eligible Age
18 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Takeda
INDUSTRY
Sponsor Role
collaborator
Pivotal S.L.
INDUSTRY
Sponsor Role
collaborator
Associació per a la Recerca Oncologica, Spain
OTHER
Sponsor Role
lead
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Responsibility Role
SPONSOR
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Joaquín Bellmunt, MD/PhD
Role: PRINCIPAL_INVESTIGATOR
Hospital del Mar
Alejo Rodríguez-Vida, MD/PhD
Role: PRINCIPAL_INVESTIGATOR
Hospital del Mar
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Hospital General Universitario de Elche
Elche, Alicante, Spain
Site Status
RECRUITING
Parc Taulí Hospital Universitario
Sabadell, Barcelona, Spain
Site Status
RECRUITING
Clínica Universitaria de Navarra
Pamplona, Navarre, Spain
Site Status
RECRUITING
Hospital del Mar
Barcelona, , Spain
Site Status
RECRUITING
Hospital de la Santa Creu i Sant Pau
Barcelona, , Spain
Site Status
RECRUITING
Countries
Review the countries where the study has at least one active or historical site.
Spain
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
References
Explore related publications, articles, or registry entries linked to this study.
Iyer G, Al-Ahmadie H, Schultz N, Hanrahan AJ, Ostrovnaya I, Balar AV, Kim PH, Lin O, Weinhold N, Sander C, Zabor EC, Janakiraman M, Garcia-Grossman IR, Heguy A, Viale A, Bochner BH, Reuter VE, Bajorin DF, Milowsky MI, Taylor BS, Solit DB. Prevalence and co-occurrence of actionable genomic alterations in high-grade bladder cancer. J Clin Oncol. 2013 Sep 1;31(25):3133-40. doi: 10.1200/JCO.2012.46.5740. Epub 2013 Jul 29.
Reference Type
BACKGROUND
Guo Y, Chekaluk Y, Zhang J, Du J, Gray NS, Wu CL, Kwiatkowski DJ. TSC1 involvement in bladder cancer: diverse effects and therapeutic implications. J Pathol. 2013 May;230(1):17-27. doi: 10.1002/path.4176. Epub 2013 Mar 21.
Reference Type
BACKGROUND
Wagle N, Grabiner BC, Van Allen EM, Hodis E, Jacobus S, Supko JG, Stewart M, Choueiri TK, Gandhi L, Cleary JM, Elfiky AA, Taplin ME, Stack EC, Signoretti S, Loda M, Shapiro GI, Sabatini DM, Lander ES, Gabriel SB, Kantoff PW, Garraway LA, Rosenberg JE. Activating mTOR mutations in a patient with an extraordinary response on a phase I trial of everolimus and pazopanib. Cancer Discov. 2014 May;4(5):546-53. doi: 10.1158/2159-8290.CD-13-0353. Epub 2014 Mar 13.
Reference Type
BACKGROUND
Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013 Jan;63(1):11-30. doi: 10.3322/caac.21166. Epub 2013 Jan 17.
Reference Type
BACKGROUND
Ortmann CA, Mazhar D. Second-line systemic therapy for metastatic urothelial carcinoma of the bladder. Future Oncol. 2013 Nov;9(11):1637-51. doi: 10.2217/fon.13.139.
Reference Type
BACKGROUND
Vaughn DJ, Broome CM, Hussain M, Gutheil JC, Markowitz AB. Phase II trial of weekly paclitaxel in patients with previously treated advanced urothelial cancer. J Clin Oncol. 2002 Feb 15;20(4):937-40. doi: 10.1200/JCO.2002.20.4.937.
Reference Type
BACKGROUND
von der Maase H, Sengelov L, Roberts JT, Ricci S, Dogliotti L, Oliver T, Moore MJ, Zimmermann A, Arning M. Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol. 2005 Jul 20;23(21):4602-8. doi: 10.1200/JCO.2005.07.757.
Reference Type
BACKGROUND
Verdoorn BP, Kessler ER, Flaig TW. Targeted therapy in advanced urothelial carcinoma. Oncology (Williston Park). 2013 Mar;27(3):219-26.
Reference Type
BACKGROUND
Ching CB, Hansel DE. Expanding therapeutic targets in bladder cancer: the PI3K/Akt/mTOR pathway. Lab Invest. 2010 Oct;90(10):1406-14. doi: 10.1038/labinvest.2010.133. Epub 2010 Jul 26.
Reference Type
BACKGROUND
Platt FM, Hurst CD, Taylor CF, Gregory WM, Harnden P, Knowles MA. Spectrum of phosphatidylinositol 3-kinase pathway gene alterations in bladder cancer. Clin Cancer Res. 2009 Oct 1;15(19):6008-17. doi: 10.1158/1078-0432.CCR-09-0898. Epub 2009 Sep 29.
Reference Type
BACKGROUND
Bowles DW, Diamond JR, Lam ET, Weekes CD, Astling DP, Anderson RT, Leong S, Gore L, Varella-Garcia M, Vogler BW, Keysar SB, Freas E, Aisner DL, Ren C, Tan AC, Wilhelm F, Maniar M, Eckhardt SG, Messersmith WA, Jimeno A. Phase I study of oral rigosertib (ON 01910.Na), a dual inhibitor of the PI3K and Plk1 pathways, in adult patients with advanced solid malignancies. Clin Cancer Res. 2014 Mar 15;20(6):1656-65. doi: 10.1158/1078-0432.CCR-13-2506. Epub 2014 Feb 3.
Reference Type
BACKGROUND
Bowles DW, Ma WW, Senzer N, Brahmer JR, Adjei AA, Davies M, Lazar AJ, Vo A, Peterson S, Walker L, Hausman D, Rudin CM, Jimeno A. A multicenter phase 1 study of PX-866 in combination with docetaxel in patients with advanced solid tumours. Br J Cancer. 2013 Sep 3;109(5):1085-92. doi: 10.1038/bjc.2013.474. Epub 2013 Aug 13.
Reference Type
BACKGROUND
Gomez-Pinillos A, Ferrari AC. mTOR signaling pathway and mTOR inhibitors in cancer therapy. Hematol Oncol Clin North Am. 2012 Jun;26(3):483-505, vii. doi: 10.1016/j.hoc.2012.02.014. Epub 2012 Mar 31.
Reference Type
BACKGROUND
Seront E, Rottey S, Sautois B, Kerger J, D'Hondt LA, Verschaeve V, Canon JL, Dopchie C, Vandenbulcke JM, Whenham N, Goeminne JC, Clausse M, Verhoeven D, Glorieux P, Branders S, Dupont P, Schoonjans J, Feron O, Machiels JP. Phase II study of everolimus in patients with locally advanced or metastatic transitional cell carcinoma of the urothelial tract: clinical activity, molecular response, and biomarkers. Ann Oncol. 2012 Oct;23(10):2663-2670. doi: 10.1093/annonc/mds057. Epub 2012 Apr 3.
Reference Type
BACKGROUND
Milowsky, M.I., Final results of a multicenter, open-label phase II trial of dovitinib (TKI258) in patients with advanced urothelial carcinoma with either mutated or nonmutated FGFR3. 2013, J Clin Oncol 2013; 31(Suppl 6) [abstract: 255].
Reference Type
BACKGROUND
Bajorin DF. Paclitaxel in the treatment of advanced urothelial cancer. Oncology (Williston Park). 2000 Jan;14(1):43-52, 57; discussion 58, 61-2.
Reference Type
BACKGROUND
Raghavan D. Progress in the chemotherapy of metastatic cancer of the urinary tract. Cancer. 2003 Apr 15;97(8 Suppl):2050-5. doi: 10.1002/cncr.11280.
Reference Type
BACKGROUND
Rossi JF. Phase I study of atacicept in relapsed/refractory multiple myeloma (MM) and Waldenstrom's macroglobulinemia. Clin Lymphoma Myeloma Leuk. 2011 Feb;11(1):136-8. doi: 10.3816/CLML.2011.n.031.
Reference Type
BACKGROUND
Chiang GG, Abraham RT. Targeting the mTOR signaling network in cancer. Trends Mol Med. 2007 Oct;13(10):433-42. doi: 10.1016/j.molmed.2007.08.001. Epub 2007 Oct 1.
Reference Type
BACKGROUND
Sabatini DM. mTOR and cancer: insights into a complex relationship. Nat Rev Cancer. 2006 Sep;6(9):729-34. doi: 10.1038/nrc1974. Epub 2006 Aug 17.
Reference Type
BACKGROUND
Jessen K, Wang S, Kessler L, et al. INK128 is a potent and selective TORC1/2 inhibitor with broad oral antitumor activity. Mol Cancer Ther. 2009;8(12 Suppl) Abstract B148
Reference Type
BACKGROUND
Kessler L, Wang S, Xin G, Kucharski J, Staunton J, Lan L, et al. INK128, an orally active TORC1/2 kinase inhibitor, shows broad antitumor activity and enhances efficacy of cytotoxic as well as targeted agents. Cancer Res 2010;70(8; Supplement 1 Abstract 4496).
Reference Type
BACKGROUND
Hassan B, Akcakanat A, Takafumi S, Evans K, Adkins F, Meric-Bernstam F. Inhibitor MLN0128 Has Antitumor Efficacy In Cell Lines With Intrinsic And Acquired Rapamycin-Resistance. Academic Surgical Congress 2013(Abstract ASC20130420).
Reference Type
BACKGROUND
Shafer A, Zhou C, Gehrig PA, Boggess JF, Bae-Jump VL. Rapamycin potentiates the effects of paclitaxel in endometrial cancer cells through inhibition of cell proliferation and induction of apoptosis. Int J Cancer. 2010 Mar 1;126(5):1144-54. doi: 10.1002/ijc.24837.
Reference Type
BACKGROUND
Shu CH, Yang WK, Shih YL, Kuo ML, Huang TS. Cell cycle G2/M arrest and activation of cyclin-dependent kinases associated with low-dose paclitaxel-induced sub-G1 apoptosis. Apoptosis. 1997;2(5):463-70. doi: 10.1023/a:1026422111457.
Reference Type
BACKGROUND
Mondesire WH, Jian W, Zhang H, Ensor J, Hung MC, Mills GB, Meric-Bernstam F. Targeting mammalian target of rapamycin synergistically enhances chemotherapy-induced cytotoxicity in breast cancer cells. Clin Cancer Res. 2004 Oct 15;10(20):7031-42. doi: 10.1158/1078-0432.CCR-04-0361.
Reference Type
BACKGROUND
Voss M, Gordon MS, Mita M, Rini B, Makker V, Macarulla T, et al. Phase I study of investigational oral mTORC1/2 inhibitor TAK-228 (formerly MLN0128): expansion phase in patients with renal, endometrial, or bladder cancer. ESMO poster Sept 2015
Reference Type
BACKGROUND
Ghobrial IM, Siegel DS, Vij R, Berdeja JG, Richardson PG, Neuwirth R, Patel CG, Zohren F, Wolf JL. TAK-228 (formerly MLN0128), an investigational oral dual TORC1/2 inhibitor: A phase I dose escalation study in patients with relapsed or refractory multiple myeloma, non-Hodgkin lymphoma, or Waldenstrom's macroglobulinemia. Am J Hematol. 2016 Jun;91(4):400-5. doi: 10.1002/ajh.24300.
Reference Type
BACKGROUND
TAK-228 Investigator Brochure Edition 10. 22 March 2017
Reference Type
BACKGROUND
PACLITAXEL - paclitaxel injection, solution [package insert]. Princeton, NJ. Sandoz; 2011
Reference Type
BACKGROUND
Hernandez-Prat A, Rodriguez-Vida A, Juanpere-Rodero N, Arpi O, Menendez S, Soria-Jimenez L, Martinez A, Iarchouk N, Rojo F, Albanell J, Brake R, Rovira A, Bellmunt J. Novel Oral mTORC1/2 Inhibitor TAK-228 Has Synergistic Antitumor Effects When Combined with Paclitaxel or PI3Kalpha Inhibitor TAK-117 in Preclinical Bladder Cancer Models. Mol Cancer Res. 2019 Sep;17(9):1931-1944. doi: 10.1158/1541-7786.MCR-18-0923. Epub 2019 Jun 3.
Reference Type
DERIVED
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
2017-004486-27
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
X31005
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.
Biweekly Gemcitabine and Docetaxel as First Line Treatment for Advanced Disease in Elderly Non-Small Cell Lung Cancer (NSCLC) Patients
NCT00905983
UNKNOWN
PHASE2
A Phase 2 Study Evaluating ABT-751 in Combination With Taxotere in Advanced Non-Small Cell Lung Cancer
NCT00354562
TERMINATED
PHASE1/PHASE2
CAB-AXL-ADC Safety and Efficacy Study in Adults With NSCLC
NCT04681131
COMPLETED
PHASE2
Efficacity of Weekly Paclitaxel in Association or Not With Bevacizumab in Metastatic or Locally Advanced Angiosarcomas
NCT01303497
COMPLETED
PHASE2
Safety and Efficacy Study of Abraxane in Combination With Carboplatin to Treat Advanced NSCL Cancer in the Elderly
NCT02151149
COMPLETED
PHASE4
Paclitaxel-Avelumab for Angiosarcoma
NCT03512834
UNKNOWN
PHASE2
A Study of Ramucirumab (LY3009806) Plus Docetaxel in Participants With Urothelial Cancer
NCT02426125
COMPLETED
PHASE3
Docetaxel With or Without TAK-117 (MLN1117) in Participants With Locally Advanced or Metastatic Non-small Cell Lung Cancer
NCT02393209
TERMINATED
PHASE1/PHASE2
Chemoradiotherapy in Stage III Non-small Cell Lung Cancer (NSCLC)
NCT01102231
COMPLETED
PHASE2
Paclitaxel, Carboplatin, and Radiation Therapy With or Without Adjuvant Paclitaxel and Carboplatin in Treating Patients With Stage II or Stage III Unresectable Non-Small Cell Lung Cancer
NCT00077220
UNKNOWN
PHASE3
A Study Evaluating Platinum-Pemetrexed-Atezolizumab (+/-Bevacizumab) for Patients With Stage IIIB/IV Non-squamous Non-small Cell Lung Cancer With EGFR Mutations, ALK Rearrangement or ROS1 Fusion Progressing After Targeted Therapies
NCT04042558
COMPLETED
PHASE2
Broncho-Adventitial Delivery of Paclitaxel to Extend Airway Patency in Malignant Airway Obstruction Patients
NCT02066103
COMPLETED
NA
Paclitaxel in Treating Patients With Lung Cancer
NCT00002972
COMPLETED
PHASE2
LDK378 Versus Chemotherapy in Previously Untreated Patients With ALK Rearranged Non-small Cell Lung Cancer
NCT01828099
COMPLETED
PHASE3
Study of Avelumab and Cetuximab Plus Gemcitabine and Cisplatin in Participants With NSCLC
NCT03717155
COMPLETED
PHASE2
Paclitaxel in Treating Older Patients With Solid Tumors
NCT00003092
COMPLETED
PHASE3
Bempegaldesleukin and Pembrolizumab With or Without Chemotherapy in Locally Advanced or Metastatic Solid Tumors
NCT03138889
TERMINATED
PHASE1/PHASE2
Phase 1b/2a, Open-label Study of Vactosertib in Combination With Durvalumab in Advanced NSCLC
NCT03732274
COMPLETED
PHASE1/PHASE2
CPI-613 and Docetaxel in Treating Patients With Stage IIIB or IV Non-small Cell Lung Cancer
NCT03370159
WITHDRAWN
PHASE1/PHASE2
Carboplatin and Paclitaxel Albumin-Stabilized Nanoparticle Formulation Followed by Radiation Therapy and Erlotinib in Treating Patients With Stage III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery
NCT00553462
COMPLETED
PHASE2
Study of Pazopanib and Paclitaxel in Advanced Non-small Cell Lung Cancer
NCT00866528
COMPLETED
PHASE1
A Study of Atezolizumab in Combination With Carboplatin + Paclitaxel or Carboplatin + Nab-Paclitaxel Compared With Carboplatin + Nab-Paclitaxel in Participants With Stage IV Squamous Non-Small Cell Lung Cancer (NSCLC) [IMpower131]
NCT02367794
COMPLETED
PHASE3
Paclitaxel in Treating Patients With Locally Advanced or Metastatic Soft Tissue Angiosarcoma or Lymphangiosarcoma That Cannot Be Removed By Surgery
NCT00217607
COMPLETED
PHASE2
Study of Paclitaxel, Carboplatin, and Cetuximab for Advanced Lung Cancer
NCT00315185
COMPLETED
PHASE2
Study of CP-751,871 in Combination With Carboplatin and Paclitaxel in Advanced Lung Cancer
NCT00603538
COMPLETED
PHASE1