Ixazomib Citrate With Gemcitabine Hydrochloride and Doxorubicin Hydrochloride in Treating Patients With Urothelial Cancer That is Metastatic or Cannot Be Removed by Surgery

NCT02420847 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: 2014-0661NCI-2015-00682
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial studies the side effects and best dose of ixazomib citrate, gemcitabine hydrochloride, and doxorubicin hydrochloride when given together in treating patients with urothelial cancer that has spread to other places in the body (metastatic) or cannot be removed by surgery. Ixazomib citrate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as gemcitabine hydrochloride and doxorubicin hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ixazomib citrate together with gemcitabine hydrochloride and doxorubicin hydrochloride may be a better treatment for urothelial cancer.

Conditions

Metastatic Urothelial Carcinoma; Transitional Cell Carcinoma; Unresectable Transitional Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated doses (MTDs) for the combination therapy of ixazomib citrate and gemcitabine hydrochloride/doxorubicin hydrochloride, defined as dose pairs where the target dose limiting toxicity probability is 30% (phase I)

  At 14 days

Secondary Outcomes (1)

• Objective response (phase II extension)

  Up to 2 years

Study Arms (1)

Treatment (ixazomib, gemcitabine, doxorubicin)

EXPERIMENTAL

Patients receive ixazomib citrate PO, gemcitabine hydrochloride IV over 90 minutes, and doxorubicin hydrochloride IV over 15-30 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Drug: Doxorubicin Hydrochloride; Drug: Gemcitabine Hydrochloride; Drug: Ixazomib Citrate

Interventions

Doxorubicin Hydrochloride DRUG

Given IV

Also known as: 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI), ADM, Adriacin, Adriamycin, Adriamycin Hydrochloride, Adriamycin PFS, Adriamycin RDF, ADRIAMYCIN, HYDROCHLORIDE, Adriamycine, Adriblastina, Adriblastine, Adrimedac, Chloridrato de Doxorrubicina, DOX, DOXO-CELL, Doxolem, Doxorubicin HCl, Doxorubicin.HCl, Doxorubin, Farmiblastina, FI 106, FI-106, hydroxydaunorubicin, Rubex

Treatment (ixazomib, gemcitabine, doxorubicin)

Gemcitabine Hydrochloride DRUG

Given IV

Also known as: dFdCyd, Difluorodeoxycytidine Hydrochloride, FF 10832, FF-10832, FF10832, Gemcitabine HCI, Gemzar, LY-188011, LY188011

Treatment (ixazomib, gemcitabine, doxorubicin)

Ixazomib Citrate DRUG

Given PO

Also known as: MLN-9708, MLN9708, Ninlaro

Treatment (ixazomib, gemcitabine, doxorubicin)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 principal investigator (PI), will serve as the final arbiter of eligibility
• 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 upper limit of normal \[ULN\]); 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
• 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
• 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)
• 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
• 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 multigated acquisition scan \[MUGA\], echocardiogram \[ECHO\], stress test, or ventriculography) of at least 45%
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) levels =\< 3 x the upper limit of normal
• Eastern Cooperative Oncology Group (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 (example \[ex\]: perineal pain impacting their ability to sit or ambulate, etc.)
• 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 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
• 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:
• Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR

You may not qualify if:

• 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
• An absolute neutrophil count of \< 1.0 x 10\^9/L
• A calculated creatinine clearance of \< 30 mL/min using Cockcroft Gault or measured by 24 hour urine
• Patient has \>= grade 3 peripheral neuropathy, or grade 2 with pain on clinical examination during the screening period
• Total bilirubin \>= 1.5 x the upper limit of the normal range (ULN)
• Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent
• 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
• 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
• Patients with significant atherosclerotic disease, as defined by:
• Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
• Symptomatic congestive heart failure
• Claudication limiting activity and
• History of cerebrovascular events within the last year (including transient ischemic attack \[TIA\])
• Unstable angina

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

Doxorubicin; Gemcitabine; ixazomib

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Arlene O Siefker-Radtke

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2015
• First Posted: April 20, 2015
• Study Start: July 3, 2015
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: November 10, 2025

Record last verified: 2025-11

Locations

US (1)