Houston, Texas 77030


Purpose:

This clinical research study is made up of 2 phases. The goal of Phase 1 of this study is to learn the highest tolerated dose of the combination of ixazomib, gemcitabine, and doxorubicin that can be given to patients with urothelial cancer. The goal of Phase 2 of this study is to learn if the combination of ixazomib, gemcitabine, and doxorubicin can help to control urothelial cancer. The safety of the drug combinations will be studied in both phases. This is an investigational study. Ixazomib is not FDA approved or commercially available for the treatment of urothelial cancer. Gemcitabine and doxorubicin are FDA approved and commercially available for several other types of cancer. Their use in combination with ixazomib in urothelial cancer is investigational. The study doctor can explain how the study drugs are designed to work. Up to 57 participants will be enrolled in this study. All will take part at MD Anderson.


Study summary:

Study Groups: If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you join this study. Up to 6 groups of up to 4 participants will be enrolled in Phase 1 of the study, and up to 33 participants will be enrolled in Phase 2. If you are enrolled in Phase 1, the combination dose of ixazomib, gemcitabine, and doxorubicin you receive will depend on when you join this study. The first group of participants will receive the lowest combination dose level. Each new group will receive a higher dose of the drug combination than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of the drug combination is found. If you are enrolled in Phase 2, you will receive the drug combination at the highest dose that was tolerated in Phase 1. Study Drug Administration: On Day 1 of every 14-day cycle, you will take ixazomib 1 time by mouth, receive gemcitabine by vein over about 90 minutes, and receive doxorubicin by vein over 15-30 minutes. Gemcitabine and doxorubicin may be given through a catheter. A catheter is a sterile flexible tube that will be placed into a large vein while you are under anesthesia. Your doctor will explain this procedure to you in more detail, and you will be required to sign a separate consent form. You should not chew, break, or open the capsules of ixazomib. If the capsules break, be careful not to spread their dust while cleaning it up. The product may be harmful to breathe in, swallow, or touch. Gloves and protective clothing should be worn during cleanup and return of broken capsules and powder to minimize skin contact. The area should be ventilated and the site washed with soap and water after material pick-up is complete. The material should be disposed of as hazardous medical waste in compliance with federal, state, and local regulations. In case of contact with the powder (such as from a broken capsule), skin should be washed right away with soap and large amounts of water for at least 15 minutes. In case of contact with the eyes, large amounts of water should be used to flush the eyes for at least 15 minutes. Call the study staff right away if this happens. Study Visits: On Day 1 of each cycle: - You will have a physical exam. - Blood (about 3-4 tablespoons) will be drawn for routine tests. - Every 3 cycles starting with Cycle 4 (Cycles 4, 7, 10, and so on), you will also have an x-ray and CT scans or MRIs to check the status of the disease. On Day 8 of Cycles 1 and 2, blood (about 3-4 tablespoons) will be drawn for routine tests. If the disease gets worse, you will have either an ECHO or MUGA scan to check your heart function, if your doctor thinks it is needed. At any time that the doctor thinks it is needed, you will have a bone scan to check the status of the disease. Length of Treatment: You may continue receiving the study drugs for as long as the doctor thinks it is in your best interest. You may no longer be able to take the study drugs if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.


Criteria:

Inclusion Criteria: 1. All patients must have histologic demonstration of metastatic or locally unresectable transitional cell carcinoma of the urothelium. Variant histology is allowed as long as there is an urothelial component present. The PI will serve as the final arbiter of eligibility. 2. All patients must have measurable or evaluable disease. In general, liver and lung lesions should be at least 1 cm, and patients with node-only disease should have lesions of >/= 1.5 cm in greatest dimension. Patients with disease confined to bone may be eligible if a measurable lytic defect is present or a serum marker is elevated (>4 x ULN). The Principal Investigator is the final arbiter in questions related to measurability. Patients with a three-dimensional mass or pelvic sidewall fixation on bladder examination under anesthesia are considered to have measurable disease. 3. Patients must have had at least one prior therapy to be eligible for either phase I or II, unless they are either not candidates for or refuse cisplatin-based therapy. 4. Phase I: Patients are eligible with any number of prior regimens regardless of what those regimens contained (i.e. prior Bortezomib or combination gemcitabine and adriamycin is acceptable). 5. Phase II: patients are eligible if their previous chemotherapy regimen did not contain bortezomib, carfilzomib, or other known proteasome inhibitor or a combination of gemcitabine >/= 800 mg/m^2 plus adriamycin >/= 30 mg/m^2. Patients who receive sequential or alternating therapy as part of front-line treatment will be counted as having one prior regimen. Patients who have failed prior neoadjuvant chemotherapy will be eligible for this trial. 6. If prior history of ischemic heart disease or exposure to 200 mg/m^2 of doxorubicin, patients must have a measured ejection fraction (either by MUGA, ECHO, stress test, or ventriculography) of at least 45%. 7. Have preserved hepatic function as shown by alanine aminotransferase (ALT) and AST (SGOT) levels </= 3 x the upper limit of normal. 8. ECOG performance status (PS) </= 2. Patients with a PS of 3 are eligible if the performance status is due to their malignancy, and not a co-morbid medical condition (ex: perineal pain impacting their ability to sit or ambulate, etc.) 9. Male or Female patients 18 years or older who: a) Are postmenopausal for at least 1 year before the screening visit, OR; b) Are surgically sterile, OR; c) If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug, OR ; d) Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.); Male patients, even if surgically sterilized (ie, status post-vasectomy), must agree to one of the following: e) Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR; 10. (Cont. #9) f) Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.) 11. 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. Exclusion Criteria: 1. Platelet count of < 100 x 10^9/L. Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment. 2. An absolute neutrophil count of < 1.0 x 10^9/L. 3. A calculated creatinine clearance of < 30 mL/min using Cockcroft Gault or measured by 24 hour urine 4. Patient has >/= Grade 3 peripheral neuropathy, or Grade 2 with pain on clinical examination during the screening period. 5. Total bilirubin >/= 1.5 x the upper limit of the normal range (ULN). 6. Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent. 7. Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test (Unless there is reasonable certainty that beta-hCG is coming from the tumor). Pregnancy testing is not required for post-menopausal or surgically sterilized women. 8. Participation in other clinical trials with investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this trial. 9. Patients with significant atherosclerotic disease, as defined by: a) Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure (See Appendix 5) uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.; b) Symptomatic congestive heart failure.; c) Claudication limiting activity and ; d) History of cerebrovascular events within the last year (including TIA).; e) Unstable angina. 10. Patients with known active brain metastases. [Subjects with previously treated brain metastases are eligible provided they are stable (defined as without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment) and neurologic symptoms have returned to baseline.] 11. Radiotherapy within 28 days before enrollment. If the involved field is small, 14 days will be considered a sufficient interval between treatment and administration of the therapy. 12. Diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with pathologically confirmed completely resected prostate cancer no higher than stage pT2a and no biochemical relapse, or pT2c tumors involving less than 5% of the prostate and no biochemical relapse, nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection. 13. Systemic treatment, within 14 days before the first dose of ixazomib, with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of CYP3A (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort. 14. Failure to have fully recovered (ie, </= Grade 1 toxicity) from the reversible effects of prior chemotherapy. 15. Major surgery within 14 days before enrollment. The PI will serve as the final arbiter as to what constitutes major surgery. 16. Infection requiring current intravenous antibiotic therapy. The PI will serve as the final arbiter regarding eligibility. 17. Ongoing or active systemic infection with the following: known active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive. 18. Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol. 19. Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing. Patients who have had cystectomy with conduit, neobladder, or pouch using a portion of their terminal ileum are allowed if, the patient is stable without clinically significant metabolic disturbances OR stoma- and/or anastomosis-related complications OR post-surgical gut abnormalities that would compromise drug absorption. 20. Patient has >/= Grade 3 peripheral neuropathy, or Grade 2 with pain on clinical examination during the screening period.


NCT ID:

NCT02420847


Primary Contact:

Principal Investigator
Arlene Siefker-Radtke, MD
M.D. Anderson Cancer Center

Arlene Siefker-Radtke, MD
Phone: 713-792-2830


Backup Contact:

N/A


Location Contact:

Houston, Texas 77030
United States



There is no listed contact information for this specific location.

Site Status: Recruiting


Data Source: ClinicalTrials.gov

Date Processed: November 22, 2017

Modifications to this listing: Only selected fields are shown, please use the link below to view all information about this clinical trial.


Click to view Full Listing

This study is not currently recruiting Study Participants on ClinicalConnection.com. The form below is not enabled.